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Sample records for arterial hypertension due

  1. Hypertension due to renal artery stenosis in transplanted kidneys.

    PubMed Central

    Lindsey, E S; Garbus, S B; Golladay, E S; McDonald, J C

    1975-01-01

    Hypertension appeared to be related to stenosis of the hypogastricrenal artery system in 5 patients among 153 recipients of renal allografts. Renin assay and arteriography were crucial in the comprehensive evaluation of patients whose hypertension was not clearly related to rejection or excessive sodium intake. Hypereninemia was persistent in 4 of the 5 patients. Stenoses of the transplant renal arteries in three patients were caused by extensive intimal plaque formation. In one patient, periarterial fibrosis caused reduction of flow; 180 degrees torsion of the anastomosis resulted in stenosis in the fifth patient. Surgical correction is difficult and may be facilitated by a transabdominal approach. Vein bypass is probably preferable to patch angioplasty for intimal lesions. Following operation, hypertension was ameliorated and function improved in all patients. Rejection, which has been suggested as one of the causes of intimal plaque formation, ultimately led to the loss of the transplant in one patient. Function is normal in two patients; two patients have evidence of chronic rejection. No effort should be spared to evaluate this special group of patients whose transplant function can predictably be prolonged by decisive surgical management. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. PMID:1093491

  2. Curcumin nanoparticles attenuate cardiac remodeling due to pulmonary arterial hypertension.

    PubMed

    Rice, Kevin M; Manne, Nandini D P K; Kolli, Madhukar B; Wehner, Paulette S; Dornon, Lucy; Arvapalli, Ravikumar; Selvaraj, Vellaisamy; Kumar, Arun; Blough, Eric R

    2016-12-01

    Herein, we investigate whether curcumin nanoparticles (Cur NPs) are effective for the treatment of monocrotaline (MCT)-induced pulmonary arterial hypertension in Sprague Dawley rat. Echocardiography was performed at the start of the study and 28 days after MCT injection. Compared to MCT only animals, Cur NP administration was associated with reduced right ventricular (RV) wall thickness and a decreased right ventricle weight/body weight ratio. Cur NPs also attenuated MCT induced increase in RV mRNA expression of TNF-α and IL-1β. These changes were also associated with decreased RV expression of nitrotyrosine, fibronectin and myosin heavy chain-β.

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

    PubMed Central

    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 for 10% and <5% of cases, respectively. The prevalence of FMD in the general population is not well known. Estimates are derived from screening kidney donors, with a prevalence of about 2.6%. Among patients with renovascular hypertension (RVH), its incidence is about 10%, whereas 80-90% of RVH is due to atherosclerotic renal artery stenosis (ARAS). The treatment of choice of hypertension due to FMD is percutaneous renal angioplasty (PTRA). In contrast, hypertension due to ARAS is not frequently responsive to PTRA. In order to achieve successful control of hypertension in patients with FMD, a combination of PTRA with drugs that block the renin-angiotensin-aldosterone system (RAAS) is often necessary. The purpose of this review was to search the literature for newer diagnostic methods and treatment of FMD. Therefore, a Medline search of the English literature of published papers between 2008 and December 2013 was performed. Of 58 papers reviewed, 19 pertinent papers were selected including, studies, reviews, registries and case reports. The information from these studies together with collateral literature will be discussed in this concise review. PMID:24649423

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

    PubMed

    Chrysant, Steven G; Chrysant, George S

    2014-02-01

    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 for 10% and <5% of cases, respectively. The prevalence of FMD in the general population is not well known. Estimates are derived from screening kidney donors, with a prevalence of about 2.6%. Among patients with renovascular hypertension (RVH), its incidence is about 10%, whereas 80-90% of RVH is due to atherosclerotic renal artery stenosis (ARAS). The treatment of choice of hypertension due to FMD is percutaneous renal angioplasty (PTRA). In contrast, hypertension due to ARAS is not frequently responsive to PTRA. In order to achieve successful control of hypertension in patients with FMD, a combination of PTRA with drugs that block the renin-angiotensin-aldosterone system (RAAS) is often necessary. The purpose of this review was to search the literature for newer diagnostic methods and treatment of FMD. Therefore, a Medline search of the English literature of published papers between 2008 and December 2013 was performed. Of 58 papers reviewed, 19 pertinent papers were selected including, studies, reviews, registries and case reports. The information from these studies together with collateral literature will be discussed in this concise review.

  5. Peritoneal ultrafiltration for refractory fluid overload and ascites due to pulmonary arterial hypertension.

    PubMed

    Husain-Syed, Faeq; Muciño-Bermejo, María-Jimena; Ronco, Claudio; Seeger, Werner; Birk, Horst-Walter

    2015-01-01

    Pulmonary hypertension is a common finding in patients with advanced liver disease. Similarly, among patients with advanced pulmonary arterial hypertension, right heart failure leads to congestive hepatopathy. Diuretic resistant fluid overload in both advanced pulmonary hypertension and chronic liver disease is a demanding challenge for physicians. Venous congestion and ascites-induced increased intra-abdominal pressure are essential regarding recurrent hospitalization, morbidity and mortality. Due to impaired right-ventricular function, many patients cannot tolerate extracorporeal ultrafiltration. Peritoneal dialysis, a well-established, hemodynamically tolerated treatment for outpatients may be a good alternative to control fluid status. We present a patient with pulmonary arterial hypertension and congestive hepatopathy hospitalized for over 3 months due to ascites induced refractory volume overload treated with peritoneal ultrafiltration. We report the treatment benefits on fluid balance, cardiorenal and pulmonary function, as well as its safety. In conclusion, we report a case in which peritoneal ultrafiltration was an efficient treatment option for refractory ascites in patients with congestive hepatopathy.

  6. Left main bronchus compression due to main pulmonary artery dilatation in pulmonary hypertension: two case reports.

    PubMed

    Jaijee, Shareen K; Ariff, Ben; Howard, Luke; O'Regan, Declan P; Gin-Sing, Wendy; Davies, Rachel; Gibbs, J Simon R

    2015-12-01

    Pulmonary arterial dilatation associated with pulmonary hypertension may result in significant compression of local structures. Left main coronary artery and left recurrent laryngeal nerve compression have been described. Tracheobronchial compression from pulmonary arterial dilatation is rare in adults, and there are no reports in the literature of its occurrence in idiopathic pulmonary arterial hypertension. Compression in infants with congenital heart disease has been well described. We report 2 cases of tracheobronchial compression: first, an adult patient with idiopathic pulmonary arterial hypertension who presents with symptomatic left main bronchus compression, and second, an adult patient with Eisenmenger ventricular septal defect and right-sided aortic arch, with progressive intermedius and right middle lobe bronchi compression in association with enlarged pulmonary arteries.

  7. Regression of pulmonary artery hypertension due to development of a pulmonary arteriovenous malformation.

    PubMed

    Hasan, Ashfaq; Sastry, B K S; Aleem, M A; Reddy, Gokul; Mahmood, Syed

    2014-01-01

    Idiopathic Pulmonary Hypertension (IPAH) is characterized by elevated pulmonary arterial pressure in the absence of an identifiable underlying cause. The condition is usually relentlessly progressive with a short survival in the absence of treatment.(1) We describe a patient of IPAH in whom the pulmonary artery pressures significantly abated with complete disappearance of symptoms, following spontaneous development of a pulmonary arterio-venous malformation (PAVM). Copyright © 2014 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2016-01-01

    Background Although pulmonary hypertension due to left heart disease (LHD-PH) accounts for the largest proportion of pulmonary hypertension, few reports on the epidemiological analysis of LHD-PH exist. Recently, pulmonary arterial capacitance (PAC) has attracted attention as a possible factor of right ventricular afterload along with pulmonary vascular resistance. We therefore investigated the clinical significance of PAC in LHD-PH. Methods The subject consisted of 252 LHD-PH patients (145 men, mean age 63.4 ± 14.7 years) diagnosed by right heart catheterization. PAC was estimated by the ratio between stroke volume and pulmonary arterial pulse pressure. Patients were classified into four groups according to the PAC (1st quartile was 0.74 to 1.76 ml/mmHg, the 2nd quartile 1.77 to 2.53 ml/mmHg, the 3rd quartile 2.54 to 3.59 ml/mmHg, and the 4th quartile 3.61 to 12.14 ml/mmHg). The end-points were defined as rehospitalization due to worsening heart failure and/or cardiac death. The Cox proportional hazard regression model was used to determine what variables were associated with cardiac events. Results The patients in the 1st quartile had the lowest cardiac index and stroke volume index, and the highest mean pulmonary arterial pressure, mean pulmonary capillary wedge pressure, and pulmonary vascular resistance compared with the 2nd, 3rd, and 4th quartiles. Fifty-four patients experienced cardiac events during the follow-up period (median 943 days). The event-free rate of the 1st quartile was significantly lower than that of the 3rd and 4th quartiles (66.7% vs 82.5% [3rd quartile], P = 0.008; and 92.1% [4th quartile], P < 0.001). The Cox hazard analysis revealed that PAC was significantly associated with cardiac events (HR 0.556, 95% CI 0.424–0.730, P < 0.001). Conclusion PAC is useful in the prediction of cardiac event risk in LHD-PH patients. PMID:27875533

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

    PubMed

    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.

  10. Arterial hypertension due to fructose ingestion: model based on intermittent osmotic fluid trapping in the small bowel

    PubMed Central

    2010-01-01

    Based on recently reported data that fructose ingestion is linked to arterial hypertension, a model of regulatory loops involving the colon role in maintenance of fluid and sodium homeostasis is proposed. In normal digestion of hyperosmolar fluids, also in cases of postprandial hypotension and in patients having the "dumping" syndrome after gastric surgery, any hyperosmolar intestinal content is diluted by water taken from circulation and being trapped in the bowel until reabsorption. High fructose corn sirup (HFCS) soft drinks are among common hyperosmolar drinks. Fructose is slowly absorbed through passive carrier-mediated facilitated diffusion, along the entire small bowel, thus preventing absorption of the trapped water for several hours. Here presented interpretation is that ingestion of hyperosmolar HFCS drinks due to a transient fluid shift into the small bowel increases renin secretion and sympathetic activity, leading to rise in ADH and aldosterone secretions. Their actions spare water and sodium in the large bowel and kidneys. Alteration of colon absorption due to hormone exposure depends on cell renewal and takes days to develop, so the momentary capacity of sodium absorption in the colon depends on the average aldosterone and ADH exposure during few previous days. This inertia in modulation of the colon function can make an individual that often takes HFCS drinks prone to sodium retention, until a new balance is reached with an expanded ECF pool and arterial hypertension. In individuals with impaired fructose absorption, even a higher risk of arterial hypertension can be expected. PMID:20579372

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

    PubMed

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

    2017-08-01

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

  12. Splenic Arterial Embolization in the Treatment of Severe Portal Hypertension Due to Pancreatic Diseases: The Primary Experience in 14 Patients

    SciTech Connect

    Wang, Qi Xiong, Bin Zheng, ChuanSheng Liang, Ming Han, Ping

    2016-03-15

    ObjectiveThis retrospective study reports our experience using splenic arterial particle embolization and coil embolization for the treatment of sinistral portal hypertension (SPH) in patients with and without gastric bleeding.MethodsFrom August 2009 to May 2012, 14 patients with SPH due to pancreatic disease were diagnosed and treated with splenic arterial embolization. Two different embolization strategies were applied; either combined distal splenic bed particle embolization and proximal splenic artery coil embolization in the same procedure for acute hemorrhage (1-step) or interval staged distal embolization and proximal embolization in the stable patient (2-step). The patients were clinically followed.ResultsIn 14 patients, splenic arterial embolization was successful. The one-step method was performed in three patients suffering from massive gastric bleeding, and the bleeding was relieved after embolization. The two-step method was used in 11 patients, who had chronic gastric variceal bleeding or gastric varices only. The gastric varices disappeared in the enhanced CT scan and the patients had no gastric bleeding during follow-up.ConclusionsSplenic arterial embolization, particularly the two-step method, proved feasible and effective for the treatment of SPH patients with gastric varices or gastric variceal bleeding.

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

    PubMed

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

    2015-12-01

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

  14. Pulmonary arterial hypertension

    PubMed Central

    2013-01-01

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

  15. Pulmonary arterial hypertension.

    PubMed

    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

    2013-07-06

    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

  16. Pulmonary hypertension due to a pulmonary artery leiomyosarcoma: A case report

    PubMed Central

    Adeli, Hassan; Nemati, Bardia; Jandaghi, Mahboubeh; Riahi, Mohammad Mahdi; Salarvand, Fatemeh

    2014-01-01

    BACKGROUND Primary pulmonary artery sarcomas are very rare and their histologic type called leiomyosarcoma is even rarer. These tumors are frequently misdiagnosed as pulmonary thromboembolism in clinical settings. Many patients receive anticoagulant therapy without response, and many are diagnosed postmortem only. Most of the tumors reported in the literature have involved the right ventricular outflow tract and the main pulmonary trunk, often extending into the main pulmonary artery (MPA) branches. CASE REPORT A 64-year-old woman presented with weakness, fatigue, malaise, dyspnea, and marked elevation of pulmonary artery pressure was admitted to our hospital. She was initially diagnosed with chronic pulmonary thromboembolism, and chest computed tomography (CT) scan revealed lobulated heterogeneous left hilar mass extended to precarinal and subcarinal space. Magnetic resonance imaging (MRI) demonstrated a polypoid lesion at the trunk with extension to left MPA and its first branch. The patient was operated, and a yellowish-shiny solid mass in pulmonary trunk was seen intra-operation and pulmonary endarterectomy was performed. Her tumor was pathologically diagnosed as pulmonary artery leiomyosarcoma. CONCLUSION Clinicians must consider pulmonary artery sarcoma when making the differential diagnosis for patients with pulmonary artery masses. The clinical prediction scores and the CT and MRI findings can help identifying patients with pulmonary artery sarcoma. PMID:25161682

  17. [Definition of arterial hypertension].

    PubMed

    Degaute, J P

    1994-01-01

    Recent publication of several consensus by well-known international experts in the field of high blood pressure gives us the opportunity to update the definition of hypertension. For the first time, systolic blood pressure is taken into account to define hypertensives. Ambulatory blood pressure monitoring has been recently developed for the evaluation and treatment of hypertensive patients. Due to the absence of world-wide recognized normative data and the lack of prospective studies assessing the superiority of ambulatory blood pressure monitoring over casual blood pressure measurement for the prediction of cardiovascular events, the use of this new technique is to be restricted to a limited number of hypertensive patients.

  18. Capsaicin and arterial hypertensive crisis.

    PubMed

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

    2010-10-08

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

  19. [Renovascular hypertension due to unilateral renal artery stenosis with hypokalemic alkalosis, the salt-losing syndrome and reversible hyperechogenicity of the contralateral kidney. A study of 2 infants].

    PubMed

    Castelló Girona, F; Yeste Fernández, D; Porta Ribera, R; Enríquez Cívicos, G

    1996-07-01

    This report describes two infants with severe arterial hypertension secondary to unilateral renal artery stenosis which was manifested by polyuria, polydipsia, hypokalemic alkalosis, hyponatremia, increased natriuresis and increased plasma values of rennin and aldosterone. On sonographic examination, the contralateral non-stenotic kidney of both patients appeared enlarged and hyperechogenic mimicking parenchymal lesion. When the patients became normotensive, their sodium and potassium balance became normal and their contralateral non-stenotic kidney also became normal in size and echogenicity. The increase of the filtration and the natriuresis observed in the contralateral non-stenotic kidney of the patients with renovascular hypertension due to renal artery stenosis might be responsible for the hyperechogenicity. When the patients became normotensive, the filtration and excretion of sodium of the contralateral kidney also became normal and the increase of echogenicity also disappeared. The reversibility of the sonographic findings suggest a functional origin.

  20. [Arterial hypertension secondary to endocrine disorders].

    PubMed

    Minder, Anna; Zulewski, Henryk

    2015-06-01

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

  1. Update in pulmonary arterial hypertension.

    PubMed

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

    2016-11-01

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

  2. A review of pulmonary arterial hypertension

    PubMed Central

    Gan, C.T.; Noordegraaf, A. Vonk; Marques, K.M.J.; Bronzwaer, J.G.F.; Postmus, P.E.; Boonstra, A.

    2004-01-01

    Pulmonary arterial hypertension (PAH) is a disease characterised by an increased pulmonary artery pressure. The precapillary pulmonary arteries show distinct pathobiological changes, i.e. medial hypertrophy, intimal fibrosis, microthrombi and plexiform lesions. Although the pathogenesis is not completely understood, pulmonary vascular proliferation and remodelling, due to a variety of mediators, is believed to play the pathogenetic key role. Genetic research reveals molecular deformities and gene mutations associated with phenotypic PAH. This article covers novel insights into pathobiology, pathogenesis and genes of PAH, which led to a novel classification system and a diagnostic work-up, emanated from the World Health Organisation Symposium on Pulmonary Hypertension in Venice in June 2003. PMID:25696347

  3. Anticoagulation in Pulmonary Arterial Hypertension.

    PubMed

    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.

  4. Pulmonary hypertension due to left heart disease.

    PubMed

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

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

  5. [Unstable hypertension due to renal artery compression by the developed diaphragm in a 17-year-old athlete: a case report].

    PubMed

    Maeda, Sayako; Yamamoto, Shinya; Makiishi, Tetsuya

    2011-01-01

    A 17-year-old high school boy was admitted to our hospital because of hypertension. Doppler ultrasound of the renal arteries and 3D-CT angiography showed a stenosis of the right renal artery, which was pushed against the aorta by the right crus of the diaphragm. He underwent aortography and selective renal arteriography. His right renal artery originated from the aorta at a higher level than the left renal artery, between the celiac artery and the superior mesenteric artery. Renal arteriography confirmed a 50% reduction in diameter (stenosis) of the proximal right renal artery entrapped by the right diaphragmatic crus. This pathology, unlike common renal artery stenosis, sometimes requires surgical decompression or an aortorenal bypass graft, because renal angioplasty with stenting is reported to be at risk of complication by a fracture of the stent. However, the patient rejected surgical decompression for fear of deterioration of his athletic ability. Therefore we decided to follow up his blood pressure and renal size by ultrasound every six months. Renovascular hypertension caused by diaphragmatic entrapment is a very rare disease. The diagnosis may be overlooked easily at angiography if optimal views are not obtained. It is important to display images of the renal arteries, the celiac artery and the superior mesenteric artery in both inspiration and expiration.

  6. [Arterial hypertension in children].

    PubMed

    Mota-Hernández, F

    1993-07-01

    It is considered hypertension in children, the persistent increase of the blood pressure values above percentile 95 for age and sex, in no less than three determinations, with adequate register techniques. Blood pressure is maintained mainly by the regulation of metabolism of sodium and water in the intravascular space, through the adequate balance of intake, filtration, reabsorption and renal throughout. It is also regulated by hormonal factors. Weight gain control in teen-agers could be useful to prevent high blood pressure in adults. In children, it is generally secondary to renal, reno-vascular, endocrinological or tumoral diseases. Clinical manifestations and the recommended diagnostic procedures are analysed to detect the most frequent causes of hypertension at different ages. Most cases response with antihypertensive drugs in combination with hyposodic diet. For the hypertensive crisis, asa diuretics and powerful antihypertensive drugs may be employed. Patients with chronic renal insufficiency could also need dialytic treatments. Renovascular diseases require almost always invasive treatments. Better prognosis in children with severe high blood pressure is related with recent diagnostic procedures, surgical techniques and antihypertensive drugs improvements.

  7. [Arterial hypertension and prediabetes].

    PubMed

    Boned Ombuena, Patricia; Rodilla Sala, Enrique; Costa Muñoz, José Antonio; Pascual Izuel, José María

    2016-11-04

    The aim of this study was to assess the factors related to new diabetes in hypertensive. This prospective follow-up study involved 2588 non-diabetic, hypertensive patients. The total follow-up was 15053 patient-years with a median of 3.4 years (interquartile interval 1.4-6.8). During the follow-up 333 (13%) patients had new diabetes, with a conversion rate of 2.21 (95% confidence interval [CI], 1.98-2.46) 100/patients/year. In a Cox proportional hazard model including baseline characteristics and modifications during the follow up the three components of metabolic syndrome (excluding blood pressure and glucose values) HR 1.69 (95% CI, 1.36-2.09), family history of diabetes HR 1,49 (95% CI, 1,20-1,85) and baseline blood glucose ≥110 mg/dl HR 7.84 (95% CI, 5.99-10.29) were the most important factors related to new diabetes. Weight variation during the follow up, and statins, beta-bloquers or diuretic treatment did not increase the risk of new diabetes, blood pressure control at the end of study reduce the risk HR 0,74 (95% CI, 0.61-0.91). In hypertensive non-diabetic patients in primary prevention the factors related to new diabetes can easily identified at the beginning of follow up. Being obese, with family history of diabetes, and glucose values ≥110 mg/dl dramatically increase the risk of developing new diabetes. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  8. Epoprostenol Therapy for Pulmonary Arterial Hypertension.

    PubMed

    Akagi, Satoshi; Nakamura, Kazufumi; Matsubara, Hiromi; Ogawa, Aiko; Sarashina, Toshihiro; Ejiri, Kentaro; Ito, Hiroshi

    2015-01-01

    Pulmonary arterial hypertension (PAH) is characterized by elevation of pulmonary artery pressure caused by pulmonary vasoconstriction and vascular remodeling, which leads to right heart failure and death. Epoprostenol (prostaglandin I2) has a potent short-acting vasodilator property, and intravenous continuous epoprostenol is therefore used for treatment of PAH. Here we review evidence for the usefulness of intravenous continuous epoprostenol therapy in patients with PAH. Epoprostenol therapy is effective in idiopathic PAH patients and in patients with PAH associated with connective tissue disease, portal hypertension or congenital heart diseases, but it is not effective in patients with pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis. High-dose epoprostenol therapy markedly improved hemodynamics in some patients with PAH, possibly due to reverse remodeling of pulmonary arteries. This therapy has several side effects and complications such as headache, hypotension and catheter-related infections. Intravenous continuous epoprostenol is an effective treatment, but there are still some problems to be resolved.

  9. [Chronotherapy in arterial hypertension].

    PubMed

    Bendersky, M

    2015-01-01

    The blood pressure profile in most normo- and hypertensive subjects are currently known, as well as the impact their changes induced on the cardio- and cerebrovascular risk. Ambulatory blood pressure monitoring (ABPM) has contributed greatly to the knowledge of this parameter. It to correct the schedule of drug administration (chronotherapy) with changes in any component of the BP profile that have better correlation with risk. These include the nocturnal decrease and the morning BP surge. Investigations in this direction are still scarce, and multicenter studies need to be conducted that can answer the true preventive impact of such modifications.

  10. New therapies for arterial hypertension.

    PubMed

    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.

  11. [Pulmonary arterial hypertension and BMP system abnormality].

    PubMed

    Otsuka, Fumio

    2008-11-01

    Genetic analysis has uncovered that familial and idiopathic pulmonary arterial hypertension (PAH) is linked to germline mutations in BMP type II receptor (BMPRII). PAH is characterized by enhanced remodeling of pulmonary arteries due to arterial smooth muscle cell proliferation. BMPRII mutations contribute to abnormal mitotic responses to BMP ligands in pulmonary artery smooth muscle cells. Unbalanced Smad signaling induced by BMP and TGFbeta is functionally involved in the pathogenesis of PAH. BMPRII mutations also increase the susceptibility of endothelial cell apoptosis. The combination of increased endothelial injury and impaired suppression of smooth muscle cell proliferation is critical for the cellular pathogenesis of PAH. However, the detailed molecular mechanism leading to severe vascular remodeling caused by BMPRII mutations has yet to be elucidated.

  12. [Management of severe arterial hypertension].

    PubMed

    Leeman, M

    2015-09-01

    Severe arterial hypertension is defined as a systolic blood pressure (BP) ≥180 mmHg and/or a diastolic BP ≥ 110 mmHg. Initial assessment is to identify acute, ongoing, target-organ damage such as pulmonary edema, aortic dissection, ... (hypertensive emergency). If so, the patient requires urgent and specific management in a hospital setting. More commonly, however, BP in the severe range is relatively asymptomatic and not associated with end-organ damage (hypertensive urgency). Management can usually be carried out in the ambulatory setting. Severe hypertension should first be confirmed after a period of rest in a quiet room. If BP remains in the severe range, an antihypertensive drug can be initiated. Otherwise, the patient should be referred for further evaluation within a few days ; however, an antihypertensive treatment could be started immediately if there is concern that urgent outpatient follow-up cannot be ensured or if the patient is at high cardiovascular risk. The choice of the first drug should be tailored according to associated conditions and possible contraindications. Some guidelines recommend starting therapy with an antihypertensive combination of two drugs. In all cases, rapid and excessive reduction in BP, which could compromise organ perfusion, must be avoided, especially in elderly patients. In the short-term (days), BP should be progressively lowered to < 160/100 mmHg. In the long term, a BP < 140/90 mmHg should be obtained.

  13. Circulating levels of cytokines and their endogenous modulators in patients with mild to severe congestive heart failure due to coronary artery disease or hypertension.

    PubMed

    Testa, M; Yeh, M; Lee, P; Fanelli, R; Loperfido, F; Berman, J W; LeJemtel, T H

    1996-10-01

    This study sought to determine the circulating levels of cytokines and their respective endogenous modulators in patients with congestive heart failure of variable severity. Activation of immune elements localized in the heart or periphery, or both, may promote release of cytokines in patients with congestive heart failure. Although an increased circulating level of tumor necrosis factor-alpha (TNF-alpha) and its soluble receptor type II (sTNF-RII) is well documented, less is known about other cytokines (i.e., interleukin-1-beta [IL-1-beta], interleukin-6 [IL-6] and interleukin-2 [IL-2] and their soluble receptor/receptor antagonists). Circulating levels of TNF-alpha and sTNF-RII, IL-1-beta, IL-1 receptor antagonist (IL-1-Ra), IL-6, IL-6 soluble receptor (IL-6-sR), IL-2 and IL-2 soluble receptor-alpha were measured using enzyme-linked immunosorbent assay kits (Quantikine, R&D Systems) in 80 patients with congestive heart failure due to coronary artery disease or hypertension. The severity of their symptoms, which ranged from New York Heart Association functional class I to IV, was confirmed by measurement of peak oxygen consumption. The percentage of patients with elevated levels of cytokines and their corresponding soluble receptor/receptor antagonists significantly increased with functional class. For TNF-alpha and IL-1-beta, the percentage of patients with elevated levels of soluble receptor/receptor antagonists was higher than that of patients with elevated levels of the cytokine itself. For IL-6, the percentage of patients with elevated levels of IL-6-sR tended to be lower than that of patients with elevated levels of IL-6. All but two patients had undetectable levels of IL-2, and all but seven had levels of IL-2-sR within a normal range. In patients with congestive heart failure, circulating levels of cytokines increased with the severity of symptoms. In these patients, circulating levels of sTNF-RII and IL-1-Ra are more sensitive markers of immune activation

  14. Genetics of pulmonary arterial hypertension.

    PubMed

    Elliott, C Gregory

    2013-12-01

    Painstaking research led to the discovery of gene mutations responsible for heritable forms of pulmonary arterial hypertension (PAH). Mutations in the gene BMPR2, which codes for a cell surface receptor (BMPRII), cause the approximately 80% of heritable cases of PAH. Less commonly mutations in ALK1, CAV1, ENG, and SMAD9, and newly discovered mutations in KCNK3, may cause heritable PAH. Other family members of many patients diagnosed with idiopathic PAH may be diagnosed with PAH. Genetic counseling and testing should be offered to patients diagnosed with heritable or idiopathic PAH.

  15. Evaluation and management of the patient with pulmonary arterial hypertension.

    PubMed

    Rubin, Lewis J; Badesch, David B

    2005-08-16

    Increased pressure in the pulmonary circulation, or pulmonary hypertension, is a common disorder that may complicate various cardiopulmonary conditions, including severe obstructive airways disease and left ventricular dysfunction. An increase in pulmonary arterial pressure that is not due to coexistent cardiopulmonary disease, known as pulmonary arterial hypertension, may occur in the absence of a demonstrable cause (idiopathic or familial); as a complication of systemic conditions, such as connective tissue disease, HIV infection, or chronic liver disease; or as a result of the use of fenfluramine anorexigens, amphetamines, or cocaine. The development of disease-specific therapies for pulmonary arterial hypertension over the past decade underscores the importance of diagnosing pulmonary hypertension early in the course of the condition and implementing a treatment strategy that is based on the condition's cause and severity. In this review, the authors present approaches to the diagnosis and management of pulmonary arterial hypertension, using a hypothetical case to highlight the key management points.

  16. Hypertensive encephalopathy complicating transplant renal artery stenosis.

    PubMed Central

    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. Images Fig. 1 PMID:6377286

  17. [Treatment of pulmonary arterial hypertension].

    PubMed

    Roman, Antonio; López-Meseguer, Manuel; Domingo, Enric

    2015-06-22

    Treatment of pulmonary arterial hypertension has achieved significant progress over the past 20 years. Currently, 3 groups of drugs have proven useful for the treatment of this disease: endothelin receptor antagonist, phosphodiesterase inhibitors and prostacyclin and its analogues. It is recommended to initiate treatment with one of these drugs, the choice depending on the initial severity of patient disease and the preferences of the treating physician. When the patient does not have a satisfactory response, new drugs acting at a different pathway are most commonly added. At this time, considering referral for lung transplantation could be an alternative. Most experts recommend grouping maximum experience in what is known as expert centers. Treatment has led to better survival in these patients, but there is still a long way to cure this life-threatening disease.

  18. [Aerosolized iloprost therapy for pulmonary hypertensive crisis in 4 patients with idiopathic pulmonary arterial hypertension].

    PubMed

    Deng, Ke-wu; Zhou, Yu-jie; Xu, Xi-qi; Wu, Ming-ying; Wang, Guo-hong; Bian, Hong; Chen, Bo; Wang, Chun-bo

    2012-10-01

    To summary the efficacy and safety of aerosolized iloprost in patients with pulmonary hypertensive crisis. On the basis of conventional therapy, aerosolized iloprost (10 µg per time for 10 - 15 min in 2 hours interval, 8 times per day) was administered to four patients with idiopathic pulmonary arterial hypertension and pulmonary hypertensive crisis. Blood pressure, heart rate, systemic artery oxygen saturation, systolic pulmonary arterial pressure (sPAP) measured by echocardiography and the adverse events were analyzed. After aerosolized iloprost therapy, sPAP was significantly decreased and systemic artery oxygen saturation was improved. Adverse events (nausea, vomiting, diarrhea, dry cough) were observed in two patients, and the iloprost use was stopped in one patient due to severe vomiting and diarrhea. Aerosolized iloprost could significantly reduce the sPAP and improve the systemic artery oxygen saturation in patients with pulmonary hypertension crisis.

  19. Diastolic dysfunction in arterial hypertension.

    PubMed

    de Simone, G; Palmieri, V

    2001-01-01

    Left ventricular diastolic properties are important markers of pump function and are frequently abnormal when myocardial insults alter tissue structure. Alterations can be limited to the early diastolic phase (early active relaxation) or to late diastolic filling (late ventricular compliance), but more often involve regulation of both phases of diastole. In asymptomatic patients with arterial hypertension, left ventricular relaxation is often prolonged, independently, at least in part, of cardiac loading conditions and left ventricular geometry, but this abnormality is associated with early signs of systolic dysfunction. Uncontrolled hypertension, diabetes, and obesity are most often associated with ischemic heart disease and impaired diastolic function. Reducing blood pressure with antihypertension therapy will reduce myocardial afterload, regress LVH, and improve systolic and diastolic function. In patients with symptoms of CHF with a normal ejection fraction, however, changes in therapy may be indicated. Greater emphasis should be placed on using medications that decrease myocardial load, but also reduce the effects of neurohormonal activation. (c)2001 by Le Jacq Communications, Inc.

  20. Small artery remodeling in hypertension and diabetes.

    PubMed

    Rizzoni, Damiano; Agabiti Rosei, Enrico

    2006-04-01

    The development of structural changes in the systemic vasculature is the end result of established hypertension. In essential hypertension, small artery smooth muscle cells are restructured around a smaller lumen, and there is no net growth of the vascular wall, whereas in some secondary forms of hypertension and in non-insulin-dependent diabetes mellitus, a hypertrophic remodeling may be detected. Indices of small resistance artery structure, such as the tunica media to internal lumen ratio, may have a strong prognostic significance in hypertensive patients. Various antihypertensive drugs seem to have different effects on vascular structure. A complete normalization of small resistance artery structure was demonstrated in hypertensive patients, after prolonged and effective therapy with angiotensin-converting enzyme inhibitors, angiotensin II-receptor blockers, and calcium antagonists. Few data are available in diabetic hypertensive patients; however, blockade of the renin-angiotensin system seems to be effective in this regard.

  1. [Arterial hypertension and metabolic disorders].

    PubMed

    Dzherieva, I S; Volkova, N I

    2010-01-01

    Combination of arterial hypertension (AH) and metabolic disorders accelerates development of organic lesions in target organs. As shown in recent prospective studies, myocardial hypertrophy rate closely correlated with severity of metabolic disturbance. The thickness of interventricular septum and posterior wall show stronger dependence of severity of metabolic disorders than left ventricular density while left atrial enlargement is correlates with fasting glycemia and excess body mass. There is close relationship between microalbuminurea and hyperinsulinemia and the number of metabolic syndrome components is linearly correlated with glomerular filtration rate below 60 ml/min. It is shown that rigidity of arteries is a new independent risk factor of cardiovascular complications in obese patients. Moreover, metabolic disturbances cause affective disorders that impair quality of life and therapy motivation. Combination of AH, metabolic disturbances, and borderline psychic disorders dictated consideration of abnormal melatonin secretion as a condition developing as a consequence of disturbed adaptive circadian rhythms. This hypothesis was prompted by the discovery of the so-called "clock genes" in the central nervous system and practically all peripheral organs including heart, vessels, and adipose tissue.

  2. Iranian Pulmonary Arterial Hypertension Registry.

    PubMed

    Masjedi, Mohammad Reza; Fahimi, Fanak; Sharif-Kashani, Babak; Malek Mohammad, Majid; Saliminejad, Leila; Monjazebi, Fateme

    2015-01-01

    Idiopathic pulmonary arterial hypertension (IPAH) is a fatal disorder with a prevalence of 8.6 per million. We introduce a registry website for IPAH and PAH patients ( www.IPAH.ir) for access and efficient delivery of government-aided and subsidized antihypertensive medications. The IPAH registry was opened in November 2009. Information of IPAH and PAH patients with a username and password were uploaded in the site. Data entry was possible only via the physicians and healthcare organizations via internet that were given a personalized username and password for entry. Following the patients' profile submission, a scientific committee composed of a cardiologist and a pulmonologist who were selected by the Ministry of Health of Iran (MOH), evaluated the data. The eligibility of the patient to receive the medications was confirmed after evaluation. If the patient was eligible, 82% of the Bosentan cost was paid by MOH. To date, one hundred and sixteen patients (82 females, 34 males) have been registered. The mean pulmonary artery pressure by right heart catheterization was 69.24±17 mmHg (ranging from 35 to 110 mmHg). The first online Iranian registry program for IPAH and PAH patients is believed to supply essential information for health care providers in the field.

  3. Pulmonary arterial hypertension: Basic knowledge for clinicians.

    PubMed

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

    2016-10-01

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

  4. Genetics Home Reference: pulmonary arterial hypertension

    MedlinePlus

    ... 4 Sources for This Page Austin ED, Loyd JE. The genetics of pulmonary arterial hypertension. Circ Res. ... Gräf S, Hinderhofer K, Humbert M, Keiles SB, Loyd JE, Morrell NW, Newman JH, Soubrier F, Trembath RC, ...

  5. Tinnitus and arterial hypertension: a systematic review.

    PubMed

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

    2015-11-01

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

  6. Pulmonary arterial hypertension in congenital heart diseases.

    PubMed

    Beghetti, Maurice; Tissot, Cecile

    2009-08-01

    Pulmonary hypertension complicates the course of many children and adults with congenital heart diseases (CHDs). The increase in pulmonary pressure associated with CHD is secondary to either increased pulmonary blood flow or increased postcapillary pressures. Pulmonary arterial hypertension is in the vast majority associated with congenital cardiac shunts. Despite major advances in the understanding of the regulation of the pulmonary vascular bed and the pulmonary endothelial lesions leading to pulmonary vascular disease, despite the advances in surgical repair and the discovery of potential therapies in the pre- and postoperative period, pulmonary hypertension still carries a significant mortality and morbidity in patients with CHD. The recent introduction of targeted therapies in other forms of pulmonary arterial hypertension has led to a renewed interest in pulmonary hypertension associated with CHD and this particularly for the most advanced form, the so-called Eisenmenger syndrome (ES). This review summarizes the current knowledge on pulmonary hypertension associated with CHD, focusing on the pathophysiology and treatment of ES.

  7. [Pulmonary hypertension due to left heart diseases].

    PubMed

    Vachiéry, Jean-Luc; Adir, Yochai; Barberà, Joan Albert; Champion, Hunter; Coghlan, John Gerard; Cottin, Vincent; De Marco, Teresa; Galiè, Nazzareno; Ghio, Stefano; Gibbs, J Simon R; Martinez, Fernando; Semigran, Marc; Simonneau, Gerald; Wells, Athol; Seeger, Werner

    2014-10-01

    Pulmonary hypertension (PH), a common complication of left heart diseases (LHD), negatively impacts symptoms, exercise capacity, and outcome. Although the true prevalence of PH-LHD is unknown, a subset of patients might present significant PH that cannot be explained by a passive increase in left-sided filling pressures. The term "out-of-proportion" PH has been used to identify that population without a clear definition, which has been found less than ideal and created confusion. We propose a change in terminology and a new definition of PH due to LHD. We suggest to abandon "out-of-proportion" PH and to distinguish "isolated post-capillary PH" from "post-capillary PH with a pre-capillary component" on the basis of the pressure difference between diastolic pulmonary artery pressure and pulmonary artery wedge pressure. Although there is no validated treatment for PH-LHD, we provide insights into management and discuss completed and randomized trials in this condition. Finally, we provide recommendations for future clinical trials to establish safety and efficacy of novel compounds to target this area of unmet medical need. (J Am Coll Cardiol 2013;62:D100-8) ©2013 by the American College of Cardiology Foundation.

  8. Pulmonary hypertension due to left heart diseases.

    PubMed

    Vachiéry, Jean-Luc; Adir, Yochai; Barberà, Joan Albert; Champion, Hunter; Coghlan, John Gerard; Cottin, Vincent; De Marco, Teresa; Galiè, Nazzareno; Ghio, Stefano; Gibbs, J Simon R; Martinez, Fernando; Semigran, Marc; Simonneau, Gerald; Wells, Athol; Seeger, Werner

    2013-12-24

    Pulmonary hypertension (PH), a common complication of left heart diseases (LHD), negatively impacts symptoms, exercise capacity, and outcome. Although the true prevalence of PH-LHD is unknown, a subset of patients might present significant PH that cannot be explained by a passive increase in left-sided filling pressures. The term "out-of-proportion" PH has been used to identify that population without a clear definition, which has been found less than ideal and created confusion. We propose a change in terminology and a new definition of PH due to LHD. We suggest to abandon "out-of-proportion" PH and to distinguish "isolated post-capillary PH" from "post-capillary PH with a pre-capillary component" on the basis of the pressure difference between diastolic pulmonary artery pressure and pulmonary artery wedge pressure. Although there is no validated treatment for PH-LHD, we provide insights into management and discuss completed and randomized trials in this condition. Finally, we provide recommendations for future clinical trials to establish safety and efficacy of novel compounds to target this area of unmet medical need.

  9. Novel serum biomarkers in pulmonary arterial hypertension.

    PubMed

    McGlinchey, Neil; Johnson, Martin K

    2014-01-01

    Pulmonary arterial hypertension (PAH) remains a difficult-to-treat condition with high mortality. Biomarkers are utilized to aid with diagnosis, prognostication and response to treatment. A clinically useful and PAH-specific single biomarker that is easy to measure remains elusive. This is in part due to the heterogeneity of PAH and its complex etiology. Brain natriuretic peptide and its N-terminal fragment are currently the most widely used serum markers; however, several novel serum biomarkers have been investigated recently. Taken individually, the evidence for each of these seems provisionally promising though currently weak overall. It is likely that a multibiomarker panel will be recommended in the future, with the optimal combination yet to be determined.

  10. Medical treatment update on pulmonary arterial hypertension.

    PubMed

    Enderby, Cher Y; Burger, Charles

    2015-09-01

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

  11. Diagnosis and assessment of pulmonary arterial hypertension.

    PubMed

    Badesch, David B; Champion, Hunter C; Sanchez, Miguel Angel Gomez; Hoeper, Marius M; Loyd, James E; Manes, Alessandra; McGoon, Michael; Naeije, Robert; Olschewski, Horst; Oudiz, Ronald J; Torbicki, Adam

    2009-06-30

    The diagnosis and assessment of pulmonary arterial hypertension is a rapidly evolving area, with changes occurring in the definition of the disease, screening and diagnostic techniques, and staging and follow-up assessment. The definition of pulmonary hypertension has been simplified, and is now based on currently available evidence. There has been substantial progress in advancing the imaging techniques and biomarkers used to screen patients for the disease and to follow up their response to therapy. The importance of accurate assessment of right ventricular function in following up the clinical course and response to therapy is more fully appreciated. As new therapies are developed for pulmonary arterial hypertension, screening, prompt diagnosis, and accurate assessment of disease severity become increasingly important. A clear definition of pulmonary hypertension and the development of a rational approach to diagnostic assessment and follow-up using both conventional and new tools will be essential to deriving maximal benefit from our expanding therapeutic armamentarium.

  12. Pulmonary arterial hypertension in primary amyloidosis

    PubMed Central

    Emerson, Lyska L.; Bull, David A.; Hatton, Nathan; Nativi-Nicolai, Jose; Hildebrandt, Gerhard C.; Ryan, John J.

    2016-01-01

    Abstract Amyloidosis involves extravascular deposition of fibrillar proteins within tissues and organs. Primary light chain amyloidosis represents the most common form of systemic amyloidosis involving deposition of monoclonal immunoglobulin light chains. Although pulmonary amyloid deposition is common in primary amyloidosis, clinically significant pulmonary amyloidosis is uncommon, and elevated pulmonary artery pressures are rarely observed in the absence of other underlying etiologies for pulmonary hypertension, such as elevated filling pressures secondary to cardiac amyloid. In this case report, we present a patient with primary light chain amyloidosis and pulmonary arterial hypertension in the setting of pulmonary vascular and right ventricular myocardial amyloid deposition. PMID:27252852

  13. Hemorheological abnormalities in human arterial hypertension

    NASA Astrophysics Data System (ADS)

    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.

  14. The right ventricle in pulmonary arterial hypertension.

    PubMed

    Naeije, Robert; Manes, Alessandra

    2014-12-01

    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. ©ERS 2014.

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

    PubMed

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

    2016-09-01

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

  16. [Left ventricular function in pulmonary arterial hypertension].

    PubMed

    Khomaziuk, V A

    1998-12-01

    Echocardiographic evaluation was done of left ventricular functional state in 90 patients with primary and secondary pulmonary arterial hypertension with and without intercavitary shunting. Changes in left ventricular function were identified in 86% cases; they reflected disturbances in both ventricles compensatory interaction. The degree of changes depended on the degree of dilatation of the right ventricle and level of interchamber shunting.

  17. MicroRNAs in Pulmonary Arterial Hypertension

    PubMed Central

    Zhou, Guofei; Chen, Tianji

    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 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

  18. hypertensive intracranial bleed due to mid aortic syndrome.

    PubMed

    Poovazhagi, Varadarajan; Pauline, Leema; Balakrishnan, N

    2014-03-01

    The authors describe an 11-y-old child with intracranial bleed due to malignant hypertension. Child presented with hypertension, right hemiparesis, feeble femoral pulses and lower limb blood pressure less than the upper limb. CT angiogram revealed narrowing of the abdominal aorta with thinned out left renal artery and hypoplasia of the left kidney. A diagnosis of Mid aortic syndrome was arrived at. CT brain revealed left ganglio capsular bleed. Child was treated with antihypertensives and steriods in view of suspected Takayasu arteritis. Child recovered with minimal hemiparesis and is being followed up.

  19. [Treatment of arterial hypertension in children].

    PubMed

    Bensman, A

    1988-01-01

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

  20. Pulmonary Arterial Hypertension: The Clinical Syndrome

    PubMed Central

    Lai, Yen-Chun; Potoka, Karin C.; Champion, Hunter C.; Mora, Ana L.; Gladwin, Mark T.

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disorder in which endothelial dysfunction and vascular remodeling obstruct small pulmonary arteries, resulting in increased pulmonary vascular resistance and pulmonary pressures. This leads to reduced cardiac output, right heart failure, and ultimately death. In this review, we attempt to answer some important questions commonly asked by patients diagnosed with PAH pertaining to the disease, and aim to provide an explanation in terms of classification, diagnosis, pathophysiology, genetic etiologies, demographics, and prognostic factors. Furthermore, important molecular pathways that are central to the pathogenesis of PAH are reviewed, including nitric oxide, prostacyclin, endothelin-1, reactive oxygen species, and endothelial and smooth muscle proliferation. PMID:24951762

  1. Immunity in arterial hypertension: associations or causalities?

    PubMed Central

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

    2015-01-01

    Numerous studies describe associations between markers of inflammation and arterial hypertension (aHT), but does that imply causality? Interventional studies that reduce blood pressure reduced also markers of inflammation, but does immunosuppression improve hypertension? Here, we review the available mechanistic data. Aberrant immunity can trigger endothelial dysfunction but is hardly ever the primary cause of aHT. Innate and adaptive immunity get involved once hypertension has caused vascular wall injury as immunity is a modifier of endothelial dysfunction and vascular wall remodelling. As vascular remodelling progresses, immunity-related mechanisms can become significant cofactors for cardiovascular (CV) disease progression; vice versa, suppressing immunity can improve hypertension and CV outcomes. Innate and adaptive immunity both contribute to vascular wall remodelling. Innate immunity is driven by danger signals that activate Toll-like receptors and other pattern-recognition receptors. Adaptive immunity is based on loss of tolerance against vascular autoantigens and includes autoreactive T-cell immunity as well as non-HLA angiotensin II type 1 receptor-activating autoantibodies. Such processes involve numerous other modulators such as regulatory T cells. Together, immunity is not causal for hypertension but rather an important secondary pathomechanism and a potential therapeutic target in hypertension. PMID:25762356

  2. [Pathogenesis and epidemiology of arterial hypertension].

    PubMed

    Pardell, H; Armario, P; Hernández, R

    1998-01-01

    The pathogenesis of arterial hypertension is more clearly understood today because of the availability of data enabling identification of a certain number of precipitating factors. From a genetic standpoint, hypertension would appear to be a multifactorial polygenic disorder with a tendency to interact with certain environmental factors. The latter are mainly related to lifestyle and are potentially modifiable. Obesity during childhood and adolescence is the main predictive factor for hypertension. It has been suggested that the underlying mechanism could well be hyperinsulinaemia, which induces hyperactivity of the sympathetic nervous system. The mechanisms of the relationship between hypertension and alcohol are still unclear. However, in many countries, excessive alcohol consumption has been reported to be a significant factor in the development of arterial hypertension. The negative effect of a sedentary lifestyle on blood pressure has been widely demonstrated. In addition, it has also been shown that regular physical exercise under aerobic conditions leads to a reduction in blood pressure levels. An excessive sodium intake is also responsible for inducing arterial hypertension through increases in cardiac output and effects on vascular reactivity and contractility. Similarly, restricting sodium intake leads to a reduction in blood pressure levels. Smoking--namely, certain components of tobacco smoke--would appear to have both short and long term effects on blood pressure. These contributing factors all have specific effects on cardiac output and peripheral resistance in individuals. At the community level, the impact of hypertension is particularly significant. Prevalence is strongly influenced by the type of population studied, although it is generally estimated that this disease affects between 10 and 20% of the adult population and is responsible for 5.8% of all deaths worldwide. The direct and indirect costs of the disease are particularly high and are

  3. A review of pulmonary arterial hypertension

    PubMed Central

    Gan, C.T.; Noordegraaf, A. Vonk; Marques, K.M.J.; Bronzwaer, J.G.F.; Postmus, P.E.; Boonstra, A.

    2004-01-01

    Medical therapy for pulmonary arterial hypertension (PAH) focuses on pulmonary vascular remodelling and smooth muscle cell proliferation. This article covers the drugs which are approved or are in sight and the evidence-based treatment strategies that target the different pathobiological pathways, emanated from the World Health Organisation Symposium on Pulmonary Hypertension in Venice, June 2003. In addition we briefly look at the 'Venice consensus' on surgical treatment. In the past five and a half years more than 360 patients were seen for pulmonary hypertension in the Free University Medical Centre (VUmc). Present-day treatment, research studies and novel treatment strategies in the VUmc will be reviewed. Future treatments will be on the basis of insights into pathobiology, pathogenesis and genes in PAH and should focus on drug combinations, which theoretically target different or similar pathobiological pathways. PMID:25696358

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

    PubMed

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

    2014-01-01

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

  5. [Pregnancy in pulmonary arterial hypertension patients].

    PubMed

    Rosengarten, Dror; Kramer, Mordechai R

    2013-09-01

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

  6. Takotsubo cardiomyopathy after treatment of pulmonary arterial hypertension

    PubMed Central

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

    2012-01-01

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

  7. Hypertension and stable coronary artery disease: an overview.

    PubMed

    Pedrinelli, Roberto; Ballo, Piercarlo; Fiorentini, Cesare; Galderisi, Maurizio; Ganau, Antonello; Germanò, Giuseppe; Innelli, Pasquale; Paini, Anna; Perlini, Stefano; Salvetti, Massimo; Zacà, Valerio

    2013-08-01

    Systemic hypertension is highly prevalent in stable coronary artery disease, a pervasive comorbidity complicating the diagnostic performance and interpretation of non-invasive provocative tests in chest pain patients because of the ischaemic signals generated, despite normal or near normal coronary arteries, by hearts structurally readapted by long-term exposure to raised systemic blood pressure. Additional and unresolved problems posed by arterial hypertension in patients with stable coronary artery disease regard the benefits of antihypertensive treatment due to reports of irrelevant, if not detrimental, effect of blood pressure (BP) lowering in averting coronary relapses as well as the lack of association between BP levels and incident coronary events in survivors from acute myocardial infarction. Uncertainties extend to BP-independent cardioprotective effects of antihypertensive drugs, although the efficacy of renin-angiotensin system blockers in the long-term prevention of cardiovascular events in stable coronary artery disease patients has been shown by several studies, particularly when combined with amlodipine, a dihydropiridine calcium channel blocker. In contrast, the long-term effect of beta-blockers, the antihypertensive class most used in that clinical category, is not supported by strong evidence except that generated in patients with systolic dysfunction and early postmyocardial infarction recovery periods.

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

    PubMed

    Szczepaniak-Chicheł, Ludwina; Tykarski, Andrzej

    2012-10-01

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

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

    PubMed

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

    2011-04-01

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

  10. Advances in pediatric pulmonary arterial hypertension.

    PubMed

    Ivy, Dunbar

    2012-03-01

    Pulmonary arterial hypertension (PAH) is an important cause of morbidity and mortality in children. Approved medications for the treatment of adult PAH have been used to treat children, but evidence-based treatment algorithms for children are lacking. Pediatric PAH registries have begun to define the incidence and prevalence of idiopathic PAH and PAH associated with congenital heart disease. A pediatric-specific classification of pulmonary hypertensive vascular disease has been proposed. Furthermore, the first randomized placebo-controlled trial of type-5 phosphodiesterase therapy in treatment-naïve children with PAH has been completed and reported. This trial highlights the importance of the difficulties of performing clinical trials in children with targeted PAH therapy as well as the importance of long-term follow-up of adverse events. Classification, clinical trials, and therapy for children with PAH must take into account the unique aspects of PAH in children.

  11. Developing treatments for pulmonary arterial hypertension

    PubMed Central

    Wilkins, Martin R.

    2013-01-01

    Developing new treatments for pulmonary arterial hypertension (PAH) is a challenge. We have enjoyed success with regulatory approvals for three drug classes—prostanoids, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors. But we have also seen some disappointing results, for example, from studies with vasoactive intestinal polypeptide, statins and tergolide. Animal models are an unreliable predictor of efficacy in humans. The best model for the disease is the patient. This review discusses three major issues facing the evaluation of drugs in PAH patients—target validation, choosing the right dose, and early trial design. PMID:23662193

  12. [Anticoagulation therapy in pulmonary arterial hypertension].

    PubMed

    Akagi, Satoshi; Kusano, Kengo Fukushima

    2008-11-01

    Vascular thrombosis implicates in the pathogenesis of pulmonary arterial hypertension (PAH). Anticoagulation therapy (warfarin) has been recommended by many experts in the treatment of PAH. However, the long-term effectiveness of anticoagulation therapy remains controversial. Because of the various drugs, such as epoprostenol, bosentan, and sildenafil, for the treatment of PAH recently, warfarin alone is not a realistic therapy for PAH. Accordingly we reviewed the previous manuscript regarding anticoagulation therapy for PAH, and looked at the current role of anticoagulation therapy in Japan.

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

    PubMed

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

    2013-10-15

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

  14. The metabolic basis of pulmonary arterial hypertension.

    PubMed

    Sutendra, Gopinath; Michelakis, Evangelos D

    2014-04-01

    Pulmonary arterial hypertension (PAH) is a vascular remodeling disease of the lungs resulting in heart failure and premature death. Although, until recently, it was thought that PAH pathology is restricted to pulmonary arteries, several extrapulmonary organs are also affected. The realization that these tissues share a common metabolic abnormality (i.e., suppression of mitochondrial glucose oxidation and increased glycolysis) is important for our understanding of PAH, if not a paradigm shift. Here, we discuss an emerging metabolic theory, which proposes that PAH should be viewed as a syndrome involving many organs sharing a mitochondrial abnormality and explains many PAH features and provides novel biomarkers and therapeutic targets. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Potassium channels in pulmonary arterial hypertension.

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2010-01-01

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

  17. Tadalafil as treatment for idiopathic pulmonary arterial hypertension.

    PubMed

    de Carvalho, Adriana Castro; Hovnanian, André Luiz; Fernandes, Caio Julio César dos Santos; Lapa, Mônica; Jardim, Carlos; Souza, Rogério

    2006-11-01

    Phosphodiesterase inhibitors like sildenafil have already been shown to improve functional capacity and hemodynamics in the treatment of pulmonary arterial hypertension. Few studies address the effects of new phosphodiesterase inhibitors as tadalafil. We report a case of a patient with idiopathic pulmonary arterial hypertension in functional class IV (New York Heart Association) with significant response to treatment with tadalafil.

  18. Inhaled treprostinil and pulmonary arterial hypertension

    PubMed Central

    Nadler, Samuel T; Edelman, Jeffrey D

    2010-01-01

    Multiple conditions result in development of pulmonary hypertension. Pulmonary arterial hypertension (PAH) is the subclassification of pulmonary hypertension, in which known or unknown underlying conditions lead to similar intrinsic alterations in the pulmonary vasculature. PAH is a progressive condition characterized by restricted blood flow through the pulmonary circulation leading to poor survival in the absence of effective therapy. Over the last two decades, new therapeutic agents have substantially improved the course and prognosis for PAH patients. Three available classes of drugs, ie, prostacyclins, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors provide multiple options for treatment of PAH. Endothelin receptor antagonists and phosphodiesterase-5 inhibitors are administered orally, whereas prostacyclin therapies are delivered by continuous intravenous or subcutaneous infusion, or as aerosols by nebulization. Because of the risks and inconveniences associated with administration, prostacyclins are typically reserved for patients with more advanced disease or progression despite oral therapy. Inhaled administration may be a safer and easier route for prostacyclin administration. Treprostinil is a prostacyclin analog that has been demonstrated to be effective when administered by continuous subcutaneous or intravenous infusion, and more recently by nebulization. PMID:21191432

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

    PubMed

    Laurent, Stéphane; Boutouyrie, Pierre

    2015-03-13

    Pathophysiological studies have extensively investigated the structural factor in hypertension, including large and small artery remodeling and functional changes. Here, we review the recent literature on the alterations in small and large arteries in hypertension. We discuss the possible mechanisms underlying these abnormalities and we explain how they accompany and often precede hypertension. Finally, we propose an integrated pathophysiological approach to better understand how the cross-talk between large and small artery changes interacts in pressure wave transmission, exaggerates cardiac, brain and kidney damage, and lead to cardiovascular and renal complications. We focus on patients with essential hypertension because this is the most prevalent form of hypertension, and describe other forms of hypertension only for contrasting their characteristics with those of uncomplicated essential hypertension. © 2015 American Heart Association, Inc.

  20. [Nephropathy associated with arterial hypertension: genes and Barker's hypothesis].

    PubMed

    Zoccali, C

    2002-01-01

    For about three decades glomerular diseases have been the most intensively investigated research area in nephrology. The increasing proportion of patients with end-stage renal disease (ESRD) secondary to hypertension has now revived interest in hypertension. Prospective studies have firmly established that high blood pressure is associated with an increased risk of renal failure independent of other risk factors. Hypertension-related renal injury might be interpreted in a general context taking into account genes, intrauterine growth and environmental factors. Disturbed intrauterine growth (due to malnutrition or other factors) has a negative influence on the development of the cardiovascular system and favours the occurrence of hypertension, insulin resistance, hypercholesterolaemia and hyperuricaemia in adult life (Barker's hypothesis). Altered intrauterine growth has also been associated with a reduced number of nephrons at birth. Damage attributable to glomerular hyperperfusion in kidneys with a reduced number of nephrons is aggravated by vascular lesions in middle and small arterial vessels (secondary to hypertension, hyperlipidaemia and environmental risk factors such as smoking). The observation that subjects homozygous for the D allele of the ACE gene are predisposed to both cardiovascular complications and nephrosclerosis, suggests that genetic factors may interact with altered intrauterine growth in determining the risk of cardiovascular and renal diseases.

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

    PubMed

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

    2011-01-01

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

  2. Modern Age Pathology of Pulmonary Arterial Hypertension

    PubMed Central

    Stacher, Elvira; Graham, Brian B.; Hunt, James M.; Gandjeva, Aneta; Groshong, Steve D.; McLaughlin, Vallerie V.; Jessup, Marsha; Grizzle, William E.; Aldred, Michaela A.; Cool, Carlyne D.

    2012-01-01

    Rationale: The impact of modern treatments of pulmonary arterial hypertension (PAH) on pulmonary vascular pathology remains unknown. Objectives: To assess the spectrum of pulmonary vascular remodeling in the modern era of PAH medication. Methods: Assessment of pulmonary vascular remodeling and inflammation in 62 PAH and 28 control explanted lungs systematically sampled. Measurements and Main Results: Intima and intima plus media fractional thicknesses of pulmonary arteries were increased in the PAH group versus the control lungs and correlated with pulmonary hemodynamic measurements. Despite a high variability of morphological measurements within a given PAH lung and among all PAH lungs, distinct pathological subphenotypes were detected in cohorts of PAH lungs. These included a subset of lungs lacking intima or, most prominently, media remodeling, which had similar numbers of profiles of plexiform lesions as those in lungs with more pronounced remodeling. Marked perivascular inflammation was present in a high number of PAH lungs and correlated with intima plus media remodeling. The number of profiles of plexiform lesions was significantly lower in lungs of male patients and those never treated with prostacyclin or its analogs. Conclusions: Our results indicate that multiple features of pulmonary vascular remodeling are present in patients treated with modern PAH therapies. Perivascular inflammation may have an important role in the processes of vascular remodeling, all of which may ultimately lead to increased pulmonary artery pressure. Moreover, our study provides a framework to interpret and design translational studies in PAH. PMID:22679007

  3. Modern age pathology of pulmonary arterial hypertension.

    PubMed

    Stacher, Elvira; Graham, Brian B; Hunt, James M; Gandjeva, Aneta; Groshong, Steve D; McLaughlin, Vallerie V; Jessup, Marsha; Grizzle, William E; Aldred, Michaela A; Cool, Carlyne D; Tuder, Rubin M

    2012-08-01

    The impact of modern treatments of pulmonary arterial hypertension (PAH) on pulmonary vascular pathology remains unknown. To assess the spectrum of pulmonary vascular remodeling in the modern era of PAH medication. Assessment of pulmonary vascular remodeling and inflammation in 62 PAH and 28 control explanted lungs systematically sampled. Intima and intima plus media fractional thicknesses of pulmonary arteries were increased in the PAH group versus the control lungs and correlated with pulmonary hemodynamic measurements. Despite a high variability of morphological measurements within a given PAH lung and among all PAH lungs, distinct pathological subphenotypes were detected in cohorts of PAH lungs. These included a subset of lungs lacking intima or, most prominently, media remodeling, which had similar numbers of profiles of plexiform lesions as those in lungs with more pronounced remodeling. Marked perivascular inflammation was present in a high number of PAH lungs and correlated with intima plus media remodeling. The number of profiles of plexiform lesions was significantly lower in lungs of male patients and those never treated with prostacyclin or its analogs. Our results indicate that multiple features of pulmonary vascular remodeling are present in patients treated with modern PAH therapies. Perivascular inflammation may have an important role in the processes of vascular remodeling, all of which may ultimately lead to increased pulmonary artery pressure. Moreover, our study provides a framework to interpret and design translational studies in PAH.

  4. Mitochondrial Dynamics in Pulmonary Arterial Hypertension

    PubMed Central

    Ryan, John; Dasgupta, Asish; Huston, Jessica; Chen, Kuang-Huieh; Archer, Stephen L.

    2015-01-01

    Pulmonary arterial hypertension (PAH) is an idiopathic cardiopulmonary disease characterized by obstruction of small pulmonary arteries by excessive proliferation and apoptosis-resistance of vascular cells, as well as inflammation, thrombosis and vasoconstriction. Vascular obstruction increases the afterload faced by the right ventricle (RV), leading to RV failure. The proliferative, obstructive vasculopathy of PAH shares several mitochondrial abnormalities with cancer, notably a shift to aerobic glycolysis and mitochondrial fragmentation. Mitochondria in the pulmonary artery smooth muscle cell (PASMC) normally serve as oxygen sensors. In PAH, acquired mitochondrial abnormalities, including epigenetic silencing of superoxide dismutase (SOD2), disrupt oxygen sensing creating a pseudo-hypoxic environment characterized by normoxic activation of Hypoxia-Inducible Factor-1α (HIF-1α). The resulting metabolic shift to aerobic glycolysis (the Warburg phenomenon) reflects inhibition of pyruvate dehydrogenase by pyruvate dehydrogenase kinases. In addition, altered mitochondrial dynamics result in mitochondrial fragmentation. The molecular basis of this structural change includes upregulation and activation of fission mediators, notably dynamin-related protein 1 (DRP-1), and downregulation of fusion mediators, especially mitofusin-2 (MFN2). These pathogenic mitochondrial abnormalities offer new therapeutic targets. Inhibition of mitotic fission or enhancement of fusion in PAH PASMC slows cell proliferation, causes cell cycle arrest, and induces apoptosis. DRP-1 inhibition or MFN2 gene therapy can regress PAH in experimental models of PAH. This review focuses on the etiology of mitochondrial fragmentation in PAH and explores the therapeutic implications of mitochondrial dynamics in the pulmonary vasculature and RV. PMID:25672499

  5. Berry splenic artery aneurysm rupture in association with segmental arterial mediolysis and portal hypertension.

    PubMed

    Imai, Miwa Akasofu; Kawahara, Ei; Katsuda, Shogo; Yamashita, Tatsuya

    2005-05-01

    A rare case of berry splenic artery aneurysm (SAA) rupture associated with segmental arterial mediolysis (SAM) and portal hypertension is reported. A 66-year-old woman, diagnosed as having liver cirrhosis and portal hypertension 6 years earlier, suddenly developed a lancinating pain in the upper abdomen and lost consciousness. She recovered consciousness while being transferred to hospital by ambulance. During the investigations, her level of consciousness suddenly deteriorated. Ultrasonography showed a massive intraperitoneal hemorrhage, and she died 5(1/2) h after admission. On gross examination at autopsy it was not possible to find the rupture point of the vessel because the pancreas was embedded in a massive hematoma. However, careful dissection of the pancreatic tail after fixation revealed a berry aneurysm measuring 0.8 cm in diameter in a branch adjacent to the bifurcation in the distal third of the main splenic artery. Microscopic examination detected a rupture of the aneurysm. The histology of the arterial wall proximal to the aneurysm showed typical SAM. In general, berry SAA caused by SAM is rare and unlikely to rupture. The SAA in the present case likely occurred and ruptured due to the combination of SAM and portal hypertension.

  6. Treatment of idiopathic/hereditary pulmonary arterial hypertension.

    PubMed

    Matsubara, Hiromi; Ogawa, Aiko

    2014-10-01

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

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

    PubMed

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

    1983-06-01

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

  8. Arterial Hypertension Aggravates Innate Immune Responses after Experimental Stroke

    PubMed Central

    Möller, Karoline; Pösel, Claudia; Kranz, Alexander; Schulz, Isabell; Scheibe, Johanna; Didwischus, Nadine; Boltze, Johannes; Weise, Gesa; Wagner, Daniel-Christoph

    2015-01-01

    Arterial hypertension is not only the leading risk factor for stroke, but also attributes 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 (SHRs) and normotensive Wistar Kyoto rats (WKYs) were subjected to photothrombotic stroke. One and 3 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 were analyzed by flow cytometry, quantitative real-time PCR and immunohistochemistry in rat brains 4 days after stroke. Although comparable at day 1, lesion volumes were significantly larger in SHR at day 3. 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 finally be responsible for

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

    PubMed

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

    2016-08-01

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

  10. Hypertension and arterial stiffness in heart transplantation patients

    PubMed Central

    de Souza-Neto, João David; de Oliveira, Ítalo Martins; Lima-Rocha, Hermano Alexandre; Oliveira-Lima, José Wellington; Bacal, Fernando

    2016-01-01

    OBJECTIVES: Post-transplantation hypertension is prevalent and is associated with increased cardiovascular morbidity and subsequent graft dysfunction. The present study aimed to identify the factors associated with arterial stiffness as measured by the ambulatory arterial stiffness index. METHODS: The current study used a prospective, observational, analytical design to evaluate a group of adult heart transplantation patients. Arterial stiffness was obtained by monitoring ambulatory blood pressure and using the ambulatory arterial stiffness index as the surrogate outcome. Multivariate logistic regression analyses were performed to control confounding. RESULTS: In a group of 85 adult heart transplantation patients, hypertension was independently associated with arterial stiffness (OR 4.98, CI 95% 1.06-23.4) as well as systolic and diastolic blood pressure averages and nighttime descent. CONCLUSIONS: Measurement of ambulatory arterial stiffness index is a new, non-invasive method that is easy to perform, may contribute to better defining arterial stiffness prognosis and is associated with hypertension. PMID:27652829

  11. The evolving definition of systemic arterial hypertension.

    PubMed

    Ram, C Venkata S; Giles, Thomas D

    2010-05-01

    Systemic hypertension is an important risk factor for premature cardiovascular disease. Hypertension also contributes to excessive morbidity and mortality. Whereas excellent therapeutic options are available to treat hypertension, there is an unsettled issue about the very definition of hypertension. At what level of blood pressure should we treat hypertension? Does the definition of hypertension change in the presence of co-morbid conditions? This article covers in detail the evolving concepts in the diagnosis and management of hypertension.

  12. Fatal hemoperitoneum due to segmental arterial mediolysis

    PubMed Central

    de Campos, Fernando Peixoto Ferraz; Martinês, João Augusto dos Santos

    2016-01-01

    Spontaneous hemoperitoneum due to vascular injury is a life-threatening condition mostly associated with aortic or splanchnic arterial disease, which stems from atherosclerotic, inflammatory, or infectious origin. However, in 1976, Slavin and Gonzales described a nonatherosclerotic arterial disease that may render aneurysmal formation predominantly in the splanchnic arterial bed. The clinical presentation is diverse, but abdominal pain and shock prevail. We report the case of a middle-aged man who presented a hemoperitoneum due to a middle colic artery aneurysm rupture and died after undergoing a surgical treatment attempt. The preoperative imaging study revealed the presence of a huge hematoma in the epiplon retrocavity, and abdominal free liquid as well as extensive arterial disease with multiple aneurysms. The autopsy findings included hemoperitoneum, hematoma in the upper left abdominal quadrant, the surgical ligature of the middle colic artery, and histologic features consistent with segmental arterial mediolysis. The authors call attention to this rare entity and highlight the autopsy as a fundamental examination to accurately reach this diagnosis. PMID:27818953

  13. Fatal hemoperitoneum due to segmental arterial mediolysis.

    PubMed

    Felipe-Silva, Aloísio; de Campos, Fernando Peixoto Ferraz; Martinês, João Augusto Dos Santos

    2016-01-01

    Spontaneous hemoperitoneum due to vascular injury is a life-threatening condition mostly associated with aortic or splanchnic arterial disease, which stems from atherosclerotic, inflammatory, or infectious origin. However, in 1976, Slavin and Gonzales described a nonatherosclerotic arterial disease that may render aneurysmal formation predominantly in the splanchnic arterial bed. The clinical presentation is diverse, but abdominal pain and shock prevail. We report the case of a middle-aged man who presented a hemoperitoneum due to a middle colic artery aneurysm rupture and died after undergoing a surgical treatment attempt. The preoperative imaging study revealed the presence of a huge hematoma in the epiplon retrocavity, and abdominal free liquid as well as extensive arterial disease with multiple aneurysms. The autopsy findings included hemoperitoneum, hematoma in the upper left abdominal quadrant, the surgical ligature of the middle colic artery, and histologic features consistent with segmental arterial mediolysis. The authors call attention to this rare entity and highlight the autopsy as a fundamental examination to accurately reach this diagnosis.

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

    PubMed

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

    2013-01-01

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

  15. Sildenafil in pediatric pulmonary arterial hypertension.

    PubMed

    Dhariwal, A K; Bavdekar, S B

    2015-01-01

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

  16. Sildenafil in pediatric pulmonary arterial hypertension

    PubMed Central

    Dhariwal, AK; Bavdekar, SB

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease of varied etiologies. Although PAH has no curative treatment, a greater understanding of pathophysiology, technological advances resulting in early diagnosis, and the availability of several newer drugs have improved the outlook for patients with PAH. Sildenafil is one of the therapeutic agents used extensively in the treatment of PAH in children, as an off-label drug. In 2012, the United States Food and Drug Administration (USFDA) issued a warning regarding the of use high-dose sildenafil in children with PAH. This has led to a peculiar situation where there is a paucity of approved therapies for the management of PAH in children and the use of the most extensively used drug being discouraged by the regulator. This article provides a review of the use of sildenafil in the treatment of PAH in children. PMID:26119438

  17. [Segmental arterial mediolysis and renovascular hypertension].

    PubMed

    Gaud, Simon; Cridlig, Joelle; Claudon, Michel; Diarrassouba, Assetou; Kessler, Michèle; Frimat, Luc

    2010-12-01

    Segmental arterial mediolysis (SAM) is a rare nonarteriosclerotic, noninflammatory vascular disease of unknown origin that causes vascular occlusion or massive life-threatening intraabdominal hemorrhages. SAM is an acute disease. The initial injurious phase consist in mediolysis, then evolves in chronic vascular lesions. Diagnostic criteria are histologic, but rarely accessible apart from surgical complications. To our knowledge, there is no recommendation concerning therapy and follow-up of these patients. In our patient, we were interested in the atypical clinical presentation with renovascular hypertension, and the coexistence of acute and chronic vascular lesions that suppose the existence of recurrences in the evolution of this disease. We are interested also in the link that might exist between renal infarct and SAM, SAM's chronic vascular lesions and fibromuscular dysplasia vascular lesions.

  18. [Pulmonary arterial hypertension in connective tissue diseases].

    PubMed

    Cordier, Jean-François

    2009-11-01

    Among connective tissue diseases, pulmonary arterial hypertension (PAH) is frequently associated with systemic sclerosis and systemic lupus erythematosus. PAH is less common in mixed connective tissue diseases and Sjögren's syndrome, and rare in rheumatoid arthritis. PAH in systemic sclerosis may be either isolated (prevalence about 8%) or associated with interstitial lung disease. Echocardiographic screening for PAH is worthwhile in patients with systemic sclerosis, especially as treatments for idiopathic PAH (endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostanoids) are effective in this setting. The prevalence of PAH among patients with systemic lupus erythematosus is poorly known; immunosuppressive treatment is sometimes effective by itself but most patients benefit from PAH treatment. PAH associated with connective tissue diseases has a worse prognosis than idiopathic PAH.

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

    PubMed

    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.

  20. Pulmonary arterial hypertension: epidemiology and registries.

    PubMed

    McGoon, Michael D; Benza, Raymond L; Escribano-Subias, Pilar; Jiang, Xin; Miller, Dave P; Peacock, Andrew J; Pepke-Zaba, Joanna; Pulido, Tomas; Rich, Stuart; Rosenkranz, Stephan; Suissa, Samy; Humbert, Marc

    2013-12-24

    Registries of patients with pulmonary arterial hypertension (PAH) have been instrumental in characterizing the presentation and natural history of the disease and provide a basis for prognostication. Since the initial accumulation of data conducted in the 1980s, subsequent registry databases have yielded information about the demographic factors, treatment, and survival of patients and have permitted comparisons between populations in different eras and environments. Inclusion of patients with all subtypes of PAH has also allowed comparisons of these subpopulations. We describe herein the basic methodology by which PAH registries have been conducted, review key insights provided by registries, summarize issues related to interpretation and comparison of the results, and discuss the utility of data to predict survival outcomes. Potential sources of bias, particularly related to the inclusion of incident and/or prevalent patients and missing data, are addressed. A fundamental observation of current registries is that survival in the modern treatment era has improved compared with that observed previously and that outcomes among PAH subpopulations vary substantially. Continuing systematic clinical surveillance of PAH will be important as treatment evolves and as understanding of mechanisms advance. Considerations for future directions of registry studies include enrollment of a broader population of patients with pulmonary hypertension of all clinical types and severity and continued globalization and collaboration of registry databases. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

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

  2. Arterial pulmonary hypertension in noncardiac intensive care unit

    PubMed Central

    Tsapenko, Mykola V; Tsapenko, Arseniy V; Comfere, Thomas BO; Mour, Girish K; Mankad, Sunil V; Gajic, Ognjen

    2008-01-01

    Pulmonary artery pressure elevation complicates the course of many complex disorders treated in a noncardiac intensive care unit. Acute pulmonary hypertension, however, remains underdiagnosed and its treatment frequently begins only after serious complications have developed. Significant pathophysiologic differences between acute and chronic pulmonary hypertension make current classification and treatment recommendations for chronic pulmonary hypertension barely applicable to acute pulmonary hypertension. In order to clarify the terminology of acute pulmonary hypertension and distinguish it from chronic pulmonary hypertension, we provide a classification of acute pulmonary hypertension according to underlying pathophysiologic mechanisms, clinical features, natural history, and response to treatment. Based on available data, therapy of acute arterial pulmonary hypertension should generally be aimed at acutely relieving right ventricular (RV) pressure overload and preventing RV dysfunction. Cases of severe acute pulmonary hypertension complicated by RV failure and systemic arterial hypotension are real clinical challenges requiring tight hemodynamic monitoring and aggressive treatment including combinations of pulmonary vasodilators, inotropic agents and systemic arterial vasoconstrictors. The choice of vasopressor and inotropes in patients with acute pulmonary hypertension should take into consideration their effects on vascular resistance and cardiac output when used alone or in combinations with other agents, and must be individualized based on patient response. PMID:19183752

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

    PubMed Central

    Ataya, Ali; Cope, Jessica; Alnuaimat, Hassan

    2016-01-01

    Significant advances in the understanding of the pathophysiology of pulmonary arterial hypertension over the past two decades have led to the development of targeted therapies and improved patient outcomes. Currently, a broad armamentarium of pulmonary arterial hypertension-specific drugs exists to assist in the treatment of this complex disease state. In this manuscript, we provide a comprehensive review of the current Food and Drug Administration (FDA)-approved pulmonary arterial hypertension-specific therapies, and their supporting evidence for adults, targeting the nitric oxide, soluble guanylate cyclase, endothelin, and prostacyclin pathways. PMID:27929408

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

    PubMed

    Ataya, Ali; Cope, Jessica; Alnuaimat, Hassan

    2016-12-06

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

  5. [Cerebral lesions in acute arterial hypertension: the characteristic MRI in hypertensive encephalopathy].

    PubMed

    Schneider, J P; Krohmer, S; Günther, A; Zimmer, C

    2006-06-01

    In the nine years since the posterior reversible (leuc) encephalopathy syndrome (PRES) was first described, a number of causes have been under discussion. These not only include arterial hypertension, i. e. hypertensive crises, but also various toxic substances, i. e. immunosuppressive or chemotherapeutic agents, that are responsible for the formation of the symptoms and characteristic MR tomographic brain findings. Initial and follow-up MRI examinations of 8 patients were analyzed. All patients had acute neurological symptoms (headaches, seizures, visual disorders and vigilance disturbances) together with a detectable hypertensive crisis. MRI disclosed increased signal intensity in subcortical and some cortical lesions in all patient FLAIR sequences. These changes were particularly extensive in the posterior circulation (occipital, cerebellum and brain stem) although they were also detected in brain areas supplied by the carotid artery. However, a cytotoxic genesis of the changes was ruled out in each patient by means of a normal DWI. Furthermore, when the blood pressure was normalized, reversibility of the lesions as proof of the diagnosis was detectable. The imaging findings can be typically analyzed as a predominantly posterior distribution of encephalopathic lesions with a high probability of reversibility after lowering blood pressure was patients suffering from a critical increase in blood pressure with corresponding neurological symptoms. The exact pathophysiology remains unclear, but the cause currently most favored is a vasculopathy of the posterior circulation due to diminished adrenergic autoregulation in combination with a dysfunction of the endothelial cells. In conclusion, we suggest designating this subpopulation from the non-uniform pool of patients with posterior (leuc) encephalopathy as "hypertensive encephalopathy". "Hypertensive encephalopathy" has to be distinguished from "toxic encephalopathy", particularly due to different therapeutic and

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

    PubMed

    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.

  7. Recapitulation of developing artery muscularization in pulmonary hypertension.

    PubMed

    Sheikh, Abdul Q; Lighthouse, Janet K; Greif, Daniel M

    2014-03-13

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

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

    PubMed

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

    2017-01-01

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

  9. [Arterial hypertension and obesity--a dangerous combination].

    PubMed

    Zakharieva, S

    1999-01-01

    The combination of obesity with arterial hypertension is frequent finding in clinical practice. In 70% of the males and 61% of the females the high blood pressure is directly connected with obesity. The assumed mechanisms by which obesity leads to arterial hypertension are: insuline resistance; genetic factors (hypothesis for the sparing gene); correlations leptin-neuropeptide Y; fatty tissue as origin of local pressor and depressor humoral factors. The arterial hypertension in obesity is salt-sensible, associated with increased intraglomerular pressure, microalbuminuria and increased risk for cardiovascular complications. The reduction of the body weight is the principal nonmedical mean for treatment of the arterial hypertension. Of the antihypertensive drugs those which are neutral with respect to the carbohydrat and fat metabolism are preferred inhibitors of the converting enzyme, calcium antagonists, selective alpha-1 blockers, central alpha-2 agonist.

  10. Prostanoid therapy for pulmonary arterial hypertension.

    PubMed

    Badesch, David B; McLaughlin, Vallerie V; Delcroix, Marion; Vizza, Carmine Dario; Olschewski, Horst; Sitbon, Olivier; Barst, Robyn J

    2004-06-16

    Prostanoids have played a prominent role in the treatment of pulmonary arterial hypertension (PAH). Several compounds and methods of administration have been studied: chronic intravenously infused epoprostenol, chronic subcutaneously infused treprostinil, inhaled iloprost, and oral beraprost. Chronic intravenous epoprostenol therapy has had a substantial impact on the clinical management of patients with severe PAH. It improves exercise capacity, hemodynamics, and survival in patients with idiopathic pulmonary arterial hypertension (IPAH). It also improves exercise capacity and hemodynamics in patients with PAH occurring in association with scleroderma. The complexity of epoprostenol therapy (chronic indwelling catheters, reconstitution of the drug, operation of the infusion pump, and others) has led to attempts to develop other prostanoids with simpler modes of delivery. Treprostinil, a stable prostacyclin analogue with a half-life of 3 h, has been developed for subcutaneous delivery. It has beneficial effects on exercise and hemodynamics, which depend somewhat on the dose achieved. This, in turn, is determined by the patient's ability to tolerate the drug's side effects, including pain and erythema at the infusion site. Inhaled iloprost therapy may provide selectivity of the hemodynamic effects to the lung vasculature, thus avoiding systemic side effects. In a randomized and controlled trial, iloprost resulted in improvement in a combined end point incorporating the New York Heart Association functional class, 6-min walk test, and deterioration or death. Beraprost is the first orally active prostacyclin analogue. In the first of two randomized controlled trials, beraprost increased exercise capacity in patients with IPAH, with no significant changes in subjects with associated conditions. Hemodynamics did not change significantly, and no difference in survival was detected between the two treatment groups. The second study showed that beraprost-treated patients

  11. Pulmonary arterial hypertension associated with impaired lysosomal endothelin-1 degradation.

    PubMed

    Recla, Sabine; Hahn, Andreas; Apitz, Christian

    2015-04-01

    We report on a boy with severe pulmonary arterial hypertension associated with mucolipidosis, a rare lysosomal storage disorder. During diagnostic catheterisation, we found increased endothelin-1 levels, but normal big endothelin-1-levels (the precursor form of endothelin-1), which suggests impaired degradation of endothelin-1 rather than increased synthesis. As endothelin-1 degradation takes place in the lysosome, it appears likely that lysosomal dysfunction caused by the underlying disease contributes to the development of pulmonary arterial hypertension in this patient.

  12. The metabolic theory of pulmonary arterial hypertension.

    PubMed

    Paulin, Roxane; Michelakis, Evangelos D

    2014-06-20

    Numerous molecular abnormalities have been described in pulmonary arterial hypertension (PAH), complicating the translation of candidate therapies to patients because, typically, 1 treatment addresses only 1 abnormality. The realization that in addition to pulmonary artery vascular cells, other tissues and cells are involved in the syndrome of PAH (eg, immune cells, right ventricular cardiomyocytes, skeletal muscle) further complicates the identification of optimal therapeutic targets. Here, we describe a metabolic theory that proposes that many apparently unrelated molecular abnormalities in PAH do have a common denominator; they either cause or promote a mitochondrial suppression (inhibition of glucose oxidation) in pulmonary vascular cells; in turn, the signaling downstream from this mitochondrial suppression can also explain numerous molecular events previously not connected. This integration of signals upstream and downstream of mitochondria has similarities to cancer and can explain many features of the PAH vascular phenotype, including proliferation and apoptosis resistance. This suppression of glucose oxidation (with secondary upregulation of glycolysis) also underlies the abnormalities in extrapulmonary tissues, suggesting a global metabolic disturbance. The metabolic theory places mitochondria at the center stage for our understanding of PAH pathogenesis and for the development of novel diagnostic and therapeutic tools. Current PAH therapies are each addressing 1 abnormality (eg, upregulation of endothelin-1) and were not developed specifically for PAH but for systemic vascular diseases. Compared with the available therapies, mitochondria-targeting therapies have the advantage of addressing multiple molecular abnormalities simultaneously (thus being potentially more effective) and achieving higher specificity because they address PAH-specific biology. © 2014 American Heart Association, Inc.

  13. Hemodynamics and arterial properties in response to mental stress in individuals with mild hypertension.

    PubMed

    Tsai, Pei-Shan; Yucha, Carolyn B; Nichols, Wilmer W; Yarandi, Hossein

    2003-01-01

    The role of tonic sympathetic stimulation on the properties of large arteries is largely unknown. The purpose of this study was to determine the effect of mental stress on hemodynamics and arterial properties in mild hypertensives. Twenty-three subjects with mild hypertension and 19 age-matched normotensives were compared to examine changes in hemodynamics and central arterial wave reflection before, during, and after mental stress. The results demonstrate an acute effect of mental stress on blood pressure, heart rate, and arterial compliance. The static component (MBP) and the pulsatile (PP) component of arterial pressure increased significantly during mental stress and returned to baseline within a few minutes. Mild hypertensives did not have an increased response to mental stress. For both groups, an increase in HR and a consequent rise in CO were responsible for the increase in BP in response to mental stress. Compared with baseline, both groups demonstrated a decrease in arterial compliance during stress. Mental stress did not induce a significant change in total peripheral vascular resistance nor did it affect central arterial wave reflection in both groups. Individuals with mild hypertension demonstrated higher PP (p <.001), lower arterial compliance (p <.01), and higher AI (p <.05) than those with normal BP. Hemodynamic and arterial responses to mental stress in individuals with normal BP and mild hypertension were similar. Several parameters, however, were different in basal state. These differences (ie, higher PP, lower compliance, and higher AI in the mild hypertensive group) could be due to the chronic effect of sympathetic stimulation on central arteries.

  14. [Systemic arterial hypertension in child and adolescent].

    PubMed

    Rosas-Peralta, Martín; Medina-Concebida, Luz Elena; Borrayo-Sánchez, Gabriela; Madrid-Miller, Alejandra; Ramírez-Arias, Erick; Pérez-Rodríguez, Gilberto

    2016-01-01

    The epidemic of childhood obesity, the risk of developing left ventricular hypertrophy, and evidence of the early development of atherosclerosis in children would make the detection of and intervention in childhood hypertension important to reduce long-term health risks; however, supporting data are lacking. Secondary hypertension is more common in preadolescent children, with most cases caused by renal disease. Primary or essential hypertension is more common in adolescents and has multiple risk factors, including obesity and a family history of hypertension. Evaluation involves a through history and physical examination, laboratory tests, and specialized studies. Management is multifaceted. Nonpharmacologic treatments include weight reduction, exercise, and dietary modifications. Although the evidence of first line therapy for hypertension is still controversial, the recommendations for pharmacologic treatment are based on symptomatic hypertension, evidence of end-organ damage, stage 2 of hypertension, or stage 1 of hypertension unresponsive to lifestyle modifications, and hypertension with diabetes mellitus where is the search for microalbuminuria justified.

  15. Family caregiving in pulmonary arterial hypertension.

    PubMed

    Hwang, Boyoung; Howie-Esquivel, Jill; Fleischmann, Kirsten E; Stotts, Nancy A; Dracup, Kathleen

    2012-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease that places a significant burden on patients and their families. However, family caregiving, to the best of our knowledge, has never been described in this population. This study sought to describe depressive symptoms, types of performed care tasks, social support, and the impact of caregiving among family caregivers of patients with PAH. Data were obtained from 35 dyads of patients with PAH (mean age, 51 years; 63% were female; 54% had World Health Organization functional class III symptoms) and their family caregivers (mean age, 52 years; 60% were female; 68% were spouses). Five caregivers (14%) were identified as manifesting moderate to severe depressive symptoms. The majority of caregivers reported that their daily activities were centered around caregiving responsibilities. More than 85% of caregivers were involved in managing care for the patient, and more than half helped the patient with self-management activities. The level of caregivers' perceived social support was low, especially for emotional and informational support. Lower levels of social support were significantly associated with more severe depressive symptoms in caregivers (r = -.50, P = .002). Caregivers of patients with PAH play a significant role in patients' medical care and self-management, yet they lack sufficient emotional support or information to meet the demands of caregiving. These findings underscore the importance of supporting family caregivers of patients with PAH. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Association of Parental Hypertension with Arterial Stiffness in Non-Hypertensive Offspring: The Framingham Heart Study

    PubMed Central

    Andersson, Charlotte; Quiroz, Rene; Enserro, Danielle; Larson, Martin G.; Hamburg, Naomi M.; Vita, Joseph A.; Levy, Daniel; Benjamin, Emelia J.; Mitchell, Gary F.; Vasan, Ramachandran S.

    2016-01-01

    High arterial stiffness appears to be causally involved in the pathogenesis of hypertension. We tested the hypothesis that offspring of parents with hypertension may display higher arterial stiffness prior to clinically manifest hypertension, given that hypertension is a heritable condition. We compared arterial tonometry measures in a sample of 1564 non-hypertensive Framingham Heart Study Third generation cohort participants (mean age 38 years, 55% women) whose parents were enrolled in the Framingham Offspring Study. A totally of 468, 715, and 381 participants had 0 (referent), 1, and 2 parents with hypertension. Parental hypertension was associated with greater offspring mean arterial pressure (multivariable-adjusted estimate= 2.9 mm Hg, 95% confidence interval [CI] 1.9-3.9, and 4.2 mm Hg, 95% CI 2.9-5.5, for 1 and 2 parents with hypertension, respectively, p<0.001 for both), and with greater forward pressure wave amplitude (1.6 mm Hg, 95% CI 0.6-2.7, and 1.9 mm Hg, 95% CI 0.6-3.2, for 1 and 2 parents with hypertension, respectively, p=0.003 for both). Carotid-femoral pulse wave velocity and augmentation index displayed similar dose-dependent relations with parental hypertension in sex, age, and height-adjusted models, but associations were attenuated upon further adjustment. Offspring with at least one parent in the upper quartile of augmentation index and carotid-femoral pulse wave velocity had significantly higher values themselves (p≤0.02). In conclusion, in this community-based sample of young, non-hypertensive adults, we observed greater arterial stiffness in offspring of parents with hypertension. These observations are consistent with higher vascular stiffness at an early stage in the pathogenesis of hypertension. PMID:27456526

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

    PubMed

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

    2015-10-01

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

  18. Pulmonary hypertension due to acute respiratory distress syndrome

    PubMed Central

    Ñamendys-Silva, S.A.; Santos-Martínez, L.E.; Pulido, T.; Rivero-Sigarroa, E.; Baltazar-Torres, J.A.; Domínguez-Cherit, G.; Sandoval, J.

    2014-01-01

    Our aims were to describe the prevalence of pulmonary hypertension in patients with acute respiratory distress syndrome (ARDS), to characterize their hemodynamic cardiopulmonary profiles, and to correlate these parameters with outcome. All consecutive patients over 16 years of age who were in the intensive care unit with a diagnosis of ARDS and an in situ pulmonary artery catheter for hemodynamic monitoring were studied. Pulmonary hypertension was diagnosed when the mean pulmonary artery pressure was >25 mmHg at rest with a pulmonary artery occlusion pressure or left atrial pressure <15 mmHg. During the study period, 30 of 402 critically ill patients (7.46%) who were admitted to the ICU fulfilled the criteria for ARDS. Of the 30 patients with ARDS, 14 met the criteria for pulmonary hypertension, a prevalence of 46.6% (95% CI; 28-66%). The most common cause of ARDS was pneumonia (56.3%). The overall mortality was 36.6% and was similar in patients with and without pulmonary hypertension. Differences in patients' hemodynamic profiles were influenced by the presence of pulmonary hypertension. The levels of positive end-expiratory pressure and peak pressure were higher in patients with pulmonary hypertension, and the PaCO2 was higher in those who died. The level of airway pressure seemed to influence the onset of pulmonary hypertension. Survival was determined by the severity of organ failure at admission to the intensive care unit. PMID:25118626

  19. Pulmonary arterial hypertension in idiopathic inflammatory myopathies

    PubMed Central

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

    2016-01-01

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

  20. Relationships between coronary flow vasodilator capacity and small artery remodelling in hypertensive patients.

    PubMed

    Rizzoni, Damiano; Palombo, Carlo; Porteri, Enzo; Muiesan, Maria Lorenza; Kozàkovà, Michaela; La Canna, Giovanni; Nardi, Matilde; Guelfi, Daniele; Salvetti, Massimo; Morizzo, Carmela; Vittone, Francesca; Rosei, Enrico Agabiti

    2003-03-01

    Arterial hypertension is frequently associated with the presence of structural alterations in small arteries. Moreover, a reduced coronary flow reserve and vasodilator capacity has been observed in essential hypertensive patients, possibly due, at least in part, to microangiopathy of small coronary vessels. The aim of the present study was to evaluate a possible relationship between subcutaneous small artery structure and coronary flow reserve or vasodilator capacity in patients with essential hypertension. A total of 20 patients with mild to moderate essential hypertension were included in the study, and underwent a biopsy of the subcutaneous fat from the gluteal region. Small arteries were dissected and mounted on a micromyograph. The media thickness, the normalized internal diameter and the media:lumen ratio (M/L) were then calculated. In addition, a transesophageal Doppler echocardiographic study, which allows the measurement of coronary flow velocity before and during maximal pharmacological vasodilatation, was performed. Coronary flow reserve (CFR) was measured as the ratio of coronary flow velocity assessed during adenosine infusion and that measured in basal conditions. From blood pressure and coronary flow velocity during adenosine infusion, minimum coronary resistance was calculated. CFR as well as minimum coronary resistance were significantly correlated to both M/L and to normalized internal diameter of subcutaneous small arteries. Our results are consistent with the hypothesis of a generalized remodelling of small arteries in the body, including the coronary circulation; this remodelling may play an important role in the reduction of coronary vasodilator capacity in patients with mild to moderate essential hypertension.

  1. Research on red cell membrane permeability in arterial hypertension.

    PubMed

    Gatina, R; Balta, N; Moisin, C; Burtea, C; Botea, S; Ioan, M; Teleianu, C

    1998-01-01

    Arterial hypertension, including the elucidation of hypertension pathogenic mechanisms involving elements in the composition of the blood, continues to represent a topical research area. Recent work, such as nuclear magnetic resonance studies looking into red cell permeability, illustrates the presence of modifications of red cell permeability to water (RCPW) related to the stage of arterial hypertension. The identification of a significant increase of RCPW compared to that present in the population with normal arterial pressure values can be useful both in early diagnosis and in warning about a possible predisposition for this condition. At the same time, the dynamic investigation of protonic relaxation time of both intra- and extra-erythrocytic water, the assessment of proton exchange time across the red cell and the calculation of permeability to water enable one not only to diagnose arterial hypertension but also to ascertain the evolution of the disease, its complications and the effectiveness of anti-hypertensive medication. Our studies have also proven the existence of a correlation between the values of systolic arterial pressure and red cell permeability to water. The curve describing the interdependence of the two values has the shape of a bell, in the case of males. The peak of the curve is reached for a systolic pressure of 160 mmHg and gets below the values of the control group in the case of systolic pressures above 200 mmHg. The RCPW test can also be considered a valuable indicator in evaluating the risk of stroke in hypertensive patients. In the chronic therapy of arterial hypertension with various types of anti-hypertensive drugs, one can note differences in the RCPW values related to the effectiveness of the respective medication, to the clinical form and stage of the disease, the sex of the patient as well as to the existence of cerebro-vascular complications.

  2. Sublingual Microcirculation in Pulmonary Arterial Hypertension

    PubMed Central

    Dababneh, Luma; Cikach, Frank; Alkukhun, Laith; Dweik, Raed A.

    2014-01-01

    Rationale: Pulmonary arterial hypertension (PAH) is a pulmonary vasculopathy that leads to failure of the right ventricle and premature death. Objectives: To determine whether the sublingual microcirculation is affected in patients with PAH compared with healthy age- and sex-matched control subjects. Methods: Using the CapiScope Handheld Video Capillaroscope we measured the sublingual microvasculature density, flow index, tortuosity, and curvature. Videos were acquired immediately after right heart catheterization, and determinations were made off-line by investigators blinded to the group assignment or hemodynamics. Measurements and Main Results: In this cross-sectional pilot study, we included 26 patients with PAH (age, mean ± SD, 56.7 ± 10 yr; 77% women) and 14 healthy control subjects (age, 53.1 ± 12 yr; 71% women). Sublingual microvasculature flow index was lower (2 ± 0.66 vs. 2.7 ± 0.37, P < 0.001) with higher heterogeneity index (0.63 ± 0.63 vs. 0.25 ± 0.25, P = 0.04) in patients with PAH than control subjects. Microvasculature density was similar between the groups, but tortuosity was more pronounced in patients than control subjects (tort 0: 45 ± 19 vs. 23.6 ± 12, P = 0.001 and tort 1: 0.2 ± 0.16 vs. 0.06 ± 0.04, P < 0.001). Conclusions: Patients with PAH showed lower sublingual microvasculature flow index and higher tortuosity compared with healthy age- and sex-matched control subjects. Further investigations are needed to assess whether this methodology can provide information on disease prognosis and/or response to therapy in this condition. PMID:24601682

  3. Genetics and genomics of pulmonary arterial hypertension.

    PubMed

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

    2013-12-24

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

  4. miR-223 reverses experimental pulmonary arterial hypertension.

    PubMed

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

    2015-09-15

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

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

    PubMed

    Rizzoni, Damiano; Agabiti-Rosei, Enrico

    2012-06-01

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

  6. [Arterial hypertension and alcoholism among workers in an oil refinery].

    PubMed

    Lima, C T; Carvalho, F M; Quadros, C de A; Gonçalves, H R; Silva Júnior, J A; Peres, M F; Bonfim, M S

    1999-09-01

    The role of alcohol ingestion in the incidence of arterial hypertension has not been completely established. In addition, there are few studies addressing this point in relation to populations of workers. The objective of this study was to evaluate the association between alcoholism and arterial hypertension among workers in an oil refinery in Mataripe, Bahia, Brazil, from 1986 to 1993. We designed a retrospective cohort study with a 7-year follow-up in a stratified systematic sample of 335 workers from the refinery. Arterial hypertension was diagnosed based on blood pressure measurements done during routine medical examinations. At the beginning of follow-up, three groups were defined using the CAGE test of alcohol dependency: nondrinkers (n = 121), CAGE-negative workers (n = 116), and CAGE-positive workers (n = 98). In comparison with the CAGE-negative group, the CAGE-positive group had both greater relative risk and greater attributable risk for developing arterial hypertension (RR = 2.58; AR = 24.95 per 1,000 person-years). The CAGE-positive group also had greater risks compared to nondrinkers (RR = 2.06; AR = 20.97 per 1,000 person-years). The attributable fractions for the same two comparisons of groups were 61% and 51%, respectively. Rate standardization by age or smoking habit did not substantially change the results. Alcoholism is an important risk factor for arterial hypertension.

  7. Serum lipoprotein (a) levels in patients with arterial hypertension.

    PubMed

    Serban, Corina; Nicola, T; Mateescu, Rodica; Noveanu, Lavinia; Susan, Lelia; Pacurari, Alina; Caraba, A; Romoşan, I; Cristescu, A

    2010-01-01

    Lp(a) is capable of deleteriously altering the balance between the procoagulant and anticoagulant, proinflammatory and anti-inflammatory, and vasorelaxing and vasoconstricting properties of the endothelium. The purpose of this study was to investigate the serum concentration of Lp(a) and the main parameters of lipid profile in three groups of subjects: a control group that included 16 healthy subjects, 20 patients with arterial hypertension and dyslipidemia and 20 patients with arterial hypertension without dyslipidemia. Using B-mode ultrasonography, we evaluated carotid intima-media thickness (IMT) and flow mediated vasodilation (FMD) on brachial artery. We found significant higher Lp(a) concentrations in hypertensive patients with dislipidemia (70 +/- 55.95 mg/dL, p < 0.001) and in hypertensive patients without dislipidemia (69 +/- 52.33 mg/dL, p < 0.001), comparative with the control group (19 +/- 14.64 mg/dL). In hypertensive patients with dislipidemia we found a strong negative correlation between Lp(a) and carotid IMT (R2 = -0.75, p < 0.001) and a moderate negative correlation between Lp(a) and FMD (R2 = -0.38, p < 0.001). Lp(a) level wasn't correlated with the main parameters of lipid profile. These results indicated that serum Lp(a) values could play an important role in essential hypertension pathogenesis and could be considered as an individual risk factor in hypertensive patients.

  8. [Therapeutic complexes of physical factors in mild arterial hypertension].

    PubMed

    Kniazeva, T A; Nikiforova, T I

    2001-01-01

    Three therapeutic complexes were compared clinically in patients with mild arterial hypertension. Complex 1 consisted of dry air--radon baths, bicycle exercise and exposure of the renal projection area to decimetric electromagnetic field. Its efficacy was 90%, mechanism of the hypotensive action is reduction of enhanced activity of the sympathico-adrenal and renin-angiotensin-aldosterone systems, improvement of water-mineral metabolism and lipid peroxidation. Complex 2 consisted of dry effervescent baths, anaprilin electrophoresis with sinusoidal modulated currents and exposure of the renal projection area to low-frequency alternating magnetic field. Its efficacy was 80%. It affects renin-angiotensin-aldosterone system, water-mineral metabolism and lipid peroxidation. Complex 3 consisted of electric sleep, laser therapy and general sodium chloride baths. Its efficacy was 63%. The effect was due to inhibition of high sympathico-adrenal system.

  9. [Azilsartan Medoxomil Capabilities in Arterial Hypertension and Obesity].

    PubMed

    Vasyuk, Y A; Shupenina, E Y; Nesvetov, V V; Nesterova, E A; Golubkova, E I

    2016-12-01

    Arterial hypertension (AH) is one of the most common cardiovascular disease. Angiotensin II (AT II), the hormone of renin-angiotensin-aldosterone system, realizes its negative effects through AT 1 receptors - application point of angiotensin receptor blockers (ARB). Due to different dissociation AT 1 receptors properties some ARBs are more effective than others. Multiply multicenter randomized and observational studies approve the effectiveness and safety of azilsartan medoxomil in patients with AH 1-2 grade. Several preclinical studies have shown the additional properties of azilsartan, including increase of insulin sensitivity, cardio- and nephron protection in obesity. In our clinical case we showed the positive influence of azilsartan medoxomil on clinic and ambulatory blood pressure, 24-hour aortic stiffness parameters, longitudinal left ventricular strain in patient with AH and obesity.

  10. Pulmonary hypertension

    MedlinePlus

    Pulmonary arterial hypertension; Sporadic primary pulmonary hypertension; Familial primary pulmonary hypertension; Idiopathic pulmonary arterial hypertension; Primary pulmonary hypertension; PPH; Secondary pulmonary ...

  11. Norepinephrine release in arteries of spontaneously hypertensive rats

    SciTech Connect

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

    1982-01-01

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

  12. Therapy for Pulmonary Arterial Hypertension Associated with Systemic Sclerosis

    PubMed Central

    Mathai, Stephen C.; Hassoun, Paul M.

    2010-01-01

    Purpose of review Systemic sclerosis is commonly complicated by pulmonary arterial hypertension (PAH-SSc) and is a leading cause of death in this population. We will review existing challenges and recent advances in the treatment of this disease. Recent findings Traditionally employed outcome measures in pulmonary arterial hypertension research may not be applicable in PAH-SSc. Importantly, new therapies that target abnormal cellular proliferation in the pulmonary vasculature are currently under investigation and may be particularly relevant to PAH-SSc. Summary Pulmonary arterial hypertension complicating systemic sclerosis occurs commonly and portends a poor prognosis. However, recent advances in our understanding of the disease in the context of systemic sclerosis may lead to novel diagnostic and therapeutic strategies that will ultimately improve quality of life and survival in this population. PMID:19667994

  13. Management of Sepsis in Patients with Pulmonary Arterial Hypertension in the Intensive Care Unit.

    PubMed

    Tartavoulle, Todd M

    2017-03-01

    Pulmonary arterial hypertension is a lethal condition, and the management of sepsis in patients with pulmonary arterial hypertension is challenging. As the disease progresses, the right ventricle is susceptible to failure due to a high pulmonary vascular resistance. The limited ability of the right ventricle to increase cardiac output in septic shock makes it difficult to deliver oxygen to the organ and tissues. Intravascular volume replacement and vasoactive drugs should only be considered after a thorough assessment. Priorities of care include improving cardiac output and oxygen delivery by optimizing preload, reducing afterload, and improving contractility.

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

    PubMed

    Hadinnapola, Charaka; Pepke-Zaba, Joanna

    2015-10-01

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

  15. Inhaled iloprost for therapy in pulmonary arterial hypertension.

    PubMed

    Ewert, Ralf; Gläser, Sven; Bollmann, Tom; Schäper, Christoph

    2011-04-01

    Iloprost (Ventavis, Bayer Schering Pharma, Germany) is a synthetic prostacyclin that is used in its inhalative form for the therapy of pulmonary arterial hypertension. Long-term therapy can increase exercise capacity and quality of life. The use of modern nebulizers especially designed for the administration of iloprost guarantees the pulmonary deposition of the required doses and systematically minimizes side effects. Regarding existing data, inhalative iloprost acts in effective and safe combination with other classes of medication; indeed, such combination therapy is frequently necessary in pulmonary arterial hypertension.

  16. End points and clinical trial design in pulmonary arterial hypertension.

    PubMed

    McLaughlin, Vallerie V; Badesch, David B; Delcroix, Marion; Fleming, Thomas R; Gaine, Sean P; Galiè, Nazzareno; Gibbs, J Simon R; Kim, Nick H; Oudiz, Ronald J; Peacock, Andrew; Provencher, Steeve; Sitbon, Olivier; Tapson, Victor F; Seeger, Werner

    2009-06-30

    New and emerging therapies might provide benefit in patients with pulmonary arterial hypertension. Their efficacy and safety will be compared with existing combination therapies in randomized clinical trials. Appropriate end points for these trials need to be identified: these will include exercise testing, the composite end point of time to clinical worsening, and hemodynamic markers, including advanced imaging modalities and biomarkers. Quality-of-life questionnaires are useful and important secondary end points; pulmonary arterial hypertension-specific questionnaires are currently being developed. Advantages and disadvantages of various trial designs, including placebo-controlled monotherapy or add-on trials, noninferiority studies, and withdrawal trials are also discussed.

  17. Surrogate and combined end points in pulmonary arterial hypertension.

    PubMed

    Ventetuolo, Corey E; Benza, Raymond L; Peacock, Andrew J; Zamanian, Roham T; Badesch, David B; Kawut, Steven M

    2008-07-15

    Pulmonary arterial hypertension is a rare and often devastating disease, although various effective therapies are now available. Clinical trials have used hemodynamic, cardiac imaging, laboratory, and exercise measurements as surrogate and intermediate end points in pulmonary arterial hypertension. Yet, based on the current literature, it is difficult to surmise which of these (if any) have been definitively validated. In addition, investigators have advocated the use of combined clinical end points in future clinical trials. The dependence of clinical trials and clinical management on such end points warrants a review of their use.

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

    PubMed

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

    2015-08-01

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

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

    PubMed Central

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

    2014-01-01

    Arterial hypertension is a chronic medical condition associated with an elevated blood pressure. Chronic arterial hypertension initiates a series of events, which are known to collectively initiate arterial wall thickening. However, the correlation between macrostructural mechanical loading, microstructural cellular changes, and macrostructural adaptation remains unclear. Here, we present a microstructurally motivated computational model for chronic arterial hypertension through smooth muscle cell growth. To model growth, we adopt a classical concept based on the multiplicative decomposition of the deformation gradient into an elastic part and a growth part. Motivated by clinical observations, we assume that the driving force for growth is the stretch sensed by the smooth muscle cells. We embed our model into a finite element framework, where growth is stored locally as an internal variable. First, to demonstrate the features of our model, we investigate the effects of hypertensive growth in a real human carotid artery. Our results agree nicely with experimental data reported in the literature both qualitatively and quantitatively. PMID:25342868

  20. [Impact of an active educational strategy in arterial hypertension].

    PubMed

    Peredo Rosado, Pedro; Gómez López, Victor Manuel; Sánchez Nuncio, Héctor Rafael; Sánchez Navarrete, Arturo; García Ruiz, Martha Elena

    2005-01-01

    To evaluate the efficacy of an active-participative educational intervention on the average arterial pressure, index of corporal mass and level of knowledge in hypertensive patients. A quasi-experimental open study was carried out. An active-participative educational intervention 4 h daily during a period of 5 days twice monthly for 3 months focused on themes related to arterial hypertension in patients with high blood pressure. No control subjects were included. Subject to acceptance and after informed consent, 48 patients (25-60 years of age) were included with slight and moderate arterial hypertension. Patients with evidence of severe organ damage or with chronic underlying disease were excluded. The impact of the educational intervention was evaluated based on the increase of knowledge, improvement of weight (IMC), and average arterial pressure, taking into consideration 2, 4, and 6 months of the educational strategy. Descriptive statistics were utilized for analyzing results using Student's ttest. The level of knowledge increased 31.30 points in the population studied and there was a decrease of the IMC of 2.75 points after educational intervention (p < 0.05). The decrease in weight, as well as the arterial pressure, showed statistically significant differences with respect to the initial measurements, with a difference of the PAM of 13.69 mm Hg at the conclusion of the study (p < 0.05). An active-participative educational strategy is useful in the control of the PAM and IMC in the hypertensive patient.

  1. Practical considerations for the pharmacotherapy of pulmonary arterial hypertension.

    PubMed

    Bishop, Bryan M; Mauro, Vincent F; Khouri, Samer J

    2012-09-01

    Pulmonary arterial hypertension is a devastating disease. Before the 1990s, when pharmacologic treatment was finally approved, only supportive therapy was available, consisting of anticoagulation, digoxin, diuretics, and supplemental oxygen. Calcium channel blocker therapy was also an option, but only a small percentage of patients respond to it. However, starting with epoprostenol in 1996, the number of drugs approved to treat pulmonary arterial hypertension increased. Three distinct classes of drugs were developed based on the pathophysiology of the disease: the prostanoids, endothelin-1 receptor antagonists, and phosphodiesterase type 5 inhibitors. The prostanoids are administered either parenterally or by inhalation to replace the lack of prostacyclin within the pulmonary arterial vasculature. The endothelin-1 receptor antagonists were the first class of oral drugs to be developed, but drug interactions and adverse effects are prominent with this class. The phosphodiesterase type 5 inhibitors increase the second messenger cyclic guanosine monophosphate (GMP) that is induced by nitric oxide stimulation. All of the drugs within these three classes are distinct in and of themselves, and their clinical use requires in-depth knowledge of pulmonary arterial hypertension and its pathophysiology. Because these drugs have different mechanisms of action, combination therapy has shown promise in patients with severe disease, although data are still lacking. This article should serve as a practical guide for clinicians who encounter patients with pulmonary arterial hypertension and the drugs used for the treatment of this devastating disease.

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

    PubMed

    Perros, Frédéric; Dorfmüller, Peter; Humbert, Marc

    2005-08-01

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

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

    PubMed

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

    2016-03-01

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

  4. Elevated vertebrobasilar artery resistance in neonatal spontaneously hypertensive rats.

    PubMed

    Cates, Matthew J; Steed, Peter W; Abdala, Ana P L; Langton, Philip D; Paton, Julian F R

    2011-07-01

    There is a strong correlation between increased vertebral artery resistance and arterial blood pressure in humans. The reasons for this increased resistance at high systemic pressure remain unknown, but may include raised sympathetic activity. With the recent finding that prehypertensive spontaneously hypertensive (PHSH) rats, which have raised sympathetic nerve activity, but a blood pressure comparable to normotensive rat strains, we hypothesized that its vertebrobasilar vascular resistance would already be raised and, as a consequence, would exhibit a more responsive Cushing response (e.g., brain ischemia evoked sympathoexcitation and a pressor response). We report that PHSH rats exhibited a remodeling of the basilar artery (i.e., increased wall thickness and lower lumen-to-wall thickness ratio) that occurred before the onset of hypertension. In a novel in vitro vascularly isolated, arterially perfused brain stem preparation of PHSH rats of 4-5 wk of age, brain stem vascular resistance was raised by ∼35% relative to age- and sex-matched normotensive rats (P < 0.05). In the in situ arterial perfused working heart-brain stem preparation, occlusion of both vertebral arteries in the PHSH rat resulted in a significantly greater increase in sympathetic activity (57 vs. 20%, PHSH vs. control; P < 0.01) that triggered a greater increase in arterial perfusion pressure (8 vs. 3 mmHg, PHSH vs. control; P < 0.01) compared with normotensive rats. These data indicate raised vertebrobasilar artery resistance before the onset of hypertension in the PHSH rat. With the raised responsiveness of the Cushing response in the PHSH rat, we discuss the possibility of brain stem perfusion as a central nervous system determinant of the set point of vasomotor sympathetic tone in the hypertensive condition.

  5. Elevated vertebrobasilar artery resistance in neonatal spontaneously hypertensive rats

    PubMed Central

    Cates, Matthew J.; Steed, Peter W.; Abdala, Ana P. L.; Langton, Philip D.

    2011-01-01

    There is a strong correlation between increased vertebral artery resistance and arterial blood pressure in humans. The reasons for this increased resistance at high systemic pressure remain unknown, but may include raised sympathetic activity. With the recent finding that prehypertensive spontaneously hypertensive (PHSH) rats, which have raised sympathetic nerve activity, but a blood pressure comparable to normotensive rat strains, we hypothesized that its vertebrobasilar vascular resistance would already be raised and, as a consequence, would exhibit a more responsive Cushing response (e.g., brain ischemia evoked sympathoexcitation and a pressor response). We report that PHSH rats exhibited a remodeling of the basilar artery (i.e., increased wall thickness and lower lumen-to-wall thickness ratio) that occurred before the onset of hypertension. In a novel in vitro vascularly isolated, arterially perfused brain stem preparation of PHSH rats of 4–5 wk of age, brain stem vascular resistance was raised by ∼35% relative to age- and sex-matched normotensive rats (P < 0.05). In the in situ arterial perfused working heart-brain stem preparation, occlusion of both vertebral arteries in the PHSH rat resulted in a significantly greater increase in sympathetic activity (57 vs. 20%, PHSH vs. control; P < 0.01) that triggered a greater increase in arterial perfusion pressure (8 vs. 3 mmHg, PHSH vs. control; P < 0.01) compared with normotensive rats. These data indicate raised vertebrobasilar artery resistance before the onset of hypertension in the PHSH rat. With the raised responsiveness of the Cushing response in the PHSH rat, we discuss the possibility of brain stem perfusion as a central nervous system determinant of the set point of vasomotor sympathetic tone in the hypertensive condition. PMID:21493719

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

    PubMed

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

    2017-04-01

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

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

    PubMed

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

    2016-01-01

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

  8. Prostanoid therapies in the management of pulmonary arterial hypertension

    PubMed Central

    LeVarge, Barbara L

    2015-01-01

    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 with PAH; this pathway has thus become a therapeutic target. Epoprostenol, the synthetic equivalent of prostacyclin, was first utilized as short-term or bridging therapy in the 1980s. Further refinement of its long-term use via continuous intravenous infusion followed. A randomized controlled trial by Barst et al in 1996 demonstrated functional, hemodynamic, and mortality benefits of epoprostenol use. This work was a groundbreaking achievement in the management of PAH and initiated a wave of research that markedly altered the dismal prognosis previously associated with PAH. Analogs of prostacyclin, including iloprost and treprostinil, exhibit increased stability and allow for an extended array of parenteral and non-parenteral (inhaled and oral) therapeutic options. This review further examines the pharmacology and clinical use of epoprostenol and its analogs in PAH. PMID:25848300

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

    PubMed

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

    2012-06-01

    This study aimed to investigate the safety, tolerability, and effects of tadalafil on children with pulmonary arterial hypertension (PAH) after transition from sildenafil or after tadalafil received as initial therapy. A total of 33 pediatric patients with PAH were retrospectively evaluated. Of the 33 patients, 29 were switched from sildenafil to tadalafil. The main reason for the change from sildenafil was once-daily dosing. The average dose of sildenafil was 3.4 ± 1.1 mg/kg/day, and that of tadalafil was 1.0 ± 0.4 mg/kg/day. For 14 of the 29 patients undergoing repeat catheterization, statistically significant improvements were observed after transition from sildenafil to tadalafil in terms of mean pulmonary arterial pressure (53.2 ± 18.3 vs. 47.4 ± 13.7 mmHg; p < 0.05) and pulmonary vascular resistance index (12.2 ± 7.0 vs 10.6 ± 7.2 Units/m(2); p < 0.05). Clinical improvement was noted for four patients treated with tadalafil as initial therapy. The side effect profiles were similar for the patients who had transitioned from sildenafil to tadalafil including headache, nausea, myalgia, nasal congestion, flushing, and allergic reaction. Two patients discontinued tadalafil due to migraine or allergic reaction. One patient receiving sildenafil had no breakthrough syncope after transition to tadalafil. Tadalafil can be safely used for pediatric patients with PAH and may prevent disease progression.

  10. Patients with resistant hypertension have more peripheral arterial disease than other uncontrolled hypertensives.

    PubMed

    Korhonen, P E; Kautiainen, H; Kantola, I

    2015-01-01

    The aim of this study was to investigate whether resistant hypertension differs from uncontrolled and controlled hypertension in terms of target organ damage. Hypertensive subjects with antihypertensive medication (n=385) were identified in a population survey conducted in southwestern Finland. None of the study subjects had previously diagnosed cardiovascular or renal disease or diabetes. Ankle-brachial index, estimated glomerular filtration rate, electrocardiogram-determined left ventricular hypertrophy and cardiometabolic risk factors were assessed. The prevalence of peripheral arterial disease among subjects with resistant, uncontrolled and controlled hypertension was 6/37 (16%), 22/275 (8%) and 0/73 (0%), respectively (P=0.006). There were no differences in the prevalence of renal insufficiency, left ventricular hypertrophy or metabolic parameters between the groups. Resistant hypertension affects vasculature more than uncontrolled hypertension, and thus it can be regarded as a marker of more severe disease.

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

    PubMed

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

    2017-03-01

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

  12. Nodular transformation of the liver associated with portal and pulmonary arterial hypertension.

    PubMed

    Portmann, B; Stewart, S; Higenbottam, T W; Clayton, P T; Lloyd, J K; Williams, R

    1993-02-01

    A case of multiple focal nodular hyperplasia (FNH) of the liver associated with noncirrhotic portal hypertension and later complicated by pulmonary arterial hypertension leading to death from right heart failure is reported. In retrospect, the portal hypertension diagnosed in early life was most likely due to a congenital hypoplasia of portal vein branches and multiple FNH, a hyperplastic response of the liver parenchyma in association with anomalies of hepatic arterial branches as found within the lesions. This case may represent a form of multiple FNH syndrome restricted to the liver, because neither extrahepatic vascular malformation nor brain tumor was identified at autopsy. The FNH lesions had considerably expanded over the years, and the severe sinusoidal congestion due to chronic right-sided heart failure with subsequent prolonged parenchymal exposure to blood-borne hepatotrophic factors is a likely explanation for both the massive enlargement of FNH lesions and the nodular regenerative hyperplasia observed in the intervening parenchyma.

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

    PubMed

    Agabiti-Rosei, Enrico; Porteri, Enzo; Rizzoni, Damiano

    2009-01-01

    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 beta-blockers on indices of arterial stiffness was observed in several studies. It is conceivable that newer beta-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 beta-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 implications for the use of this agent in the treatment of hypertension and cardiovascular diseases.

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

    PubMed Central

    Agabiti-Rosei, Enrico; Porteri, Enzo; Rizzoni, Damiano

    2009-01-01

    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 implications for the use of this agent in the treatment of hypertension and cardiovascular diseases. PMID:19475771

  15. [Clinical utility of inhaled iloprost in pulmonary arterial hypertension].

    PubMed

    Santos-Martínez, Luis Efren; Moreno-Ruiz, Luis Antonio; Jiménez-Santos, Moisés; Olmos-Temois, Sergio Gabriel; Bojorquez-Guerrero, Luis Armando; Baranda-Tovar, Francisco Martín

    2014-01-01

    Inhaled iloprost is a drug from the group of prostacyclins used in the treatment of pulmonary arterial hypertension. Its efficacy and safety have allowed its use as monotherapy and combination therapy. This review describes the product characteristics, amenable to treatment groups, and updated clinical evidence of drug use.

  16. [Pulmonary arterial hypertension associated to human immunodeficiency virus].

    PubMed

    Sandoval-Gutiérrez, José Luis; Santos-Martínez, Luis Efren; Rodríguez-Silverio, Juan; Baranda-Tovar, Francisco Martín; Rivera-Rosales, Rosa María; Flores-Murrieta, Francisco Javier

    2015-01-01

    From the advent of the highly effective antiretroviral treatment, the life expectancy of patients with human immunodeficiency virus has increased significantly. At present, the causes of death are non-infectious complications. Between them, the pulmonary arterial hypertension has a special importance. It is important early detection to establish the therapeutic, with the objective of preventing a fatal outcome to future.

  17. Pulmonary Arterial Hypertension-A Deadly Complication of Systemic Sclerosis

    PubMed Central

    Pankey, Edward A; Epps, Matthew; Nossaman, Bobby D; Hyman, Albert L; Kadowitz, Philip J

    2011-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease with limited therapeutic options. Moreover, when PAH occurs in patients diagnosed with systemic sclerosis, worse outcomes are observed. The purpose of this review is to discuss the etiologies of PAH found in the systemic sclerosis patient, limitations of current medical therapies, and, finally, potential therapies for patients with this combination. PMID:23626904

  18. Peripheral pulmonary artery stenosis as a cause of pulmonary hypertension in adults

    PubMed Central

    Ahmed, Mostafa; Hamed, Fadi; Prieto, Lourdes R.

    2015-01-01

    Abstract Peripheral pulmonary artery stenosis (PPAS) is an underrecognized condition in the adult population. PPAS can lead to pulmonary hypertension but is likely misdiagnosed as either idiopathic pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. We retrospectively identified adult patients with PPAS either in its isolated form or related to other congenital defects from January 1998 to September 2012. We reviewed the patients’ clinical data by using our hospital electronic medical records and/or their paper charts. We identified 6 adult patients with PPAS with an age range of 16–56 years (1 woman and the rest men). Presenting signs and symptoms were thoracic murmurs, progressive dyspnea, and syncope. Three patients had Williams-Beuren syndrome. Pulmonary angiography showed that PPAS was predominantly located in main branches or lobar pulmonary arteries in 5 patients, while in 1 patient the arterial narrowing was at the level of the segmental pulmonary arteries. Right heart catheterization showed a mean pulmonary artery pressure (PAP) ranging from 35 to 60 mmHg. Balloon dilation was performed in all patients, predominantly in the lobar arteries, and it caused a decrease in mean PAP that ranged from 16% to 46% in 5 patients. In 1 patient the mean PAP did not decrease. All but 1 patient had follow-up echocardiograms at 1 year that showed stable echocardiographic findings. Pulmonary hypertension due to PPAS continues to presents a diagnostic challenge. Therefore, a high index of suspicion during the initial evaluation of pulmonary hypertension is essential for its prompt diagnosis and adequate treatment. PMID:25992283

  19. Relationship of effective arterial elastance to demographic and arterial characteristics in normotensive and hypertensive adults.

    PubMed

    Saba, P S; Roman, M J; Ganau, A; Pini, R; Jones, E C; Pickering, T G; Devereux, R B

    1995-09-01

    To evaluate demographic and vascular correlates of the effective arterial elastance noninvasively in normotensive and hypertensive adults. In 202 subjects carotid ultrasonography and external arterial tonometry were simultaneously performed; carotid cross-sectional area, absolute and relative wall thicknesses, Peterson's and Young's elastic moduli and beta', a pressure-dependent index of arterial stiffness, were calculated. The impact of reflected waves on central pressure waveforms was evaluated by the 'augmentation index' (the relative increment in systolic pressure caused by the late-systolic peak). Left ventricular mass and relative wall thickness were assessed echocardiographically. The effective arterial elastance was estimated by dividing the pressure at the dicrotic notch by the Doppler-determined stroke index. The effective arterial elastance was higher in women among normotensives but similar between sexes among hypertensive subjects. It was correlated to age, mean blood pressure, body mass index and measures of arterial function, including Peterson's and Young's elastic moduli and beta', and to the augmentation index. It was also related to absolute and relative carotid wall thicknesses, lumen diameter and indexed cross-sectional area. Age, beta' and carotid cross-sectional area independently predicted effective arterial elastance in multiple regression analysis. Effective arterial elastance is related to demographic and arterial structural and functional characteristics. Increases in effective arterial elastance resulting from altered arterial structure and function may play a role in inducing left ventricular adaptative modifications.

  20. [Arterial mean pressure and pulse pressure in young hypertensive patients].

    PubMed

    Carmona Puerta, Raimundo; Acosta de Armas, Francisco; Pérez de Armas, Alina; Morales Salinas, Alberto; González Paz, Héctor; Guirado Blanco, Otmara

    2006-09-02

    Evidence shows that pulse pressure (PP) is very useful when assessing the hypertensive patient and this has led to a lower use of mean arterial pressure (MAP). We intended to demonstrate that MAP should be better than PP in young hypertensive patients. Cross-sectional study in 70 white males with ages among 16-40 years, distributed in two groups of 35 individuals labelled as control group or hypertensive patients, who were assessed by echocardiography. PP was similar (36.37 +/- 7.90 mmHg vs. 36.67 +/- 9.41 mmHg, p = 0.8851) in both control and hypertensive groups, as well as the arterial compliance (2.22 +/- 0.62 ml/mmHg vs. 2.41 +/- 0.77 ml/mmHg, p = .2555) and the aortic stiffness index (0.88 +/- 0.23 vs. 0.91 +/- 0.33, P = .6591). MAP (94.85 +/- 8.68 mmHg vs. 115.11 +/- 10.01 mmHg, P < .001) and total peripheral resistance index (TPRI) [2681.42 +/- 602.31 dinas.s.cm-5/m2 vs. 3120.68 +/- 741.74 dinas.s.cm-5/m2, p = .0066] were higher in hypertensive patients. In our cross-sectional assessment in young hypertensive patients, MAP and its determiner (TPRI) were modified, with no important changes in the PP or its determiners.

  1. PREVALENCE OF DIABETES MELLITUS AMONG PATIENTS WITH ESSENTIAL ARTERIAL HYPERTENSION.

    PubMed

    Chahoud, Jad; Mrad, Jad; Semaan, Adele; Asmar, Roland

    2015-01-01

    This study evaluates the prevalence of diabetes mellitus (DM) among patients with arterial hypertension, and indirectly, the crucial impact of adopting screening for diabetes as a standard procedure for all patients diagnosed with arterial hypertension. This cross-sectional study was performed on a sample of hypertensive patients recruited from three different university hospitals in Lebanon. Blood pressure and glycemic blood measurements were determined in all subjects. In addition, a complete clinical history and physical exam were performed. Data was entered and analyzed using SPSS 19.0. Frequencies for the different variables were calculated, and the chi-square and independent sample t-tests were conducted. This study included 294 patients. Prevalence of diabetes was 27%, and 23% of diabetic patients were newly diagnosed. More than half of the subjects suffering from DM had uncontrolled blood pressure, contrasted with only one third of the non-diabetic subjects with uncontrolled hypertension. The prevalence of DM in patients with essential hypertension was more than double that of the general population. Therefore, major recommendations would be to adopt strictly the diabetes screening requirements and aggressive management among hypertensive patients to minimize both the health and cost burdens associated with undetected DM.

  2. [Arterial hypertension in elderly patients - from pathophysiology to rational treatment].

    PubMed

    Kucharska, Ewa

    2013-01-01

    According to the WHO, arterial hypertension is a major cause of death in adult populations all over the world, regardless of the socio-economic level of a specific population. In Poland, the presence of hypertension is estimated to be about 1/3 in the population of adult Poles. Although hypertension may occur in people of all ages, as the population is ageing, a large group of patients are those over 65. In this age group, the dominant form of arterial hypertension is the isolated systolic hypertension (ISH), in which increased systolic blood pressure is disclosed (higher than or equal to 140 mm Hg), with diastolic blood pressure values remaining within the normal range (<90 mm Hg). Even 15 years ago, the therapeutic approach to ISH in the elderly was a subject of a broad debate. Until the results of main clinical trials and meta-analyzes summarising these results were announced, it was not certain whether active treatment of these patients was beneficial. Moreover, the drug selection issue was hotly debated. The last major problem was the question concerning benefits resulting from the treatment of isolated systolic hypertension in patients aged 80 years and older.

  3. Risk factors of arterial hypertension after renal transplantation.

    PubMed

    Béji, S; Abderrahim, E; Kaaroud, H; Jebali, H; Ben Abdallah, T; El Younsi, F; Ben Moussa, F; Ben Hamida, F; Sfaxi, A; Blah, M; Chebil, M; Ayed, M; Bardi, R; Gorgi, Y; Kheder, A

    2007-10-01

    Arterial hypertension often present after kidney transplantation is of multifactorial origin. The aim of this study was to determine the role of donor and recipient factors in the development of hypertension after renal transplantation. We retrospectively analyzed the data of 280 patients transplanted between 1985 and 2005, who still had functioning grafts at 1 year after transplantation. We recorded donor and recipient parameters. One hundred eighty-seven patients (66.8%) were hypertensive. Upon multivariate analysis of recipient factors, pretransplant hypertension (odds ratio) [OR]: 8.5, 95% confidence interval [CI]: 4.5 to 16.1); serum creatinine level > 130 micromol/L at 6 months (OR: 2.5, 95% CI: 1.3 to 4,7), male gender (OR: 2.02, 95% CI: 1.2 to 3.4), and chronic rejection (OR: 2.4, 95% CI: 1.2 to 4.7) were independent predisposing factors. Among donor factors, age was significantly associated with arterial hypertension upon univariate analysis. In conclusion, recipient factors, especially pretransplant hypertension, contribute to the disorder in renal transplant patients.

  4. [Lung function testing in patients with pulmonary arterial hypertension].

    PubMed

    Escribano, P Martín; Sánchez, M A Gómez; de Atauri, M J Díaz; Frade, J Palomera; García, I Martín

    2005-07-01

    The main objective was to describe the results of lung function testing in a series of 120 patients with pulmonary arterial hypertension, and the secondary objective was to compare these findings with hemodynamic variables. This was a descriptive study of lung function in 120 patients with stable pulmonary arterial hypertension (Evian/Venice groups 1 and 4) studied until January 2002 in the Pulmonary Hypertension and Lung Transplant Working Group attached to the Cardiology Department of the Hospital Universtario 12 de Octubre in Madrid, Spain. Data were collected retrospectively for the first 47 patients (1981 to 1995) and prospectively thereafter for the remaining 73 patients. The diagnosis was idiopathic arterial hypertension or hypertension associated with collagenosis, chronic pulmonary embolism, cardiac shunt, or toxic oil syndrome (30 cases). In the group as a whole, forced vital capacity, forced expiratory volume in 1 second, and total lung capacity were normal; mean (SD) values revealed low carbon dioxide diffusing capacity (67.6% [23.2%]), and moderate hypoxemia (65.8 [15.4] mm Hg). No significant associations were observed between lung function and hemodynamic parameters. Mean age in the toxic oil syndrome group was lower (33.7 [11.4] years), and these patients had higher mean scores on the New York Heart Association scale (3.3 [0.5]) and for pulmonary vascular resistance (20.3 [8.1] kPa.L(-1).s). Lung function was studied in a series of 120 patients with pulmonary arterial hypertension (Evian/ Venice groups 1 and 4), 30 of whom had toxic oil syndrome. No significant associations were found between lung function and hemodynamic parameters.

  5. Alterations in structure and mechanics of resistance arteries from ouabain-induced hypertensive rats.

    PubMed

    Briones, Ana M; Xavier, Fabiano E; Arribas, Silvia M; González, M Carmen; Rossoni, Luciana V; Alonso, María J; Salaices, Mercedes

    2006-07-01

    We have previously described that chronic administration of ouabain induces hypertension and functional alterations in mesenteric resistance arteries. The aim of this study was to analyze whether ouabain treatment also alters the structural and mechanical properties of mesenteric resistance arteries. Wistar rats were treated for 5 wk with ouabain (8.0 microg/day sc). The vascular structure and mechanics of the third-order branches of the mesenteric artery were assessed with pressure myography and confocal microscopy. Total collagen content was determined by picrosirius red staining, collagen I/III was analyzed by Western blot, and elastin was studied by confocal microscopy. Vascular reactivity was analyzed by wire myography. Internal and external diameters and cross-sectional area were diminished, whereas the wall-to-lumen ratio was increased in arteries from ouabain-treated rats compared with controls. In addition, arteries from ouabain-treated rats were stiffer. Ouabain treatment decreased smooth muscle cell number and increased total and I/III collagens in the vascular wall. However, this treatment did not modify adventitia and media thickness, nuclei morphology, elastin structure, and vascular reactivity to norepinephrine and acetylcholine. The present work shows hypotrophic inward remodeling of mesenteric resistance arteries from ouabain-treated rats that seems to be the consequence of a combination of decreased cell number and impaired distension of the artery, possibly due to a higher stiffness associated with collagen deposition. The narrowing of resistance arteries could play a role in the pathogenesis of hypertension in this model.

  6. Arterial hypertension perpetuates alveolar bone loss.

    PubMed

    de Medeiros Vanderlei, Janine Montenegro Toscano Moura; Messora, Michel Reis; Fernandes, Patrícia Garani; Novaes, Arthur B; Palioto, Daniela Bazan; de Moraes Grisi, Marcio Fernando; Scombatti de Souza, Sergio Luis; Gerlach, Raquel Fernanda; Antoniali, Cristina; Taba, Mario

    2013-01-01

    Few studies have focused on the impact of hypertension on the progression of periodontitis (PD). The purpose of this study was to evaluate whether hypertension affects PD by enhancing bone loss even after the stimulus for PD induction is removed. Ligature-induced PD was created on the first mandibular molars of spontaneously hypertensive rats (SHR) and normotensive rats (Wistar Kyoto-WKY). The animals were assigned to non-ligated controls (C) and PD groups: WKY-C, WKY-PD, SHR-C, and SHR-PD. After 10 days, five animals of each group were killed and the ligatures of the other animals were removed. On the 21st day (11 days without PD induced), the remaining animals were killed. The jaws were defleshed and the amount of bone loss was measured. After 10 days, the PD groups showed more bone loss than its controls (P < .05); SHR-PD = 0.72 ± 0.05 mm, SHR-C = 0.39 ± 0.04 mm, WKY-PD = 0.75 ± 0.04 mm, and WKY-C = 0.56 ± 0.04 mm. The cumulative bone loss on day 21 (0.94 ± 0.13 mm) was significantly worse than on day 10 only in SHR-PD group (P < .05). The final bone loss differences between PD and C groups accounted for 102% (SHR) and 26% (WKY) increase in comparison with the initial control levels. Hypertension is associated with progressive alveolar bone loss even when the stimulus for PD induction is removed and it may be speculated that host condition perpetuates alveolar bone loss.

  7. Coronary Artery Atherosclerosis in Hypertensive Patients: The Role of Fibrinogen Genetic Variability.

    PubMed

    Papageorgiou, Nikolaos; Briasoulis, Alexandros; Hatzis, Georgios; Androulakis, Emmanuel; Kozanitou, Maria; Miliou, Antigoni; Charakida, Marietta; Zacharia, Effimia; Papaioannou, Spyridon; Paroutoglou, Ioannis; Siasos, Gerasimos; Pallantza, Zoi; Tousoulis, Dimitris

    2017-01-01

    We examined whether the rs180070 and rs2070011 polymorphisms of the fibrinogen gene could affect the risk of coronary artery disease in hypertensive patients by modifying the inflammatory process and coagulation. A total of 744 participants underwent coronary angiography due to symptoms of stable angina, while hypertension was present in 332 patients. The presence of the A allele (rs180070) was associated with significantly high levels of fibrinogen in hypertensive patients (P=.05). On multivariate analysis, A homozygosity (rs180070) (β = 0.257 ± 18.6; P<.001), but not hypertension status (β = 0.05 ± 11.9; P=.29) was an independent predictor of fibrinogen levels. In hypertensive patients, higher fibrinogen levels>443mg/dL (odds ratio = 3.50; 95% confidence interval, 1.14-10.90; P=.029), but not A homozygosity (odds ratio = 3.00; 95% confidence interval, 0.78-11.90; P = .110) were independent predictors of the presence of coronary artery disease. Moreover, interleukin-6 levels were higher in A homozygotes for the rs180070 polymorphism compared with all other genotypes (P=.046). Indeed, this genotype was the only adjusted independent predictor of interleukin-6 levels (β = 0.151 ± 0.642; P=.032). It was also associated with higher D-dimer levels in hypertension compared with G allele carriers (P=.048). The presence of A homozygosity (rs180070) is associated with increased levels of inflammatory mediators and a higher incidence of angiographic coronary artery disease. Importantly, fibrinogen is an independent predictor of the angiographic presence of coronary artery disease in hypertensive patients. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  8. Lineage Analysis in Pulmonary Arterial Hypertension

    DTIC Science & Technology

    2013-06-01

    SMA with some globular domains, predominantly colocalizing with GFP endothelial lineage-marked cells in the neointima (Figure 4F). Figure 4. VE...whether the neointima arises from a small population of apoptosis- resistant pulmonary artery endothelial cells that proliferate after injury to produce

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

    PubMed

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

    2012-12-01

    We sought to explore the pulmonary haemodynamic changes in rheumatic mitral stenosis patients with secondary pulmonary hypertension. The pulmonary artery resistance and compliance of 35 patients with rheumatic mitral stenosis and 12 controls without cardiopulmonary vascular disease were evaluated by using an improved method, which is based on making calculations with parameters obtained from right heart catheterisation. The results are as follows: (1) pulmonary artery compliance in patients with secondary pulmonary hypertension was significantly lower than that of the control group (P<0.01); (2) linear correlation analyses showed that preoperative mean pulmonary artery pressure (mPAP) closely correlated with zero-pressure compliance in the mitral stenosis group (r=-0.745, P<0.05); (3) PAP and pulmonary vascular resistance decreased significantly in both groups with mitral stenosis after infusing 0.5 μg kg(-1) min(-1) of sodium nitroprusside (P<0.01). The pulmonary zero pressure compliance and mean pressure compliance increased significantly in the group with mild pulmonary hypertension; whereas in the severe group, the mean compliance changed with significance as the mPAP decreased (1.51 ± 0.59 vs 1.81 ± 0.77 ml/mmHg), however no significant change occurred in the pulmonary zero pressure compliance (2.35 ± 1.24 ml/mmHg vs. 2.24 ± 1.53 ml/mmHg, P>0.05) The walls of pulmonary artery vessels in patients with pulmonary hypertension secondary to rheumatic mitral stenosis appeared to be remodelled by varying degrees as indicated by their haemodynamic properties. Structural remodelling may be a factor affecting preoperative pulmonary artery pressure. Mitral stenosis patients with severe pulmonary hypertension have significantly lower responses to sodium nitroprusside possibly due to aggradation and deposition of collagen in the artery walls, decreasing constriction and dilation, or atrophy of smooth muscle cells.

  10. Differential susceptibility to hypertension is due to selection during the out-of-Africa expansion.

    PubMed

    Young, J Hunter; Chang, Yen-Pei C; Kim, James Dae-Ok; Chretien, Jean-Paul; Klag, Michael J; Levine, Michael A; Ruff, Christopher B; Wang, Nae-Yuh; Chakravarti, Aravinda

    2005-12-01

    Hypertension is a leading cause of stroke, heart disease, and kidney failure. The genetic basis of blood pressure variation is largely unknown but is likely to involve genes that influence renal salt handling and arterial vessel tone. Here we argue that susceptibility to hypertension is ancestral and that differential susceptibility to hypertension is due to differential exposure to selection pressures during the out-of-Africa expansion. The most important selection pressure was climate, which produced a latitudinal cline in heat adaptation and, therefore, hypertension susceptibility. Consistent with this hypothesis, we show that ecological variables, such as latitude, temperature, and rainfall, explain worldwide variation in heat adaptation as defined by seven functional alleles in five genes involved in blood pressure regulation. The latitudinal cline in heat adaptation is consistent worldwide and is largely unmatched by latitudinal clines in short tandem repeat markers, control single nucleotide polymorphisms, or non-functional single nucleotide polymorphisms within the five genes. In addition, we show that latitude and one of these alleles, GNB3 (G protein beta3 subunit) 825T, account for a major portion of worldwide variation in blood pressure. These results suggest that the current epidemic of hypertension is due to exposures of the modern period interacting with ancestral susceptibility. Modern populations differ in susceptibility to these new exposures, however, such that those from hot environments are more susceptible to hypertension than populations from cold environments. This differential susceptibility is likely due to our history of adaptation to climate.

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

    PubMed

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

    2011-01-01

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

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

    PubMed

    Papathanasiou, Athanasios; Nakos, George

    2015-11-04

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

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

    PubMed Central

    Patrono, Damiano; Benvenga, Rosa; Moro, Francesco; Rossato, Denis; Romagnoli, Renato; Salizzoni, Mauro

    2014-01-01

    INTRODUCTION Left-sided portal hypertension is a rare clinical condition most often associated with a pancreatic disease. In case of hemorrhage from gastric fundus varices, splenectomy is indicated. Commonly, the operation is carried out by laparotomy, as portal hypertension is considered a relative contraindication to laparoscopic splenectomy (LS). Although some studies have reported the feasibility of the laparoscopic approach in the setting of cirrhosis-related portal hypertension, experience concerning LS in left-sided portal hypertension is lacking. PRESENTATION OF CASE A 39-year-old man was admitted to the Emergency Department for haemorrhagic shock due to acute hemorrhage from gastric fundus varices. Diagnostic work up revealed a chronic pancreatitis-related splenic vein thrombosis causing left-sided portal hypertension with gastric fundus varices and splenic cavernoma. Following splenic artery embolization (SAE), the case was successfully managed by LS. DISCUSSION The advantages of laparoscopic over open splenectomy include lower complication rate, quicker recovery and shorter hospital stay. Splenic artery embolization prior to LS has been used to reduce intraoperative blood losses and conversion rate, especially in complex cases of splenomegaly or cirrhosis-related portal hypertension. We report a case of complicated left-sided portal hypertension managed by LS following SAE. In spite of the presence of large varices at the splenic hilum, the operation was performed by laparoscopy without any major intraoperative complication, thanks to the reduced venous pressure achieved by SAE. CONCLUSION Splenic artery embolization may be a valuable adjunct in case of left-sided portal hypertension requiring splenectomy, allowing a safe dissection of the splenic vessels even by laparoscopy. PMID:25194596

  14. Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus: Prevalence and Predictors.

    PubMed

    Pérez-Peñate, Gregorio Miguel; Rúa-Figueroa, Iñigo; Juliá-Serdá, Gabriel; León-Marrero, Fernándo; García-Quintana, Antonio; Ortega-Trujillo, José Ramón; Erausquin-Arruabarrena, Celia; Rodríguez-Lozano, Carlos; Cabrera-Navarro, Pedro; Ojeda-Betancor, Nazario; Gómez-Sánchez, Miguel Ángel

    2016-02-01

    Pulmonary arterial hypertension (PAH) prevalence has been reported to be between 0.5% and 17% in systemic lupus erythematosus (SLE). This study assessed PAH prevalence and predictors in an SLE cohort. The Borg dyspnea scale, DLCO, N-terminal pro-brain natriuretic peptide (NT-proBNP), and Doppler echocardiographic (DE) were performed. An echocardiographic Doppler exercise test was conducted in selected patients. When DE systolic pulmonary arterial pressure was ≥ 45 mmHg or increased during exercise > 20 mmHg, a right heart catheterization was performed. Hemodynamic during exercise was measured if rest mean pulmonary arterial pressure was < 25 mmHg. Of the 203 patients with SLE, 152 were included. The mean age was 44.9 ± 12.3 years, and 94% were women. Three patients had known PAH. The algorithm diagnosed 1 patient with chronic thromboembolic pulmonary hypertension and 5 with exercise-induced pulmonary artery pressure increase (4 with occult left diastolic dysfunction). These patients had significantly more dyspnea, higher NT-proBNP, and lower DLCO. These data confirm the low prevalence of PAH in SLE. In our cohort, occult left ventricular diastolic dysfunction was a frequent diagnosis of unexplained dyspnea. Dyspnea, DLCO, and NT-proBNP could be predictors of pulmonary hypertension in patients with SLE.

  15. Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

    SciTech Connect

    Suzuki, Chihiro; Takahashi, Masafumi . E-mail: masafumi@sch.md.shinshu-u.ac.jp; Morimoto, Hajime; Izawa, Atsushi; Ise, Hirohiko; Hongo, Minoru; Hoshikawa, Yasushi; Ito, Takayuki; Miyashita, Hiroshi; Kobayashi, Eiji; Shimada, Kazuyuki; Ikeda, Uichi

    2006-10-20

    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.

  16. [Female gender and pulmonary arterial hypertension: a complex relationship].

    PubMed

    Manes, Alessandra; Palazzini, Massimiliano; Dardi, Fabio; D'Adamo, Antonio; Rinaldi, Andrea; Galiè, Nazzareno

    2012-06-01

    Pulmonary arterial hypertension (PAH) is a severe clinical condition defined as mean pulmonary artery pressure ≥25 mmHg and normal pulmonary capillary wedge pressure (≤15 mmHg). In PAH the increase in pulmonary pressure is due to an intrinsic disease of the small pulmonary arteries (resistance vessels) characterized by vascular proliferation and remodeling. The increase in pulmonary vascular resistance with subsequent elevation of the right ventricular afterload leads to right ventricular failure after variable periods of time. Although targeted disease therapies have been developed over the last decade that resulted in improved quality of life and outcome for PAH patients, the prognosis is still severe and there remains no cure for this disease. From a clinical standpoint, PAH includes a group of heterogeneous pathological conditions: in idiopathic, heritable and drug- and toxin-induced PAH, since there are no predisposing clinical conditions, the structural changes in pulmonary circulation are "isolated"; on the other hand, PAH may be associated with some predisposing diseases such as connective tissue disease, HIV infection, portal hypertension, congenital heart disease, schistosomiasis, and chronic hemolytic anemia. PAH can affect individuals of all age groups, and mean age at diagnosis is around 50 years. Epidemiological data show a great preponderance of females in PAH; the high prevalence of females is particularly evident in the so-called "isolated" PAH forms, whereas in PAH associated with other diseases the female:male ratio is strongly influenced by the epidemiological features of the specific predisposing condition. The reason for the higher female prevalence in PAH has never been clarified: some hypotheses involve the role of sexual hormones (estrogens), autoimmunity, or an X-linked locus in disease predisposition. Female gender is not associated with a different clinical presentation. However, the age of onset tends to be earlier in females than

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

    PubMed

    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.

  18. [The correction of arterial hypertension by oxygen deprivation].

    PubMed

    Berezovs'kyï, V Ia; Levashov, M I

    2000-01-01

    Curative effect of oxygen deprivation has been examined in 147 patients with initial studies of hypertonic disease. It was used the intermittent model of the oxygen deprivation. The oxygen partial pressure in the breathing gaseous mixtures was 90-110 mm Hg. The positive effect was achieved in 79% of patients. Arterial pressure decreasing at the expense of different hemodynamic mechanisms depending on the type of blood circulation. It is proposing to use the oxygen deprivation as the correction method for the initial studies of the arterial hypertension.

  19. Clinical and molecular genetic features of hereditary pulmonary arterial hypertension.

    PubMed

    Brenner, Laura; Chung, Wendy K

    2011-10-01

    Pulmonary arterial hypertension (PAH) is a rare disorder that may be hereditary (HPAH), idiopathic (IPAH), or associated with either drug-toxin exposures or other medical conditions. Familial cases have long been recognised and are usually due to mutations in the bone morphogenetic protein receptor type 2 gene (BMPR2), or, much less commonly, two other members of the transforming growth factor-β superfamily, activin-like kinase-type 1 (ALK1), and endoglin (ENG), which are associated with hereditary hemorrhagic telangiectasia. In addition, approximately 20% of patients with IPAH carry mutations in BMPR2. Clinical testing for BMPR2 mutations is available and may be offered to HPAH and IPAH patients but should be preceded by genetic counselling, since lifetime penetrance is only 10% to 20%, and there are currently no known effective preventative measures. Identification of a familial mutation can be valuable in reproductive planning and identifying family members who are not mutation carriers and thus will not require lifelong surveillance. With advances in genomic technology and with international collaborative efforts, genome-wide association studies will be conducted to identify additional genes for HPAH, genetic modifiers for BMPR2 penetrance, and genetic susceptibility to IPAH. In addition, collaborative studies of BMPR2 mutation carriers should enable identification of environmental modifiers, biomarkers for disease development and progression, and surrogate markers for efficacy end points in clinical drug development, thereby providing an invaluable resource for trials of PAH prevention.

  20. Pediatric Pulmonary Arterial Hypertension and Hyperthyroidism: A Potentially Fatal Combination

    PubMed Central

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

    2012-01-01

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

  1. Inflammatory mechanisms in HIV-associated pulmonary arterial hypertension.

    PubMed

    Tcherakian, Colas; Couderc, Louis-Jean; Humbert, Marc; Godot, Véronique; Sitbon, Olivier; Devillier, Philippe

    2013-10-01

    Pulmonary arterial hypertension (PAH) is a severe complication of human immunodeficiency virus (HIV) infection and a leading major cause of death when present. HIV-PAH could be the consequence of multiple hits including the direct effects of HIV proteins, use of illicit drugs, and chronic inflammation. Indeed, HIV infection has long been identified as an immunosuppressive disease but, since the advent of highly active antiretroviral treatments (HAART), HIV infection is considered as an inflammatory disease in which vascular complications have become a major cause of morbidity and death. Conversely to immunosuppression, which correlates with blood CD4 + T cell level, inflammation in HIV infection is due to the lack of gut CD4 + T cell restoration. Such gut T cell depletion favors lipopolysaccharide translocation and, in turn, chronic systemic interleukin-6 overproduction. Conversely to blood CD4 + T cells, gut CD4 + T cells are only partially restored with HAART, usually slowly after several months or years, with a large heterogeneity from one patient to another. These characteristics may cause chronic inflammation, and we hypothesize that PAH may occur because of this inflammatory component despite HAART, even with apparently good response to therapy (i.e., blood CD4 + T cell normalization and undetectable HIV load). Inflammation theory in HIV-PAH (as in other forms of PAH) could open new treatment options.

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

    PubMed

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

    2017-03-08

    The study of early development of the arterial hypertension in association with emotional stress is of great importance for better understanding of etiolody and pathogenesis of the hypertensive disease. MRI technique was applied to evaluate the hemodynamic and brain metabolites changes in 1- and 3-Mo-old ISIAH rats (10 male rats) with stress-sensitive arterial hypertension and in control normotensive WAG rats (8 male rats). In the 3-Mo-old ISIAH rats, age-dependent increase in the blood pressure was associated with increased blood flow through the renal arteries and decreased blood flow in the lower part of abdominal aorta. The renal vascular resistance in the ISIAH rats decreased while aging, though, at both ages it remained higher than the renal vascular resistance in WAG rats. Integral metabolome portrait demonstrated that hypertension development in the ISIAH rats was associated with attenuation of excitatory and energetic activity in the prefrontal cortex, whereas in the WAG rats, the opposite age-dependent changes were observed. In contrast, in hypothalamus of 3-Mo-old ISIAH rats, an increase in energetic activity and prevalence of excitatory neurotransmitters over inhibitory was noticed. The blood flow through the main arteries showed positive correlation with glutamate and glutamine levels in hypothalamus, and negative one - with hypothalamic GABA level. The blood pressure values positively correlated with hypothalamic choline levels. Thus, the early development of the stress-sensitive hypertension in the ISIAH rats is accompanied by considerable changes both in brain metabolite ratios and in the parameters of blood flow through the main arteries. This article is protected by copyright. All rights reserved.

  3. [Advances in arterial hypertension and diabetes mellitus].

    PubMed

    Cordero, Alberto; Lekuona, Iñaki; Galve, Enrique; Mazón, Pilar

    2012-01-01

    In 2011, the importance of hypertension and diabetes mellitus as the two main risk factors responsible for the development of cardiovascular disease became clear, as did their significance as major public health issues. Compared with previous years, in which publication of the results of large clinical trials dominated scientific progress, in the last year, the focus has shifted to evidence that novel mechanisms associated with blood pressure, glucose metabolism and diabetes can influence cardiovascular disease. Of particular importance were clinical trials in the area of renal dysfunction, such as the SHARP and ROADMAP trials. Copyright © 2012 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  4. Comparison of Machine Learning Methods for the Arterial Hypertension Diagnostics

    PubMed Central

    Belo, David; Gamboa, Hugo

    2017-01-01

    The paper presents results of machine learning approach accuracy applied analysis of cardiac activity. The study evaluates the diagnostics possibilities of the arterial hypertension by means of the short-term heart rate variability signals. Two groups were studied: 30 relatively healthy volunteers and 40 patients suffering from the arterial hypertension of II-III degree. The following machine learning approaches were studied: linear and quadratic discriminant analysis, k-nearest neighbors, support vector machine with radial basis, decision trees, and naive Bayes classifier. Moreover, in the study, different methods of feature extraction are analyzed: statistical, spectral, wavelet, and multifractal. All in all, 53 features were investigated. Investigation results show that discriminant analysis achieves the highest classification accuracy. The suggested approach of noncorrelated feature set search achieved higher results than data set based on the principal components. PMID:28831239

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

    PubMed

    Perros, Frédéric; Humbert, Marc

    2005-02-12

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

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

    PubMed

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

    2005-01-01

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

  7. Macitentan for the treatment of pulmonary arterial hypertension

    PubMed Central

    Kholdani, Cyrus A; Fares, Wassim H; Trow, Terence K

    2014-01-01

    Macitentan is the most recently approved dual endothelin-receptor antagonist (ERA) for the treatment of symptomatic pulmonary arterial hypertension. Compared to other available ERAs, it demonstrates superior receptor-binding properties, with consequently improved tissue penetration, and a longer duration of action allowing for once-daily dosing. It has a favorable adverse-effect profile, with notably no demonstrable increase in the risk of hepatotoxicity or peripheral edema, but like other ERAs, it is potentially limited by significant anemia. Phase I data have demonstrated a favorable drug–drug interaction profile and no need for dose adjustment with hepatic and renal impairment. In the pivotal SERAPHIN study, treatment of symptomatic pulmonary arterial hypertension patients with macitentan led to statistically significant improvements in functional class, exercise tolerance, and hemodynamic parameters, in addition to a reduction in morbidity in an event-driven long-term trial. PMID:25473292

  8. [Pulmonary arterial hypertension in adult patients with congenital heart disease].

    PubMed

    Serino, G; Giacomazzi, F

    2010-01-01

    Pulmonary Hypertension (PH) is definited by a mean pulmonary artery pressure (PAPm) >25 mmHg at rest. The Dana Point 2008 Revised Classification System represents the most recent classification system update with respect of various etiologies of PH. About 10 % of adolescents or adults with uncorrected congenital heart disease (CHD) with left-to-right shunt and high pulmonary blood flow develop Pulmonary Arterial Hypertension (PAH) . Progressive vascular remodeling and increase in pulmonary vascular resistance (PVR) may ultimately lead to reversal of the shunt (pulmonary to systemic) causing cyanosis and determining the so-called Eisenmenger Syndrome (ES). Recent advances in the early diagnosis and medical targeted treatment of adult patients with CHD-PAH and ES can improve PAP, PVR and exercise tolerance, together with NYHA Class and survival, and may potentially reverse the vascular remodeling process in selected patients.

  9. Hypertension and impairment of endothelium-dependent relaxation of arteries from spontaneously hypertensive and L-NAME-treated Wistar rats.

    PubMed

    Sekiguchi, F; Miyake, Y; Hirakawa, A; Nakahira, T; Yamaoka, M; Shimamura, K; Yamamoto, K; Sunano, S

    2001-04-01

    Effects of chronic treatment of normotensive Wistar rats with N(omega)-nitro-L-arginine methyl ester (L-NAME) on blood pressure and on endothelium-dependent relaxation of the aorta, carotid and iliac arteries were studied. The endothelium-dependent relaxation was compared in arteries from normotensive Wistar Kyoto rats (WKY) and genetically hypertensive rats (stroke-prone spontaneously hypertensive rats, SHRSP). Chronic treatment of normotensive Wistar rats with L-NAME caused an elevation of blood pressure. The elevated blood pressure at 15 weeks of age was significantly higher in these animals than that of untreated Wistar rats, but lower than that of SHRSP. Endothelium-dependent relaxation of the arteries induced by acetylcholine (ACh) was almost abolished by chronic treatment with L-NAME. The remaining small relaxation in arteries from L-NAME-treated rats was completely inhibited by application of L-NAME (10(-4) M). In such preparations, higher concentrations of ACh induced a contraction, which was abolished by removal of the endothelium or by an application of indomethacin (10(-5) M). Endothelium-independent relaxation induced by sodium nitroprusside was similar between preparations from untreated and L-NAME-treated Wistar rats. Endothelium-dependent relaxation was significantly impaired in preparations from SHRSP, when compared with that in those from WKY. However, the impairment was less prominent in preparations from SHRSP than in those from L-NAME-treated rats. These results suggest that the impairment of endothelium-dependent relaxation in the arteries from L-NAME-treated rats is not due to the elevated blood pressure resulting from the chronic treatment, and that impairment of NO synthesis by the endothelium does not play a major role in the initiation of hypertension in SHRSP.

  10. Arterial hypertension and neurofibromatosis: renal artery stenosis and coarctation of abdominal aorta.

    PubMed Central

    Schürch, W.; Messerli, F. H.; Genest, J.; Lefebvre, R.; Roy, P.; Carter, P.; Rojo-Ortega, J. M.

    1975-01-01

    A 10-year-old girl had arterial hypertension, generalized neurofibromatosis, coarctation of the abdominal aorta and multiple stenoses at the origin of each renal artery. After resection of the stenotic areas and reimplantation of the renal arteries in the aorta, her arterial pressure decreased substantially. However, hypertension recurred and radiologic follow-up 4 1/2 years later showed distinct progression of the coarctation and renewed stenosis of all renal arteries at their origin. The stenotic areas showed eccentric intimal proliferation, frequently bulging into the lumen, with small nodular aggregates of smooth muscle cells and proliferation of fibrous tissue containing spindle-shaped nuclei in a palisading pattern. Hypertension associated with neurofibromatotic vascular disease has been described in 47 other patients in the literature. These patients have been young (mean age, 14 years) and predominantly male. In contrast to fibromuscular dysplasia, in which 95% of all stenoses are found in the distal two thirds of the renal arteries, in vascular neurofibromatosis more than 50% of the stenoses are found at the origin. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 PMID:810239

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

    PubMed Central

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

    2013-01-01

    Background Pulmonary arterial hypertension carries a high risk of mortality in pregnancy. Recent advances in treatment may improve disease course and allow for successful management of the pregnancy. Case Report We present the case of a 20-year-old gravida 1, para 0 with diagnosis of severe primary pulmonary hypertension. The patient was managed with epoprostenol (prostacyclin) infusion via an indwelling catheter, which was initiated at 23 weeks' gestation. The dose was adjusted to the patient's symptoms and a successful vaginal delivery was achieved at 36 weeks' gestation. Although maternal postpartum course was uncomplicated, unexplained neonatal demise occurred at 11 days of life. Conclusion Successful management of pulmonary hypertension in pregnancy can be accomplished with a multidisciplinary approach and intensive therapy. Long-term effects of epoprostenol on fetal or neonatal well-being are unknown. PMID:24147238

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

    PubMed

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

    2013-10-01

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

  13. [Consensus on Systemic Arterial Hypertension In México].

    PubMed

    Rosas-Peralta, Martín; Palomo-Piñón, Silvia; Borrayo-Sánchez, Gabriela; Madrid-Miller, Alejandra; Almeida-Gutiérrez, Eduardo; Galván-Oseguera, Héctor; Magaña-Serrano, José Antonio; Saturno-Chiu, Guillermo; Ramírez-Arias, Erick; Santos-Martínez, Efrén; Díaz-Díaz, Enrique; Salgado-Pastor, Selene Janette; Morales-Mora, Gerardo; Medina-Concebida, Luz Elena; Mejía-Rodríguez, Oliva; Pérez-Ruiz, Claudia Elsa; Chapa-Mejía, Luis Raúl; Álvarez-Aguilar, Cleto; Pérez-Rodríguez, Gilberto; Castro-Martínez, María Guadalupe; López-Bárcena, Joaquín; Paniagua-Sierra, José Ramón

    2016-01-01

    This Consenso Nacional de Hipertensión Arterial Sistémica (National Consensus on Systemic Arterial Hypertension) brings together experiences and joint work of 79 specialists who have been in contact with the patient affected by systemic arterial hypertension. All concepts here presented were outlined on the basis of the real world practice of Mexican hypertensive population. The consensus was developed under strict methodological guidelines. The Delphi technique was applied in two rounds for the development of an appropriate statistical analysis of the concepts exposed by all the specialists, who posed key questions, later developed by the panel of experts of the Hospital de Cardiología, and specialists from the Centro Médico Nacional. Several angles of this illness are shown: detection, diagnosis, pathophysiology, classification, treatment and prevention. The evidence analysis was carried out using PRISMA method. More than 600 articles were reviewed, leaving only the most representative in the references. This document concludes with practical and useful recommendations for the three levels of health care of our country.

  14. Regional differences in the prevalence of arterial hypertension in Croatia.

    PubMed

    Erceg, Marijan; Kern, Josipa; Babić-Erceg, Andrea; Ivicević-Uhernik, Ana; Vuletić, Silvije

    2009-04-01

    This paper analyzes the Croatian Adult Health Survey data, collected in 2003 with a total of 9,070 respondents aged 18+. Based on an average of two measurements, respondents with the mean systolic arterial pressure > or = 140 mmHg or mean diastolic pressure > or = 90 mmHg were classified as hypertensive. The data for men and women were analyzed separately, according to regions. Prevalence of hypertension in men was 40.5% (95% confidence interval CI 37.9-43.01; coefficient of variability CV = 3.2), women 34.9% (95% CI 33.2-36.7; CV 2.5). There were no significant differences in regional prevalence in men, except in the Northern and Eastern region. In women we did not detect any significant regional difference. Non-controlled arterial hypertension is an important public health problem in all monitored regions of Croatia. Raising awareness about the problem, early detection and encouraging the population to adhere to the therapy for elevated arterial pressure, in addition to a healthy life style, are important for successful control and harm reduction.

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

    PubMed

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

    2016-02-15

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

  16. Exercise hypertension in the perspective of systemic arterial hypertension. An overview.

    PubMed

    Landry, F; Jetté, M; Blümchen, G

    1987-04-01

    Systemic arterial hypertension is one of the most wide-spread diseases in the world. It is a chronic disease with a very long asymptomatic phase. At an estimated prevalence in the developed countries of 15 to 20%, it can be assumed that approximately 80% of men and 60% of women with hypertension are either unaware of their condition or are not treated adequately. These figures show that reliable diagnostic measures are needed to provide efficient detection of high blood pressure in a given population. In this regard, exercise testing has proven particularly well-suited. Using standardized ergometry, patients with latent, borderline or manifest hypertension can be identified. Exercise hypertension is defined on the basis of an abnormal blood pressure increase during physical exercise in persons with normal blood pressure at rest. Because of marked interindividual fluctuation in blood pressure, values measured at rest may be of only limited usefulness in the diagnosis of hypertension. In contrast, the blood pressure during dynamic exercise may be particularly informative with respect to probability of future development of manifest hypertension and treatment of high blood pressure. Long-term studies have shown that within five years up to one-third of patients with exercise hypertension develop manifest hypertension at rest. Based on the Canada Fitness Survey data indicating that about 2% of the population demonstrate exercise hypertension, it can be estimated that approximately 200,000 Canadians will develop manifest hypertension within five years. Similar statistics are also applicable for most of the developed countries of the world.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    PubMed

    Fraisse, A; Habib, G

    2004-08-01

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

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

    PubMed Central

    Arnold, Nadine D.; Chang, William; Watson, Oliver; Swift, Andrew J.; Condliffe, Robin; Elliot, Charlie A.; Kiely, David G.; Suvarna, S. Kim; Gunn, Julian; Lawrie, Allan

    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 demonstrate denervation of the pulmonary artery at a histological level. Methods and Results— Histological evaluation identified a circumferential distribution of nerves around the proximal pulmonary arteries. Nerves were smaller in diameter, greater in number, and located in closer proximity to the luminal aspect of the pulmonary arterial wall beyond the pulmonary artery bifurcation. To determine the effect of pulmonary arterial denervation acute pulmonary hypertension was induced in 8 pigs by intravenous infusion of thromboxane A2 analogue. Animals were assigned to either pulmonary artery denervation, using a prototype radiofrequency catheter and generator, or a sham procedure. Pulmonary artery denervation resulted in reduced mean pulmonary artery pressure and pulmonary vascular resistance and increased cardiac output. Ablation lesions on the luminal surface of the pulmonary artery were accompanied by histological and biochemical alteration in adventitial nerves and correlated with improved hemodynamic parameters. Conclusions— Pulmonary artery denervation offers the possibility of a new treatment option for patients with pulmonary arterial hypertension. Further work is required to determine the long-term efficacy and safety. PMID:26553697

  19. Successful Treatment of Resistant Hypertension by Means of Chronic Renal Artery Occlusion Revascularization in a Fragile Patient

    PubMed Central

    Spezia, Laura; Perandini, Simone; Augelli, Raffaele; Puppini, Giovanni; Montemezzi, Stefania

    2016-01-01

    Summary Background Renal artery stenosis is a common cause of secondary hypertension refractory to medical therapy. Percutaneous angioplasty along with metallic stent placement has been described as an effective treatment for revascularization of the renal artery. Case Report A 54-year-old woman affected by paranoid schizophrenia with a history of hypertension and chronic renal failure due to renal artery occlusion was treated by endovascular recanalization and stent placement that resulted in improvement of renal function and control of hypertension. Laboratory studies 4 months after the revascularization revealed blood creatinine decrease gradually from 8.57 mg/dL to 3 mg/dL. Conclusions Revascularization with stenting has proven to be a safe and effective procedure in the treatment of total renal artery occlusion which also led to a significant relief at a psychological level. PMID:27882189

  20. Intra--and Intercellular Calcium Handling in Pulmonary Arterial Hypertension.

    PubMed

    Mouratoglou, Sophia-Anastasia; Giannakoulas, George; Deftereos, Spyridon; Giannopoulos, Georgios; Angelidis, Christos; Cleman, Michael W; Vassilikos, Vassilios P

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a serious life threatening disease that leads to right heart failure and death. Elevated pulmonary vascular resistance (PVR) is the main pathophysiological component that leads to elevated pulmonary arterial pressures and increased right ventricular afterload. Increased PVR is related to different mechanisms that include vasoconstriction, proliferative and obstructive remodeling of the pulmonary vessel wall and in situ thrombosis. Numerous molecular, genetic and humoral abnormalities have been proposed to play an important role in pulmonary vasoconstriction and remodeling. Of those, calcium (Ca(+2)) is a well recognized parameter involved in the pathogenetic mechanisms of PAH, because of its twofold role in both vasoconstriction and pulmonary artery smooth muscle cell (PASMC) proliferation. The aim of this review is to focus on Ca(+2) handling and dysregulation in PASMC of PAH patients.

  1. Pre-treatment considerations in childhood hypertension due to chronic kidney disease

    PubMed Central

    Olowu, Wasiu Adekunle

    2015-01-01

    Hypertension (HTN) develops very early in childhood chronic kidney disease (CKD). It is linked with rapid progression of kidney disease, increased morbidity and mortality hence the imperative to start anti-hypertensive medication when blood pressure (BP) is persistently > 90th percentile for age, gender, and height in non-dialyzing hypertensive children with CKD. HTN pathomechanism in CKD is multifactorial and complexly interwoven. The patient with CKD-associated HTN needs to be carefully evaluated for co-morbidities that frequently alter the course of the disease as successful treatment of HTN in CKD goes beyond life style modification and anti-hypertensive therapy alone. Chronic anaemia, volume overload, endothelial dysfunction, arterial media calcification, and metabolic derangements like secondary hyperparathyroidism, hyperphosphataemia, and calcitriol deficiency are a few co-morbidities that may cause or worsen HTN in CKD. It is important to know if the HTN is caused or made worse by the toxic effects of medications like erythropoietin, cyclosporine, tacrolimus, corticosteroids and non-steroidal anti-inflammatory drugs. Poor treatment response may be due to any of these co-morbidities and medications. A satisfactory hypertensive CKD outcome, therefore, depends very much on identifying and managing these co-morbid conditions and HTN promoting medications promptly and appropriately. This review attempts to point attention to factors that may affect successful treatment of the hypertensive CKD child and how to attain the desired therapeutic BP target. PMID:26558187

  2. Renal denervation for hypertension refractory to renal artery stenting.

    PubMed

    Bausback, Yvonne; Friedenberger, Josef; Hertting, Klaus; Werner, Martin; Branzan, Daniela; Freitas, Bruno; Piorkowski, Michael; Schmidt, Andrej; Scheinert, Dierk

    2014-04-01

    To investigate the effect of renal denervation (RDN) on blood pressure and renal function in refractory hypertension after renal artery recanalization and optimal medical therapy. Ten patients (6 women; mean age 70.0±5.1 years) with an office systolic blood pressure >160 mmHg despite taking ≥3 antihypertensive drugs and uni- or bilateral renal artery stenting were treated with RDN. Radiofrequency (RF) energy was delivered to the native segment of the artery keeping a 5-mm safe distance from the stented segments. Standardized office (OBP) and ambulatory (ABP) blood pressure measurements, medication, and renal assessment, including renal duplex ultrasound and renal function, were determined at baseline and on follow-up to 12 months. OBP (systolic/diastolic) at baseline was 190.0±20.4 / 84.2±10.1 mmHg. It decreased to 171.1±28.7* / 82.2±8.7, 165.5±28.4(†) / 76.1±7.4, and 158.3±14.2(†) / 75.5±9.5(†) mmHg (*p<0.001; (†)p<0.01) at 3, 6, and 12 months after RDN, respectively. Average ABP (systolic/diastolic) after 6 and 12 months decreased by -7.6(‡) / -3.1 and -11.3(‡) / -5.1(‡) mmHg ((‡)p<0.05). There was no renal artery (re)stenosis, dissection, or aneurysm within 12 months. Creatinine, cystatin C, and glomerular filtration rate remained unchanged. Urine albumin excretion decreased in 4/10 patients. Renal resistive indices improved in native, but not in stented renal arteries within the follow-up period. This proof-of-concept study demonstrates that RF-based RDN can be safely and effectively delivered in patients with resistant hypertension and previous renal artery stenting.

  3. Autoimmune disease mouse model exhibits pulmonary arterial hypertension.

    PubMed

    Sugimoto, Koichi; Nakazato, Kazuhiko; Sato, Akihiko; Suzuki, Satoshi; Yoshihisa, Akiomi; Machida, Takeshi; Saitoh, Shu-Ichi; Sekine, Hideharu; Takeishi, Yasuchika

    2017-01-01

    Pulmonary arterial hypertension is often associated with connective tissue disease. Although there are some animal models of pulmonary hypertension, an autoimmune disease-based model has not yet been reported. MRL/lpr mice, which have hypergammaglobulinemia, produce various autoimmune antibodies, and develop vasculitis and nephritis spontaneously. However, little is known about pulmonary circulation in these mice. In the present study, we examined the pulmonary arterial pressure in MRL/lpr mice. We used female MRL/lpr mice aged between 12 and 14 weeks. Fluorescent immunostaining showed that there was no deposition of immunoglobulin or C3 in the lung tissue of the MRL/lpr mice. Elevation of interferon-γ and interleukin-6 was recognized in the lung tissue of the MRL/lpr mice. Right ventricular systolic pressure, Fulton index and the ratio of right ventricular weight to body weight in the MRL/lpr mice were significantly higher than those in wild type mice with same background (C57BL/6). The medial smooth muscle area and the proportion of muscularized vessels in the lung tissue of the MRL/lpr mice were larger than those of the C57BL/6 mice. Western blot analysis demonstrated markedly elevated levels of prepro-endothelin-1 and survivin as well as decreased endothelial nitric oxide synthase phosphorylation in the lung tissue of the MRL/lpr mice. Terminal deoxynucleotidyl-transferase-mediated dUTP nick end-labeling assay showed the resistance against apoptosis of pulmonary arterial smooth muscle cells in the MRL/lpr mice. We showed that MRL/lpr mice were complicated with pulmonary hypertension. MRL/lpr mice appeared to be a useful model for studying the mechanism of pulmonary hypertension associated with connective tissue diseases.

  4. Hypoxia Does neither Stimulate Pulmonary Artery Endothelial Cell Proliferation in Mice and Rats with Pulmonary Hypertension and Vascular Remodeling nor in Human Pulmonary Artery Endothelial Cells

    PubMed Central

    Yu, Lunyin; Hales, Charles A.

    2011-01-01

    Background Hypoxia results in pulmonary hypertension and vascular remodeling due to induction of pulmonary artery cell proliferation. Besides pulmonary artery smooth muscle cells, pulmonary artery endothelial cells (PAECs) are also involved in the development of pulmonary hypertension, but the effect of hypoxia on PAEC proliferation has not been completely understood. Methods We investigated PAEC proliferation in mice and rats with hypoxia-induced pulmonary hypertension and vascular remodeling as well as in human PAECs under hypoxia. Results and Conclusion We did not find significant PAEC proliferation in chronically hypoxic rats or mice. There was a slight decrease in proliferation in mice and rats with pulmonary hypertension and vascular remodeling. We also did not find significant human PAEC proliferation and cell cycle progression under different levels of oxygen (1, 2, 3, 5 and 10%) for one day, although the same conditions of hypoxia induced significant proliferation and cell cycle progression in pulmonary artery smooth muscle cells and pulmonary artery fibroblasts. Exposure to hypoxia for 7 days also did not increase PAEC proliferation. These results demonstrated that hypoxia alone is not a stimulus to PAEC proliferation in vivo and in vitro. The present study provides a novel role for PAECs in hypoxia-induced pulmonary hypertension and vascular remodeling. PMID:21691120

  5. Renal artery stenosis due to neurofibromatosis type 1: case report and literature review

    PubMed Central

    2014-01-01

    Background Neurofibromatosis type 1 (NF1) is a relatively common autosomal dominant disorder. The most common vascular abnormality in patients with NF1 is bilateral or unilateral renal artery stenosis. Case report A 16-year-old boy presented with a headache of 4-year duration and was found to be moderately hypertensive. On physical examination, axillary freckling and multiple café-au-lait spots were revealed over the trunk, while numerous small nodules were palpable on the limbs. Biopsy of subcutaneous nodule showed neurofibroma. Lisch nodules were identified on slit-lamp examination and grade I hypertensive retinopathy was present on fundoscopy. Clinical laboratory investigations revealed that renal and liver function tests, blood cells count, urinalysis, serum electrolytes, serum levels of renin and aldosterone, and 24-hour urine levels of catecholamines were all within normal ranges. Abdominal ultrasound and CT were normal. Both kidneys were of normal size. CT angiography showed right renal artery stenosis (>90%) at the ostium. The final diagnosis of NF1 with right renal artery stenosis and secondary hypertension was then made. The patient was treated with Procardin (30 mg/d) and improved with a significant decline in blood pressure. The main outcomes were to control blood pressure without necessarily proceeding with PTRA. We also present a review of the literature. Conclusions NF1 may present with hypertension due to renal artery stenosis in children. All young patients (<30 year) with hypertension should be clinically screened for secondary causes of hypertension, including NF1, so that renal revascularization can be offered before permanent end organ damage has occurred. First-line management using medication alone could be appropriate, keeping the interventional options for when the patient's condition deteriorates. PMID:24678641

  6. Lineage Analysis in Pulmonary Arterial Hypertension

    DTIC Science & Technology

    2012-06-01

    cells that occlude the lumen of the microcirculation leading to right ventricular congestive failure and death. The neointimal cells express...disorganized fibrils of smooth muscle actin. The origin of the neointimal cells remains unresolved: the neointima may arise from de-differentiation of vascular...lead to death due to right ventricular failure (Lilienfeld and Rubin 2000, Rubin 1997). The pathology of PAH is characterized by abnormal expansions

  7. Increased mortality in African Americans with idiopathic pulmonary arterial hypertension.

    PubMed

    Davis, Kala K; Lilienfeld, David E; Doyle, Ramona L

    2008-01-01

    Idiopathic pulmonary arterial hypertension (IPAH) is a progressive disorder that usually culminates in right ventricular failure and death without treatment. To assess mortality trends by race and gender for idiopathic pulmonary arterial hypertension in the United States from 1994-1998. The U.S. National Center for Health Statistics data for the years 1994-1998 was reviewed for deaths in which the underlying cause was primary pulmonary hypertension (ICD-9 code 416.0), now known as IPAH. The age, gender, race and state of residence of the deceased were abstracted from the Centers for Disease Control Wonder System (http://wonder.cdc.gov). Average annual age-adjusted region-, race- and gender-specific rates were then calculated. African-American women demonstrated the highest mortality rates for IPAH across all age groups compared to other racial and gender groups. No geographical differences in mortality rates were noted. An increase in mortality rates with advancing age was observed in all racial and gender groups, with the highest mortality rates for IPAH noted in the elderly. African Americans with IPAH exhibit a substantially increased mortality compared with Caucasians, particularly African-American women.

  8. [Arterial hypertension in Croatia. Results of EH-UH study].

    PubMed

    Jelaković, Bojan; Zeljković-Vrkić, Tajana; Pećin, Ivan; Dika, Zivka; Jovanović, Aleksandar; Podobnik, Drina; Smuc, Tomislav; Gamberger, Dragan; Katić, Kristina; Kasner, Mario; Kuzmanić, Dusko

    2007-06-01

    Arterial hypertension (AH) is the most important independent risk factor of cardiovascular diseases. The prevalence of AH is higher than it was several decades before, and in Europe it is approximately 40%. A higher prevalence of AH has been reported in Europe than in the United States and Canada. According to the results of epidemiology of arterial hypertension in Croatia study (EH-UH), the prevalence of AH in Croatia is 37.5%. Women are more aware, they were treated more often, and blood pressure control was more frequently achieved than in men. However, body mass index and socioeconomic factors have a greater influence on blood pressure values and prevalence of AH in women. A low level of health education and inappropriate treatment are the most important reasons for the poor blood pressure control observed. Measures of primary prevention should be performed continuously and adjusted to special population subgroups. As an increase of obesity and hypertension was observed in school children, these measures should start at that age.

  9. Moderate exercise training reduces arterial chemoreceptor reflex drive in mild hypertension.

    PubMed

    Izdebska, E; Izdebski, J; Cybulska, I; Makowiecka-Ciesla, M; Trzebski, A

    2006-11-01

    The aim of our study was to check the responsiveness the chemoreceptor reflex in 28 young mildly hypertensive men (HTS), aged 18-32 years and 25 normotensive male subjects (NTS) aged 19-32 years, before and after 3-months dynamic exercise training. We tested the hypothesis that dynamic training reduces arterial chemoreceptor drive in mild hypertension. Circulatory response to 3-min hyperoxic inactivation of arterial chemoreceptors induced by 70% oxygen breathing was measured before and after training. Arterial blood pressure (BP) was recorded continuously by Finapres method, stroke volume and arm blood flow were registered by impedance reography, heart rate by ECG. Both groups were submitted to moderate 3-months dynamic exercise training. Before training the hyperoxic breathing caused in HTS a significant decrease in systolic BP by 6+/-1 mmHg p<0.01, in diastolic BP by 2+/-0.6 mmHg p<0.01, and in total peripheral vascular resistance (TPR) by 0.24+/-0.04 TPRU (p<0.01). After training hyperoxia augmented systolic BP by 2.64+/-1.9 mmHg (NS), diastolic BP by 2+/-1 mmHg p<0.05, and TPR by 0.043+/-0.05 TPRU (ANOVA). In NTS before training brief hyperoxia produced insignificant change in BP and TPR. In NTS after training hyperoxia increased systolic BP by 4.2 mm Hg+/-1.23 p<0.01 and diastolic BP by 3.1+/-0.6 mmHg p<0.01 respectively and TPR by 0.053+/-0.02 TPRU. Our results confirm earlier finding on the enhanced arterial chemoreceptor reflex drive in mild human hypertension. We conclude that normalizing arterial blood pressure in subjects with mild hypertension which occurred after 3-months dynamical exercise training is due to attenuation of the sympathoexcitatory chemoreceptor reflex drive by exercise training. The mechanism of this effect requires further study.

  10. Hyperuricemia, low urine urate excretion and target organ damage in arterial hypertension.

    PubMed

    Campo, Carlos; Ruilope, Luis M; Segura, Julian; Rodicio, José L; García-Robles, Rafael; Garcia-Puig, Juan

    2003-01-01

    Hyperuricemia can be the consequence of an increased urate production, a decreased renal excretion, or both. An increased prevalence of hyperuricemia has been described in essential hypertensive patients partly due to a decreased renal urinary urate excretion (UUE). Hyperuricemia has been shown to be associated with an increased risk of cardiovascular disease in hypertensive patients in some but not in all epidemiological studies in which this relationship has been investigated. To assess the influence of low UUE in the association between serum urate, renal function and hypertension severity. This cross-sectional study was carried out in a sample of 677 male hypertensive patients, aged 35-60 years, with essential arterial hypertension consecutively attended in a hospital hypertension unit. The presence of hypertension-related organ damage at diagnosis was classified according to classical WHO criteria as grade 1, 2 or 3. Urate underexcretion was defined as 24-h urinary urate below the product serum urate x 100. Mean serum urate levels were 6.4 +/- 1.6 mg/dl in the total sample. Hyperuricemia (serum urate >7 mg/dl) was present in 28.5% of patients and only 17.0% had underexcretory hyperuricemia. This subgroup of patients exhibited the higher rate of hypertension-related target organ damage (TOD). A multivariate analysis, showed that underexcretory hyperuricemia but not hyperuricemia remained an independent predictor of TOD (odds ratio 2.5. 95% CI 1.6-3.89). Serum urate correlated positively with serum creatinine in hyperuricemic patients (r = 0.50, p < 0.001), but not in patients with underexcretory hyperuricemia (r = 0.21, p = 0.18). Underexcretory hyperuricemia is strongly related to hypertensive organ damage and this relationship does not seem to be mediated by a decreased renal function. This aspect could underline the predictive value of hyperuricemia independently of serum creatinine. UUE could improve the clinical predictive value of hyperuricemia as a

  11. [The cost of arterial hypertension in Spain].

    PubMed

    Badía, X; Rovira, J; Tresserras, R; Trinxet, C; Segú, J L; Pardell, H

    1992-12-12

    High blood pressure has a high incidence and produces a high morbidity and mortality due to associated diseases: cerebrovascular disease, ischemic cardiopathy, and cardiac failure. The socioeconomic impact of high blood pressure in Spain was estimated during 1985 in primary, hospitalary and pharmaceutical health care, to provide a framework for decision making and to determine strategies for reducing the costs of this entity. The methodology of analysis of the cost of the disease was followed with the aim of quantifying the socioeconomic consequences of an entity, disease or risk factor with prevalence being the focus of the study. The socioeconomic impact estimated was situated between 95,000 and 124,000 millions of pesetas according to the different hypothesis adopted in the analysis of sensitivity. The direct health care costs represented between 2.6 and 3.9% of the global health care costs for Spain in 1985. Health care funding consumed by high blood pressure in primary health care was higher (between 4.5 and 6.7%) than hospital attendance (between 1.0 and 1.5%) and pharmaceutical care (between 2.3 and 3.5%), with respect to the total costs of each category. The reduction of the costs related with high blood pressure in Spain must be obtained from improvement of efficacy of interventions carried out in health care education and primary health care. The economic evaluation of the primary and secondary prevention programs may aid in determining more cost-effective strategies.

  12. Carvedilol inhibits proliferation of cultured pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension.

    PubMed

    Fujio, Hideki; Nakamura, Kazufumi; Matsubara, Hiromi; Kusano, Kengo Fukushima; Miyaji, Katsumasa; Nagase, Satoshi; Ikeda, Tetsuya; Ogawa, Aiko; Ohta-Ogo, Keiko; Miura, Daiji; Miura, Aya; Miyazaki, Masahiro; Date, Hiroshi; Ohe, Tohru

    2006-02-01

    Idiopathic pulmonary arterial hypertension (IPAH) is associated with proliferation of smooth muscle cells (SMCs) in small pulmonary arteries. Inhibition of proliferation of pulmonary artery smooth muscle cells (PASMCs) may be an effective treatment of patients with idiopathic pulmonary arterial hypertension. Recent studies have shown that carvedilol, an alpha- and beta-blocker with antioxidant and calcium channel blocking properties, inhibits the proliferation of cultured normal human pulmonary artery smooth muscle cells. In this study, we tested the hypothesis that carvedilol has antiproliferative effects on pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension. Pulmonary artery smooth muscle cells from six idiopathic pulmonary arterial hypertension patients who had undergone lung transplantation were cultured. To determine cell proliferation, H-thymidine incorporation was measured. Platelet-derived growth factor-induced proliferation of IPAH-PASMCs was significantly greater than that of normal control pulmonary artery smooth muscle cells. Carvedilol (0.1 microM to 10 microM) inhibited the proliferation of idiopathic pulmonary arterial hypertension-pulmonary artery smooth muscle cells in a concentration-dependent manner. Prazosin (an alpha-blocker) and N-acetyl L cysteine (an antioxidant agent) (0.1 microM to 10 microM) did not inhibit their proliferation, but the high concentration of propranolol (a beta-blocker) and nifedipine (a calcium channel blocker) (10 microM) inhibited the proliferation. The combination of propranolol and nifedipine inhibited the proliferation but only at a high concentration (10 microM) combination. Cell cycle analysis revealed that carvedilol (10 microM) significantly decreased the number of cells in S and G2/M phases. These results indicate that carvedilol inhibits the exaggerated proliferation of pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension

  13. Pulmonary Arterial Hypertension: A Focus on Infused Prostacyclins.

    PubMed

    Stewart, Traci

    2016-01-01

    Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and cell proliferation in the pulmonary vasculature. Guideline-driven interventions with infused prostacyclin treatment are the mainstay for patients with advanced symptoms. Infused prostacyclin therapy is complex. It is critical to manage prostacyclin therapy with precision because boluses or interruptions can be fatal. Education of patients and inpatient staff nurses is necessary to prevent negative outcomes. Nurses are an essential part of the multidisciplinary team caring for patients with PAH. The diagnostic evaluation and treatment of PAH are reviewed here, and challenges associated with the care of patients on prostacyclin therapy are discussed.

  14. Pulmonary arterial hypertension associated with neurofibromatosis type 1

    PubMed Central

    Carrascosa, Miguel F; Larroque, Isabel Celemín; Rivero, Juan-Luis García; García, José-Antonio Saiz-Quevedo; Hoz, Marta Cano; Ares, Miguel Ares; López, Xabier Arrastio; Caviedes, José-Ramón Salcines

    2010-01-01

    The authors report a case of severe pulmonary arterial hypertension (PAH) in a 75-year-old woman who had received a diagnosis of neurofibromatosis type 1 (NF1) 23 years before. She presented with progressive dyspnoea and recurrent syncope. Even though the patient initially improved after starting supportive and specific treatment for PAH, she then deteriorated and died from respiratory failure 11 months after the diagnosis of PAH. Prompt recognition of such an unusual association between PAH and NF1 and appropriate therapeutic intervention could ameliorate quality of life and prolong survival in this patient population. PMID:22798089

  15. Genomics of Pulmonary Arterial Hypertension: Implications for Therapy

    PubMed Central

    Geraci, Mark W.; Bull, Todd M.; Tuder, Rubin M.

    2009-01-01

    Synopsis Pulmonary arterial hypertension remains a vexing clinical disease with no cure. Despite advances and the discovery of a gene (BMPR2) associated with many of the hereditary forms of the disease, and some cases not previously known to be inherited, the reasons for mutations in this gene as a cause remain somewhat elusive. Clearly, a complex interplay exists between genetic alterations, environmental exposures (including infections) and disease development. This article addresses the advances in the genetics of PAH, including the identification of genetic etiologies and modulators, and the role of genetics in predicting disease progression and targeting therapeutics. PMID:19945066

  16. Therapies for scleroderma-related pulmonary arterial hypertension

    PubMed Central

    Hassoun, Paul M

    2009-01-01

    Pulmonary arterial hypertension (PAH), a common complication of systemic sclerosis, carries a very severe prognosis and is one of the leading causes of death in patients who suffer from it. Indeed, response to modern medical therapy has been disappointing in scleroderma-related PAH compared with other forms of PAH from the WHO group 1 classification of diseases, despite similar histological changes involving the pulmonary vasculature. This review discusses specific features of scleroderma-related PAH, currently available and US FDA-approved therapy for this syndrome, as well as potential future therapeutic developments based on newly acquired knowledge of this disorder. PMID:19885388

  17. The study of risk in pulmonary arterial hypertension.

    PubMed

    Rubin, Lewis J; Simonneau, Gerald; Badesch, David; Galiè, Nazzareno; Humbert, Marc; Keogh, Anne; Massaro, Joseph; Matucci Cerinic, Marco; Sitbon, Olivier; Kymes, Steven

    2012-09-01

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

  18. Responses of mean arterial pressure to pressor agents and diuretics in renal hypertensive and salt hypertensive rats

    PubMed Central

    Nicholas, T. E.

    1971-01-01

    1. The responses of the mean arterial pressure to (—)-noradrenaline, tyramine, angiotensin II-val5-amide, vasopressin and rat renin have been contrasted in renal hypertensive and in salt plus desoxycorticosterone hypertensive rats. The responses were measured in rats both unanaesthetized and rats anaesthetized with pentobarbitone. 2. Responses of unanaesthetized, ganglion blocked renal hypertensive rats to noradrenaline, tyramine and vasopressin markedly exceeded, and to angiotensin II and renin were markedly smaller than, those of unanaesthetized ganglion blocked salt + DOC hypertensive animals. Responses to angiotensin and to renin were apparently enhanced in the latter animals. 3. Hydrochlorothiazide and frusemide markedly reduced mean arterial pressure in salt + DOC hypertensive rats before and after ganglionic blockade. 4. Neither diuretic caused significant reduction in the mean arterial pressures of unanaesthetized, renal hypertensive rats in the absence of ganglionic blockade: frusemide did so in anaesthetized and unanaesthetized rats after ganglionic blockade. 5. Whereas the diuretics did not affect the responses of the renal hypertensive rats to pressor agents, frusemide and to a lesser extent hydrochlorothiazide tended to depress the responses to pressor agents in salt induced hypertension. 6. Hydrochlorothiazide did not influence mean arterial pressure in unanaesthetized rats with neurogenic hypertension. PMID:4326321

  19. [Image and hemodynamical features of pulmonary artery branches in COPD with pulmonary artery hypertension].

    PubMed

    Wang, Li-hua; Zhang, Wen-pu; Jiang, Wei-xiang; Qian, Yu-e

    2010-11-01

    To investigate the imaging and hemodynamical features of pulmonary artery branches in chronic obstructive pulmonary disease (COPD) with pulmonary artery hypertension (PAH). CT pulmonary angiography (CTPA) with ECG-gating was performed in 13 patients with clinical diagnosed COPD and 25 normal subjects. The thin-slice multiple plane reconstruction in systole and diastole phase was conducted, which in turn was used to generate the InSpace reconstructed images with reference frame of the main pulmonary artery and the first two grades branches, the contour of the branches was depicted. On the base of coordinates, the GAMBIT was used to generate nodes and furthermore meshes, then the software Fluent was used for numerical calculation and flow simulation. The velocity and pressure changes in the main pulmonary artery and the first two grades branches during different periods of cardiac cycle were observed in both groups. CTPA showed that the diameter of the main pulmonary before bifurcate and proximal of the first two branches was larger in systole period than that in diastole period. The diameter of the second segmental artery of right upper lobe was larger during diastole period. The length of the main pulmonary and the first two branches showed no significant difference in both diastole and systole periods. There was no significant difference in length of pulmonary arteries between COPD and normal groups. The main pulmonary to distal right pulmonary artery appeared larger in diastole period. Compared with normal, in COPD group several arteries increased in diameter including proximal and distal of the proximal right pulmonary artery and the proximal right pulmonary artery during systole and diastole periods. In systole period only the diameter of the main pulmonary before bifurcate got larger and the back basic segmental artery of both lower lobe show smaller than normal. The flow condition analysis in COPD and normal groups suggested higher pressure in pulmonary

  20. Successful endovascular treatment of hemosuccus pancreaticus due to splenic artery aneurysm associated with segmental arterial mediolysis.

    PubMed

    Obara, Hideaki; Matsubara, Kentaro; Inoue, Masanori; Nakatsuka, Seishi; Kuribayashi, Sachio; Kitagawa, Yuko

    2011-11-01

    Hemosuccus pancreaticus, which is generally due to the rupture of a splenic artery aneursym into the pancreatic duct, is a rare cause of intermittent upper gastrointestinal hemorrhage. Segmental arterial mediolysis (SAM) is a rare arteriopathy. We report a 53-year-old man with hemosuccus pancreaticus due to a splenic artery aneurysm associated with SAM. The patient, who also had a celiac artery aneurysm affected by SAM, was successfully treated by both coil embolization and aortic stent grafting for complete coverage of the celiac artery. SAM is a very rare cause of hemosuccus pancreaticus, and endovascular treatment may be favorable for hemosuccus pancreaticus.

  1. Distinctive metabolomic fingerprint in scleroderma patients with pulmonary arterial hypertension.

    PubMed

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

    2017-08-15

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

  2. Prognostic significance of small-artery structure in hypertension.

    PubMed

    Rizzoni, Damiano; Porteri, Enzo; Boari, Gianluca E M; De Ciuceis, Carolina; Sleiman, Intissar; Muiesan, Maria Lorenza; Castellano, Maurizio; Miclini, Marco; Agabiti-Rosei, Enrico

    2003-11-04

    The presence of structural alterations in the microcirculation may be considered an important mechanism of organ damage; however, it is not currently known whether structural alterations of small arteries may predict fatal and nonfatal cardiovascular events. One hundred twenty-eight patients were included in the present study. There were 59 patients with essential hypertension, 17 with pheochromocytoma, 20 with primary aldosteronism, 12 with renovascular hypertension, and 20 normotensive patients with non-insulin-dependent diabetes mellitus. All subjects were submitted to a biopsy of subcutaneous fat. Small resistance arteries were dissected and mounted on an isometric myograph, and the tunica media-to-internal lumen ratio (M/L) was measured. The subjects were reevaluated after an average follow-up time of 5.4 years. Thirty-seven subjects had a documented fatal or nonfatal cardiovascular event (5.32 events/100 patients per year). In the subcutaneous small arteries of subjects with cardiovascular events, a smaller internal diameter and a clearly greater M/L was observed. Our subjects were subdivided according to the presence of an M/L greater or smaller than the mean and median values observed in the whole population (0.098) or mean value +2 SD of our normal subjects (0.11). Life-table analyses showed a significant difference in event-free survival between the subgroups. Cox's proportional hazard model, considering all known cardiovascular risk factors, indicated that only pulse pressure (P=0.009) and M/L (P<0.0001) were significantly associated with the occurrence of cardiovascular events. Our results strongly indicate a relevant prognostic role of structural alterations in small resistance arteries of a high-risk population.

  3. [Hemodynamics during long-term combination therapy of arterial hypertension].

    PubMed

    Wiechmann, H W; Schuster, P; Sturm, A

    1985-04-12

    In 20 patients with essential arterial hypertension, grade II or III, the haemodynamic effect of a fixed combination of antihypertensive drugs (bemetizide, triamteren, bupranolol and dihydralazine) was studied by percutaneously-introduced flow-guided catheter in the pulmonary artery before, after three weeks and at the end of a six-month period of treatment; systemic arterial blood pressures were measured by the cuff method. Mean pressures, both at rest and on exercise were significantly and persistently lowered. Mean blood pressure at rest fell from 184/110 mmHg before treatment to 167/98 mmHg after three weeks, and to 158/93 mmHg after six months. The initial blood pressure on exercise was 226/129 mmHg, which fell after three weeks to 199/113 mmHg and after six months to 190/106 mmHg. At the same time, pulmonary artery pressure (as a measure of preload) fell by 23% at rest and 30% on exercise. Exercise tolerance of the patients rose by 28%. Pressure-heartrate product fell by 18%, as a pointer to an additional favourable effect on left ventricular oxygen consumption.

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

    PubMed Central

    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

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

    PubMed Central

    Palatini, Paolo; Casiglia, Edoardo; Gąsowski, Jerzy; Głuszek, Jerzy; Jankowski, Piotr; Narkiewicz, Krzysztof; Saladini, Francesca; Stolarz-Skrzypek, Katarzyna; Tikhonoff, Valérie; Van Bortel, Luc; Wojciechowska, Wiktoria; Kawecka-Jaszcz, Kalina

    2011-01-01

    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 reduction. Although many methodological problems still hinder the wide clinical application of parameters of arterial stiffness, these will likely contribute to cardiovascular assessment and management in future clinical practice. Each of the abovementioned parameters reflects a different characteristic of the atherosclerotic process, involving functional and/or morphological changes in the vessel wall. Therefore, acquiring simultaneous measurements of different parameters of vascular function and structure could theoretically enhance the power to improve risk stratification. Continuous technological effort is necessary to refine our methods of investigation in order to detect early arterial abnormalities. Arterial stiffness and its consequences represent the great challenge of the twenty-first century for

  6. [Tunnelled central venous line-associated infections in patients with pulmonary arterial hypertension treated with intravenous prostacyclin].

    PubMed

    Boucly, Athénaïs; O'Connell, Caroline; Savale, Laurent; O'Callaghan, Dermot S; Jaïs, Xavier; Montani, David; Humbert, Marc; Simonneau, Gérald; Sitbon, Olivier

    2016-01-01

    Intravenous prostacyclins are a valuable treatment for patients with severe pulmonary arterial hypertension, leading to improved exercise capacity, haemodynamics, quality of life and survival. Unfortunately, due to the short half-life of these drugs, they need to be administered continuously through central venous catheters. Despite aseptic technique, regular dressing changes, tunneled central venous catheters and patient education, patients are exposed to central venous catheter associated infections. These infections cause significant morbidity and mortality. The clinical presentation, microbiology, consequences and management of these central venous catheter associated infections in pulmonary arterial hypertension patients treated with intravenous prostacyclins are discussed.

  7. [Daily profile of arterial pressure in patients with arterial hypertension, continuously living in Tyumen polar region].

    PubMed

    Gapon, L I; Sereda, T V; Shurkevich, N P; Shanaurina, N V

    2003-01-01

    To study a 24-h profile of arterial hypertension and affection of target organs in hypertensive population of the Tyumen North. 62 patients (43 men and 19 women, age 18-50 years) with arterial hypertension (AH) living in the North of the Tyumen region entered the test group. The control group consisted of 56 AH patients (36 men and 20 women) matched by age. They lived in the zone of moderate climate (in Tyumen). 24-h arterial pressure (AP) monitoring was made starting on day 2 of the patients' arrival in Tyumen. Echocardiography was made on the arrival day. The examination of the groups was conducted against "clean" background. The groups did not differ significantly by age, sex, AH duration, office systolic and diastolic pressure (SP, DP). However, 37 patients from the test group on arrival in Tyumen showed normalization of both office AP and mean 24-h AP. 25 patients from this group sustained high office and mean 24-h AP. An abnormal 24-h AP profile with nocturnal hypertension was recorded in 76.6% of the test group and 28.31% patients of the control group. Left ventricular hypertrophy was significantly more pronounced in the test group than in the control one. In 2/3 patients from the North with AH stage 1 and 2 office AP and mean 24-h AP normalized upon their arrival to the zone of moderate climate but their left ventricular hypertrophy was more severe and changes in a 24-h AP profile with nocturnal hypertension persisted.

  8. Left Atrial Area and Right Ventricle Dimensions in Non-gated Axial Chest CT can Differentiate Pulmonary Hypertension Due to Left Heart Disease from Other Causes.

    PubMed

    Katikireddy, Chandra K; Singh, Manmeet; Muhyieddeen, Kamil; Acharya, Tushar; Ambrose, John A; Samim, Arang

    2016-01-01

    It is unknown whether axial non-gated CT can distinguish World Health Organization Group 2 pulmonary hypertension (pulmonary hypertension due to left heart disease) from non-Group 2 pulmonary hypertension. The study was performed to identity imaging parameters in non-gated chest CT that differentiate Group 2 from non-Group 2 pulmonary hypertension. Among 158 patients who underwent right heart catheterization for evaluation of pulmonary hypertension, 112 had sufficient data and chest CT for review. Invasive hemodynamic data and numerous variables obtained from axial CT images (maximum diameters of main, right, left pulmonary arteries, ascending aorta, main pulmonary artery to ascending aorta diameter ratio, right atrial diameter, left atrial area and right ventricular size) were collected. CT variables were validated against hemodynamic data to identify parameters that would allow to differentiate pulmonary hypertension due to left heart disease (Group 2) from non-Group 2 pulmonary hypertension. Based on right heart catheterization data, we identified 53 patients with Group 2 pulmonary hypertension, 50 patients with non-Group 2 pulmonary hypertension, and 9 subjects with no pulmonary hypertension. In patients with a dilated pulmonary artery (n = 84), the ROC curve for left atrial area (area under the ROC curve 0.76 ± 0.06) independently distinguished patients with Group 2 pulmonary hypertension (n = 42) from patients with non-Group 2 pulmonary hypertension (n = 42). A dilated left atrium (>20 mm(2)) in combination with a normal right ventriuclar size had a sensitivity of 77% and specificity of 94% for Group 2 pulmonary hypertension. In patients with a dilated pulmonary artery on chest CT, left atrial area and right ventricular dimensions may aid to diagnose pulmonary hypertension and to distinguish underlying cardiac disease from other causes. Published by Elsevier Inc.

  9. Arterial hypertension and cardiovascular damage in the elderly: focus on arterial stiffness and left ventricular hypertrophy.

    PubMed

    Paciaroni, E; Antonicelli, R; Gambini, C; Sirolla, C

    1993-01-01

    Both aging and Arterial Hypertension (AH) cause a series of structural and functional changes in the cardiovascular apparatus. The reduction of aortic distensibility (RAD) and left ventricular hypertrophy (LVH) are, in particular, two significant markers of cardiovascular damage apart from being factors of serious and widespread morphological alterations. In this paper, the Authors analyze the effects of aging and of AH on the cardiovascular apparatus in order to find a possible clinical significance in relation to both RAD and LVH.

  10. [Ten years' experience in continuous intravenous epoprostenol therapy in severe pulmonary arterial hypertension].

    PubMed

    Pombo Jiménez, Marta; Escribano Subías, Pilar; Tello de Meneses, Rocío; Gómez-Sánchez, Miguel Angel; Delgado Jiménez, Juan; Dalmau González-Gallarza, Regina; Lázaro Salvador, María; Hernández Rodríguez, Isidro; Tascón Pérez, Juan; Sáenz de la Calzada, Carlos

    2003-03-01

    Primary pulmonary hypertension and its associated forms is a progressive and often fatal disease, the course of which has been favourably modified by prostacyclin therapy in the last decade. The aim of this study is to analize retrospectively the efficacy of continuous intravenous epoprostenol (synthetic prostacyclin) therapy in pulmonary arterial hypertension, and to compare it with conventional therapy (anticoagulants, digoxin and diuretics). Between 1990-2000, 31 patients with severe precapillary pulmonary hypertension in functional class III or IV went on continuous intravenous epoprostenol therapy, administered by a portable infusion pump through a Hickman catheter. We compared their survival with a group of 16 patients treated with conventional therapy alone. Time of follow-up was 33.25 months in the prostacyclin group and 20 months in the conventional group. The one- three- and five- year survival rates were 86%, 50% and 38% respectively for patients treated with epoprostenol compared with 40%, 40% and 8% survival rates at idetical periods for patients treated conventionally (p = 0,02). Functional class and the mean distance walked in the 6 minutes test were improved in patients treated with prostacyclin (p < 0,01). Serious complications attributable to the delivery system included 3 deaths, mainly due to infection. Continuous intravenous epoprostenol therapy improves survival and exercise capacity in patients with severe pulmonary arterial hypertension despite potentially serious complications attributable to the delivery system.

  11. Right ventricular diastolic dysfunction in arterial systemic hypertension: analysis by pulsed tissue Doppler.

    PubMed

    Cicala, S; Galderisi, M; Caso, P; Petrocelli, A; D'Errico, A; de Divitiis, O; Calabrò, R

    2002-06-01

    This study analyses right ventricular longitudinal function in arterial systemic hypertension by pulsed tissue Doppler. Thirty normotensives and 30 hypertensives, free of cardiac drugs, underwent standard Doppler echocardiography and pulsed tissue Doppler of right ventricular lateral tricuspid annulus and left ventricular lateral mitral annulus. By tissue Doppler, systolic and diastolic measurements were obtained. Hypertensives had higher left ventricular mass and impaired Doppler diastolic indexes, without changes of global systolic function. Tissue Doppler showed reduction of right ventricular E/A ratio and prolongation of relaxation time in comparison with controls (both P<0.00001). In the overall population, the length of tissue Doppler derived right ventricular relaxation time was positively related to right ventricular anterior wall thickness while right ventricular E/A ratio was positively related to E/A ratio of left ventricular mitral annulus (both P<0.00001). These relations remained significant even after adjusting for clinical and echocardiographic confounders by separate multivariate models. Arterial systemic hypertension is associated to right ventricular longitudinal diastolic dysfunction. This dysfunction involves the prolongation of active relaxation, which is independently associated with the degree of right ventricular hypertrophy and the impairment of passive wall properties, which is mainly due to ventricular interaction occurring under left ventricular pressure overload conditions. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.

  12. [Renovascular hypertension due to Takayasu arteritis--a case report].

    PubMed

    Galesić, Kresimir; Morović-Vergles, Jadranka; Zivko, Marijana; Racić, Ivana; Vergles, Domagoj; Borković, Zdravko; Cikes, Nada

    2005-01-01

    A 18-year old women with bilateral renal artery stenosis and renovascular hypertension as a part of Takayasu's disease is presented. Takayasu's disease is a chronic arteritis of unknown origin, primary affecting aorta and its branches. The disease is the most common in young women and is more common in the countries of eastern Asia in comparison with Western countries. Takayasu's disease can be severe and lifetreating disease. Mortality and morbidity depend on both the direct effect of the vascular lesions and the complications od disease. The mainstay of Takayasu's disease is based on the use of glucocorticoids alone or in association with cytotoxic drugs (cyclofosfamid, azatioprin, metotrexate). In the majority of cases, the partial control of disease is obtained.

  13. [French as 2005-recommendations on the management of arterial hypertension].

    PubMed

    Chamontin, B; Halimi, J M

    2007-01-01

    Self blood pressure measurements (home BP) and/or ambulatory BP measurements are recommended in mild to moderate hypertension (140/90 - 179/109 mmHg) in order to confirm sustained hypertension and identify white coat and masked hypertension. The evaluation of target organ damages (TOD) has to be integrated in cardiovascular risk estimate and taken into account in the management of hypertensive patients. Beside echocardiography, there is a place for the screening of microalbuminuria in non diabetic hypertensive patients, but these investigations should not be performed systematically. Arterial stiffness evaluation and carotid intima-media thickness quantification are not yet recommended. Cardiovascular risk (CV risk) estimate plays a pivotal role in the therapeutic decision and strategy. The cardiovascular risk grade is based on [1] the list of cardiovascular risk factors (same list AFSSAPS recommendations on dyslipidemia), [2] the presence or absence of TOD and [3] cardiovascular complications: "low", "medium", and "high" CV risk. Lifestyle modifications are recommended in all hypertensive patients. Five antihypertensive drugs are recommended for first line therapy: beta-blockers, thiazide diuretics, ACEIs, ARA II and CCBs (and fixed low dose combinations with AFSSAPS agreement for first line). In order to initiate the treatment, Evidence-based therapy (according to clinical trials conducted in different clinical situations), certain comorbid conditions (compelling indications), efficacy and side-effects in a previous experience, and the cost are the determinants of the first choice. Most hypertensive patients require more than one agent to achieve target blood pressure and for second line therapy the recommended combinations are: betablockers-diuretics, ACEIs-diuretics, ARAII-diuretics, betablockers-CCBs (DHP), ACEIs-CCBs, ARA II-CCBs and CCBs-diuretics. The delay to establish a combination therapy depend on CV risk. The BP goals are those recommended by ESH

  14. Role of oxidized lipids in pulmonary arterial hypertension

    PubMed Central

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

    2016-01-01

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

  15. Ambrisentan for the treatment of pulmonary arterial hypertension: improving outcomes

    PubMed Central

    Elshaboury, Soha M; Anderson, Joe R

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature that is associated with severe functional impairment and a poor prognosis. Ambrisentan is a selective endothelin type A receptor antagonist approved for the treatment of patients with PAH World Health Organization group 1. The efficacy and safety of ambrisentan has been evaluated in the ARIES series (Ambrisentan for the Treatment of Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Studies), which has established its use as both monotherapy or in conjunction with other PAH therapies. Specifically, ambrisentan is effective at increasing exercise tolerance, decreasing the risk of functional class deterioration, and prolonging time to clinical worsening. Further, ambrisentan has a favorable effect on mortality, with an 88% patient survival rate after two years of therapy compared with a 61% survival rate as estimated by the National Institute of Health Registry. Ambrisentan is generally well tolerated in all patient groups, with the main side effects of peripheral edema, sinusitis, flushing, and nasal congestion considered to be mild to moderate in nature. Ambrisentan has several favorable qualities that potentially make it more acceptable to patients, including once-daily administration, limited adverse drug reactions and drug-drug interactions, and minimal risk of liver enzyme elevation. Because of the potential risk of teratogenicity associated with ambrisentan, it is only available through a limited distribution program, ie, LEAP (the Letairis Education and Access Program). Ongoing clinical trials will help to clarify the role of ambrisentan in the treatment of PAH. PMID:23674888

  16. Pulmonary arterial hypertension in SLE: what do we know?

    PubMed

    Prabu, A; Gordon, C

    2013-10-01

    Pulmonary hypertension (PH) can occur at any time during the course of systemic lupus erythematosus (SLE), and can be independent of lupus disease activity in other systems. The pathogenesis of PH in SLE can be multifactorial, but pulmonary arterial hypertension (PAH) is the commonest cause of PH in SLE. The international PH registries have published that approximately 15% of connective tissue disease-associated PH is lupus related in their cohorts. As the symptoms of PH in SLE can be mild and non-specific in early stages, an increasing awareness of this devastating complication is essential for early diagnosis. Echocardiographic evaluation of several right heart variables in addition to systolic pulmonary artery pressure estimation reduces false positive rates for PH detection. Antiphospholipid antibodies may predict SLE-PAH. Prompt treatment of PAH with newer PAH therapy as well as immunosuppression can reduce morbidity and prolong survival. The survival in SLE-associated PAH is better compared with systemic sclerosis-associated PH but worse than idiopathic PAH. Pregnancy in SLE-PAH can result in a fatal outcome, especially in severe and poorly controlled PH at onset.

  17. Novel Approaches to Treat Experimental Pulmonary Arterial Hypertension: A Review

    PubMed Central

    Umar, S.; Steendijk, P.; Ypey, D. L.; Atsma, D. E.; van der Wall, E. E.; Schalij, M. J.; van der Laarse, A.

    2010-01-01

    Background. Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by an increase in pulmonary artery pressure leading to right ventricular (RV) hypertrophy, RV failure, and ultimately death. Current treatments can improve symptoms and reduce severity of the hemodynamic disorder but gradual deterioration in their condition often necessitates a lung transplant. Methods and Results. In experimental models of PAH, particularly the model of monocrotaline-induced pulmonary hypertension, efficacious treatment options tested so far include a spectrum of pharmacologic agents with actions such as anti-mitogenic, proendothelial function, proangiogenic, antiinflammatory and antioxidative. Emerging trends in PAH treatment are gene and cell therapy and their combination, like (progenitor) cells enriched with eNOS or VEGF gene. More animal data should be collected to investigate optimal cell type, in vitro cell transduction, route of administration, and number of cells to inject. Several recently discovered and experimentally tested interventions bear potential for therapeutic purposes in humans or have been shown already to be effective in PAH patients leading to improved life expectation and better quality of life. Conclusion. Since many patients remain symptomatic despite therapy, we should encourage research in animal models of PAH and implement promising treatments in homogeneous groups of PAH patients. PMID:20339474

  18. Arginase inhibitor attenuates pulmonary artery hypertension induced by hypoxia.

    PubMed

    Chu, YanBiao; XiangLi, XiaoYing; Niu, Hu; Wang, HongChao; Jia, PingDong; Gong, WenBin; Wu, DaWei; Qin, WeiDong; Xing, ChunYan

    2016-01-01

    Hypoxia-induced pulmonary arterial hypertension (HPAH) is a refractory disease characterized by increased proliferation of pulmonary vascular smooth cells and progressive pulmonary vascular remodeling. The level of nitric oxide (NO), a potential therapeutic vasodilator, is low in PAH patients. L-arginine can be converted to either beneficial NO by nitric oxide synthases or to harmful urea by arginase. In the present study, we aimed to investigate whether an arginase inhibitor, S-(2-boronoethyl)-L-cysteine ameliorates HPAH in vivo and vitro. In a HPAH mouse model, we assessed right ventricle systolic pressure (RVSP) by an invasive method, and found that RSVP was elevated under hypoxia, but was attenuated upon arginase inhibition. Human pulmonary artery smooth muscle cells (HPASMCs) were cultured under hypoxic conditions, and their proliferative capacity was determined by cell counting and flow cytometry. The levels of cyclin D1, p27, p-Akt, and p-ERK were detected by RT-PCR or Western blot analysis. Compared to hypoxia group, arginase inhibitor inhibited HPASMCs proliferation and reduced the levels of cyclin D1, p-Akt, p-ERK, while increasing p27 level. Moreover, in mouse models, compared to control group, hypoxia increased cyclin D1 expression but reduced p27 expression, while arginase inhibitor reversed the effects of hypoxia. Taken together, these results suggest that arginase plays an important role in increased proliferation of HPASMCs induced by hypoxia and it is a potential therapeutic target for the treatment of pulmonary hypertensive disorders.

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

    PubMed

    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

  20. [Effect of complex sanatorium treatment including magnetotherapy on hemodynamics in patients with arterial hypertension].

    PubMed

    Efremushkin, G G; Duruda, N V

    2003-01-01

    Forty nine patients with arterial hypertension of stage I-II received combined sanatorium treatment. Of them, 21 had adjuvant total magnetotherapy. All the patients were examined for parameters of central, cerebral hemodynamics and microcirculation. The adjuvant magnetotherapy produced a beneficial effect on hypertension: clinical symptoms attenuated, arterial pressure became more stable, hemodynamics improved, duration of hospitalization reduced, requirement in hypotensive drugs diminished.

  1. Arterial hypertension in the female world: pathophysiology and therapy.

    PubMed

    Cadeddu, Christian; Franconi, Flavia; Cassisa, Laura; Campesi, Ilaria; Pepe, Alessia; Cugusi, Lucia; Maffei, Silvia; Gallina, Sabina; Sciomer, Susanna; Mercuro, Giuseppe

    2016-04-01

    Hypertension is a major risk factor for cardiovascular disease and outcomes in women, and antihypertensive therapy is not always successful in achieving control over the blood pressure (BP). Nonoptimal control of BP remains a crucial risk factor for cardiovascular mortality, and in women, it could be related to sex-specific factors. Historically, women have been under-represented in clinical trials; therefore, the benefits of clinical outcomes and the safety profiles of antihypertensive therapies have been studied less extensively in women. The reasons for the sex differences in BP levels are multifactorial, implying different roles of the sex hormones, the renin-angiotensin system, sympathetic activity, and arterial stiffness. A complete understanding of the pathophysiological features of these differences requires further investigation.Nevertheless, the prevalence of the use of antihypertensive agents is higher among middle-aged women than among men. Notably, in the United States, hypertensive women use more diuretics and angiotensin receptor blockers than men, whereas hypertensive men more often receive beta-blockers, calcium channel antagonists, or inhibitors of angiotensin-converting enzyme. To date, the explanations for these sex differences in the consumption of antihypertensive drugs remain unknown.

  2. Treatment of hypertension in patients with atherosclerotic renal artery stenosis, updated.

    PubMed

    Chrysant, Steven G

    2014-11-01

    Atherosclerotic renal artery stenosis (ARAS) is a fairly common disease of elderly patients and is discovered incidentally in 6.3% to 38% in those undergoing diagnostic cardiac or abdominal angiography. Of those patients diagnosed with renal artery stenosis, in 90% it is due to ARAS and in 10% to fibromuscular dysplasia (FMD), which is a disease of younger persons, mostly females. Renal artery stenosis is frequently associated with hypertension and impaired renal function, and it is perceived by many physicians as the primary cause of hypertension and renal failure. For this reason, they believe that hypertension and renal failure can be significantly improved by performing percutaneous transluminal renal angioplasty (PTRA) with a stent placement as the preferred treatment instead of medical therapy. This practice has led to an increase in angioplasties, especially by interventional cardiologists who are familiar with the procedure. However, the results of several randomized studies comparing interventional therapy with medical therapy have shown no significant difference between the 2 treatment modalities in blood pressure reduction and prevention and in worsening of renal function. Similar results have been found by nonrandomized trials in patients treated selectively with PTRA. For this review, a Medline search was conducted of the English-language literature from January 1, 2006 to December 31, 2013, using the terms atherosclerotic renal artery stenosis and renal artery stenosis; 6 pertinent randomized studies were selected. These studies, with collateral literature, are discussed in this review. The data show that PTRA with stent plus medical therapy in patients with ARAS is not superior to medical therapy alone in lowering the blood pressure, in preventing renal function deterioration, and in reducing all-cause mortality, cardiovascular morbidity or mortality, and strokes.

  3. Arterial stiffness, antiphospholipid antibodies, and pulmonary arterial hypertension in systemic lupus erythematosus.

    PubMed

    Lee, Ji Hyun; Im Cho, Kyoung

    2014-12-01

    The aim of this study is to evaluate the role of arterial stiffness in pulmonary arterial hypertension (PAH) in systemic lupus erythematosus (SLE) patients and its relationship with antiphospholipid antibody (aPL). Measurement of brachial ankle pulse wave velocity (baPWV), carotid arterial stiffness, and pulmonary vascular resistance (PVR) was performed in 51 patients with SLE. PAH was diagnosed if the pulmonary artery systolic pressure was >40mmHg. Information concerning SLE duration, medication, and serum autoantibodies was recorded. SLE activity was assessed by the SLE disease activity index (SLEDAI). aPL was present in 10 patients (20%), and PAH was detected in 6 patients (12%). The prevalence of Raynaud's phenomenon, baPWV, positive aPL, and titers of IgG anticardiolipin antibody (aCL) were increased in SLE with PAH; however, no difference was found in inflammatory markers, disease duration, and SLEDAI compared to SLE without PAH. Carotid artery deformation and right ventricular function were reduced in patients with PAH (all p<0.05). Carotid artery circumferential strain (r=0.34, p=0.021), radial strain (r=-0.30, p=0.045), and baPWV (r=0.46, p=0.001) showed significant correlation between IgG aCL. Univariate and multiple regression analysis revealed that the only significant independent predictors of the presence of PAH were baPWV, carotid artery stiffness, and IgG aCL. Arterial stiffness might contribute to the pathogenesis of PAH related to SLE as well as aPLs. Furthermore, the significant association of aPL with arterial stiffness suggests its important role in PAH with SLE. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  4. Galectin-3 inhibition ameliorates hypoxia-induced pulmonary artery hypertension

    PubMed Central

    Hao, Mingwen; Li, Miaomiao; Li, Wenjun

    2016-01-01

    Galectin-3 (Gal-3) is a β-galactoside-binding lectin, which is important in inflammation, fibrosis and heart failure. The present study aimed to investigate the role and mechanism of Gal-3 in hypoxia-induced pulmonary arterial hypertension (PAH). Male C57BL/6J and Gal-3−/− mice were exposed to hypoxia, then the right ventricular systolic pressure (RVSP) and Fulton's index were measured, and Gal-3 mRNA and protein expression in the pulmonary arteries was analyzed by reverse transcription-quantitative polymerase chain reaction and western blotting. Compared with the control, hypoxia increased the mRNA and protein expression levels of Gal-3 in wild type murine pulmonary arteries. Gal-3 deletion reduced the hypoxia-induced upregulation of RVSP and Fulton's index. Furthermore, human pulmonary arterial endothelial cells (HPAECs) and human pulmonary arterial smooth muscle cells (HPASMCs) were stimulated by hypoxia in vitro, and Gal-3 expression was inhibited by small interfering RNA. The inflammatory response of HPAECs, and the proliferation and cell cycle distribution of HPASMCs was also analyzed. Gal-3 inhibition alleviated the hypoxia-induced inflammatory response in HPAECs, including tumor necrosis factor-α and interleukin-1 secretion, expression of intercellular adhesion molecule-1 and adhesion of THP-1 monocytes. Gal-3 inhibition also reduced hypoxia-induced proliferation of HPASMCs, partially by reducing cyclin D1 expression and increasing p27 expression. Furthermore, Gal-3 inhibition suppressed HPASMC switching from a ‘contractile’ to a ‘synthetic’ phenotype. In conclusion, Gal-3 serves a fundamental role in hypoxia-induced PAH, and inhibition of Gal-3 may represent a novel therapeutic target for the treatment of hypoxia-induced PAH. PMID:27959409

  5. Respiratory muscle dysfunction in idiopathic pulmonary arterial hypertension.

    PubMed

    Meyer, F J; Lossnitzer, D; Kristen, A V; Schoene, A M; Kübler, W; Katus, H A; Borst, M M

    2005-01-01

    Idiopathic pulmonary arterial hypertension (IPAH) is a pulmonary vasculopathy of unknown aetiology. Dyspnoea, peripheral airway obstruction and inefficient ventilation are common in IPAH. Data on respiratory muscle function are lacking. This prospective single-centre study included 26 female and 11 male patients with IPAH in World Health Organization functional classes II-IV. Mean+/-SD pulmonary artery pressure was 48.6+/-16.9 in females and 53.1+/-22.9 mmHg in males; cardiac output was 3.7+/-1.3 and 4.2+/-1.7 L x min(-1). Maximal inspiratory pressure (PI,max) was lower in the female patients than in 20 controls (5.3+/-2.0 versus 8.2+/-2.0 kPa). In the male patients, PI,max was lower than in 25 controls (6.8+/-2.2 versus 10.5+/-3.7 kPa). Maximal expiratory pressure (PE,max) was lower in the female patients than in controls (6.2+/-2.6 versus 9.5+/-2.1 kPa), and in male patients as compared to controls (7.1+/-1.6 versus 10.3+/-3.9 kPa). There was no correlation between PI,max or PE,max and parameters of pulmonary haemodynamics or exercise testing. The ratio of mouth occlusion pressure within the first 0.1 s of inspiration and PI,max was higher in IPAH than in controls (females 0.067+/-0.066 versus 0.021+/-0.008; males 0.047+/-0.061 versus 0.023+/-0.016). In conclusion, this study provides the first evidence of inspiratory and expiratory muscle weakness in idiopathic pulmonary arterial hypertension. The pathomechanisms and the prognostic significance should be further investigated.

  6. Predicting Stroke Risk in Hypertensive Patients With Coronary Artery Disease

    PubMed Central

    Coca, Antonio; Messerli, Franz H.; Benetos, Athanase; Zhou, Qian; Champion, Annette; Cooper-DeHoff, Rhonda M.; Pepine, Carl J.

    2009-01-01

    Background and Purpose Our understanding of factors influencing stroke risk among patients with coronary artery disease is incomplete. Accordingly, factors predicting stroke risk in hypertensive, clinically stable coronary artery disease patients were determined with data from the INternational VErapamil SR-trandolapril STudy (INVEST). Methods The effect of baseline characteristics and on-treatment blood pressure (BP) were analyzed to determine the risk of stroke (fatal or nonfatal) among the 22 576 patients enrolled. Cox proportional-hazards models (unadjusted, adjusted, and time dependent) were used to identify predictors of stroke among subgroups with these characteristics present at entry and on-treatment BP. Results Excellent BP control (at 24 months, >70% <140/90 mm Hg) was achieved during 61 835 patient-years of follow-up, as 377 patients had a stroke (6.1 strokes/1000 patient-years) and 28% of those patients had a fatal stroke. Increased age, black race, US residency, and history of prior myocardial infarction, smoking, stroke/transient ischemic attack, arrhythmia, diabetes, and coronary bypass surgery were associated with an increased risk of stroke. Achieving a systolic BP <140 mm Hg and a diastolic BP <90 mm Hg was associated with a decreased risk of stroke. There was no statistically significant difference in stroke risk comparing the verapamil SR–based with the atenolol-based treatment strategy (adjusted hazard ratio=0.87; 95% CI, 0.71 to 1.06; P=0.17). Conclusions Among hypertensive patients with chronic coronary artery disease, stroke was an important complication associated with significant mortality. Black race, US residency, and conditions associated with increased vascular disease severity and arrhythmia predicted increased stroke risk, whereas achieving a BP <140/90 mm Hg on treatment predicted a reduced stroke risk. PMID:18162623

  7. [Serum angiotensin converting enzyme activity in patients with untreated essential arterial hypertension].

    PubMed

    Huskić, J; Kulenović, H

    1996-01-01

    The serum angiotensin converting enzyme (ACE) in 30 patients with untreated essential arterial hypertension, 30 patients with chronic renal failure accompanied with arterial hypertension and 30 healthy individuals was measured. The subjects of both sexes have been old 35-60 years. The serum ACE activity was determined by the spectrophotometric method, using Hip-Gly-Gly as a substrate. The serum ACE activity significantly increased in patients with arterial hypertension (32.48 +/- 2.02; X +/- SEM) and patients with chronical renal failure accompanied with arterial hypertension (37.10 +/- 1.45) when compared to the healthy individuals (20.83 +/- 1.33). Possible mechanisms of increasing ACE activity with the patients suffering of arterial hypertension are discussed.

  8. [CHANGES OF CAROTID AND VERTEBRAL ARTERIES IN PATENTS WITH ARTERIAL HYPERTENSION AND HEPATOBILIARY PATHOLOGY].

    PubMed

    Polyakov, V Ya; Nikolaev, Yu A; Pegova, S V; Matsievskaya, T R; Obukhov, I V

    2016-01-01

    The study included 1172 patients (410 men and 762 women) at the mean age of 60.3 ± 10.4 years with grade I-II (stage I-II) arterial hypertension (AH) admitted to the clinic of Institute of Experimental Medicine. The patients were divided into 2 groups based on the results of clinical and laboratory diagnostics. Group 1 (n = 525) included patients with AH and hepatobiliary system (HBS) diseases, group 2 (n = 647) patients with AH without HBS diseases. The patients group 1 had a thicker intima-media complex of carotid arteries, higher peak systolic bloodflow rate in the internal and vertebral carotid arteries, more pronounced coiling of internal carotid arteries than patients of group 2. Patients with AH and HBS diseases exhibited correlation between bloodflow rate in external carotid arteries and atherogenicity coefficient. Duplex scanning of neck vessels of in patients with AH without HBS diseases revealed peculiar changes of the intima-media thickness and hemodynamically significant changes of the blood flow in the internal carotid arteries that may be of prognostic value in this nosological syntropy and require the personified approach to diagnostics, treatment, and prevention of these conditions.

  9. [Pediatric pulmonary hypertension and pulmonary arterial hypertension secondary to congenital heart diseases].

    PubMed

    Olguntürk, Rana

    2010-08-01

    Causes of pulmonary arterial hypertension (PAH) are similar in adults and children. The main difference is that PAH secondary to congenital heart diseases, is the predominant cause in pediatric patients. Persistent pulmonary hypertension of the newborn shows completely different clinical course and pathophysiological mechanisms. It is usually seen in full term babies with a high morbidity and mortality rate. Improved prognosis has been reported with inhaled nitric oxide (NO) and extracorporeal membrane oxygenation therapy in babies hospitalized in well equipped and experienced newborn centers. Primary pulmonary hypertension and familial pulmonary hypertension are rare in pediatric age group because the diagnosis is initially made in adolescence. The incidence of PAH secondary to congenital heart disease is estimated as 1.6 - 12.5 case/million/year. Eisenmenger syndrome is diagnosed in 1% of patients with PAH. Patients with left to right shunts are the main group who develop pulmonary vascular disease if not treated in the early infancy. Some cyanotic congenital heart diseases are also the causes of PAH. The best treatment of patients at risk for the development of pulmonary vascular disease is prevention by early surgical elimination of defects or repairing the anatomy. Treatment options with vasodilating agents like NO, prostaglandin analogs, phosphodiesterase -5 inhibitors and endothelin receptor antagonists are used to improve survival and quality of life. Heart lung or bilateral lung transplantation is the only surgical option for many of these patients. Results of national and international registries will bring valuable epidemiological and prognostic perspectives to pediatric PAH.

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

    PubMed

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

    2014-12-01

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

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

    PubMed Central

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

    2014-01-01

    Abstract The age at diagnosis of pulmonary arterial hypertension (PAH) and the prevalence of cardiovascular (CV) risk factors are increasing. We sought to determine whether the response to drug therapy was influenced by CV risk factors in PAH patients. We studied consecutive incident PAH patients (n = 146) between January 1, 2008, and July 15, 2011. Patients were divided into two groups: the PAH–No CV group included patients with no CV risk factors (obesity, systemic hypertension, type 2 diabetes mellitus, permanent atrial fibrillation, mitral and/or aortic valve disease, and coronary artery disease), and the PAH-CV group included patients with at least one. The response to PAH treatment was analyzed in all the patients who received PAH drug therapy. The PAH–No CV group included 43 patients, and the PAH-CV group included 69 patients. Patients in the PAH–No CV group were younger than those in the PAH-CV group (P < 0.0001). In the PAH–No CV group, 16 patients (37%) improved on treatment and 27 (63%) did not improve, compared with 11 (16%) and 58 (84%) in the PAH-CV group, respectively (P = 0.027 after adjustment for age). There was no difference in survival at 30 months (P = 0.218). In conclusion, in addition to older age, CV risk factors may predict a reduced response to PAH drug therapy in patients with PAH. PMID:25610602

  12. The molecular genetics and cellular mechanisms underlying pulmonary arterial hypertension.

    PubMed

    Machado, Rajiv D

    2012-01-01

    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.

  13. Lentil-based diets attenuate hypertension and large-artery remodelling in spontaneously hypertensive rats.

    PubMed

    Hanson, Matthew G; Zahradka, Peter; Taylor, Carla G

    2014-02-01

    Hypertension is a major risk factor for CVD, the leading cause of mortality worldwide. The prevalence of hypertension is expected to continue increasing, and current pharmacological treatments cannot alleviate all the associated problems. Pulse crops have been touted as a general health food and are now being studied for their possible effects on several disease states including hypertension, obesity and diabetes. In the present study, 15-week-old spontaneously hypertensive rats (SHR) were fed diets containing 30% w/w beans, peas, lentils, chickpeas, or mixed pulses or a pulse-free control diet for 4 weeks. Normotensive Wistar-Kyoto (WKY) rats were placed on a control diet. Pulse wave velocity (PWV) was measured weekly, while blood pressure (BP) was measured at baseline and week 4. Fasting serum obtained in week 4 of the study was analysed for circulating lipids. A histological analysis was carried out on aortic sections to determine vascular geometry. Of all the pulse varieties studied, lentils were found to be able to attenuate the rise in BP in the SHR model (P< 0·05). Lentils were able to decrease the media:lumen ratio and media width of the aorta. The total cholesterol (TC), LDL-cholesterol (LDL-C) and HDL-cholesterol levels of rats fed the pulse-based diets were found to be lower when compared with those of the WKY rat and SHR controls (P< 0·05). Although all pulses reduced circulating TC and LDL-C levels in the SHR, only lentils significantly reduced the rise in BP and large-artery remodelling in the SHR, but had no effect on PWV. These results indicate that the effects of lentils on arterial remodelling and BP in the SHR are independent of circulating LDL-C levels.

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

    PubMed Central

    Boueiz, Adel; 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, human immunodeficiency viral infection, portal hypertension, congenital heart disease, and schistosomiasis. Systemic sclerosis (SSc) is an autoimmune multisystem disorder, which affects over 240 persons per million in the United States.[1] Its manifestations are not confined to the skin but may also involve the lungs, kidneys, peripheral circulation, musculoskeletal system, gastrointestinal tract, and heart. The outcome of PAH associated with SSc is worse when compared to other subtypes of PAH. In this review, we summarize available information about the pulmonary vascular and cardiac manifestations of SSc with special emphasis on their prognostic implications as well as the peculiarity of their detection. PMID:25076994

  15. Cardiopulmonary exercise testing in patients with pulmonary arterial hypertension: an evidence-based review.

    PubMed

    Arena, Ross; Lavie, Carl J; Milani, Richard V; Myers, Jonathan; Guazzi, Marco

    2010-02-01

    There is an increasing recognition of the potential value of cardiopulmonary exercise testing (CPX) in patients with pulmonary hypertension (PH). Key CPX characteristics in these patients include: (1) a diminished aerobic capacity; (2) an abnormally elevated minute ventilation-carbon dioxide production relationship; and (3) an abnormally diminished partial pressure of end-tidal carbon dioxide. Given the burgeoning number of original research investigations utilizing CPX in patients with PH, a summation of the presently available body of literature seems timely. A literature search was conducted in pubmed using "cardiopulmonary exercise testing" and "pulmonary arterial hypertension" as key phrases. Only studies conducting exercise testing with simultaneous ventilatory expired gas analysis in subjects with a confirmed diagnosis of pulmonary arterial hypertension were included. Twenty-three investigations were included in this review. Nineteen of the investigations assessed cohorts with resting pulmonary arterial hypertension as the sole diagnosis. Two investigations assessed subjects with chronic obstructive pulmonary disease and pulmonary arterial hypertension: one assessed subjects with pulmonary fibrosis and pulmonary arterial hypertension, and another included groups with exercise-induced pulmonary arterial hypertension and resting pulmonary arterial hypertension. Collectively, these investigations indicate variables obtained from CPX: (1) reflect varying degrees of PH severity; (2) positively respond to several pharmacologic and surgical interventions; and (3) may provide prognostic value. Currently, CPX is not widely utilized in patients with PH. Although more research is required in a number of areas, the present evidence-based review indicates this exercise testing technique may provide valuable information in the PH population.

  16. Add-on therapy with doxazosin in patients with hypertension influences arterial stiffness and albuterol-mediated arterial vasodilation.

    PubMed

    Wykretowicz, Andrzej; Guzik, Przemyslaw; Krauze, Tomasz; Adamska, Karolina; Milewska, Agata; Wysocki, Henryk

    2007-12-01

    Doxazosin is an antihypertensive agent with largely unknown effects on arterial stiffness and vasodilation. The aim of this study was to determine the effect of the addition of doxazosin extended-release (ER) to the standard management of hypertension in patients with inadequately controlled blood pressure (BP) on arterial stiffness and arterial vasodilation. Twenty patients with inadequately controlled hypertension were treated with 4 mg doxazosin ER daily for 16 weeks as an adjunct to their existing antihypertensive regimen. Doxazosin ER add-on therapy was associated with significantly reduced systolic (P < 0.0001) and diastolic (P = 0.0003) BP, improved arterial stiffness (determined by digital volume pulse analysis (P = 0.048) and albuterol-mediated arterial vasodilation (P = 0.030). Add-on therapy with 4 mg of doxazosin ER daily reduces BP and arterial stiffness and improves arterial vasodilation in response to adrenergic stimulation.

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

    PubMed

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

    2013-02-01

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

  18. Versican accumulates in vascular lesions in pulmonary arterial hypertension

    PubMed Central

    Chan, Christina K.; Eriksson, Inger; Johnson, Pamela Y.; Cao, Xiaofang; Westöö, Christian; Norvik, Christian; Andersson-Sjöland, Annika; Westergren-Thorsson, Gunilla; Johansson, Staffan; Hedin, Ulf; Kjellén, Lena; Wight, Thomas N.; Tran-Lundmark, Karin

    2016-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a lethal condition for which there is no effective curative pharmacotherapy. PAH is characterized by vasoconstriction, wall thickening of pulmonary arteries, and increased vascular resistance. Versican is a chondroitin sulfate proteoglycan in the vascular extracellular matrix that accumulates following vascular injury and promotes smooth-muscle cell proliferation in systemic arteries. Here, we investigated whether versican may play a similar role in PAH. Paraffin-embedded lung sections from patients who underwent lung transplantation to treat PAH were used for immunohistochemistry. The etiologies of PAH in the subjects involved in this study were idiopathic PAH, scleroderma, and congenital heart disease (atrial septal defect) with left-to-right shunt. Independent of the underlying etiology, increased versican immunostaining was observed in areas of medial thickening, in neointima, and in plexiform lesions. Western blot of lung tissue lysates confirmed accumulation of versican in patients with PAH. Double staining for versican and CD45 showed only occasional colocalization in neointima of high-grade lesions and plexiform lesions. In vitro, metabolic labeling with [35S]sulfate showed that human pulmonary artery smooth-muscle cells (hPASMCs) produce mainly chondroitin sulfate glycosaminoglycans. In addition, hypoxia, but not cyclic stretch, was demonstrated to increase both versican messenger RNA expression and protein synthesis by hPASMCs. Versican accumulates in vascular lesions of PAH, and the amount of versican correlates more with lesion severity than with underlying etiology or inflammation. Hypoxia is a possible regulator of versican accumulation, which may promote proliferation of pulmonary smooth-muscle cells and vascular remodeling in PAH. PMID:27683612

  19. Galactorrhoea amenorrhoea syndrome due to internal carotid artery aneurysm.

    PubMed Central

    Garg, S. K.; Dash, R. J.

    1985-01-01

    A 32 year old female with hyperprolactinaemia-galactorrhoea-amenorrhoea due to a right internal carotid artery aneurysm just before its bifurcation is described. She had two episodes of subarachnoid haemorrhage necessitating an emergency internal carotid artery ligation. She responded to bromocriptine treatment with restoration of her menses, normalization of circulating prolactin and disappearance of galactorrhoea. Images Figure 1 Figure 2 Figure 3 PMID:4040632

  20. Newly developed hypertension due to juxtaglomerular cell tumor in pregnancy.

    PubMed

    Shin, Yu Seob; Cha, Jai Seong; Kang, Myoung Jae; Park, Jong Kwan; Kim, Hyung Jin; Kim, Myung Ki

    2012-10-01

    An unusual case of juxtaglomerular cell tumor (JCT) is presented. A 29-year-old woman visited our hospital for the management of incidentally detected renal mass due to newly developed hypertension in the 20th week of pregnancy. Laboratory studies showed increased basal plasma renin activity and hypokalemia but serum aldosterone level was normal. Abdominal computed tomography scan showed about 2.4 cm sized multicystic mass in the right kidney. Nephron-sparing surgery was performed with excellent results. On histological examination, the tumor exhibited a structure typical feature of JCT. A few days later the patient's blood pressure had been normalized.

  1. Persistent pulmonary artery hypertension in patients undergoing balloon mitral valvotomy

    PubMed Central

    Nair, Krishna Kumar Mohanan; Pillai, Harikrishnan Sivadasan; Titus, Thomas; Varaparambil, Ajitkumar; Sivasankaran, Sivasubramonian; Krishnamoorthy, Kavassery Mahadevan; Namboodiri, Narayanan; Sasidharan, Bijulal; Thajudeen, Anees; Ganapathy, Sanjay; Tharakan, Jaganmohan

    2013-01-01

    Pulmonary artery pressure (PAP) is known to regress after successful balloon mitral valvotomy (BMV). Data of persistent pulmonary artery hypertension (PPAH) following BMV is scarce. We analyzed the clinical, echocardiographic, and hemodynamic data of 701 consecutive patients who have undergone successful BMV in our institute from 1997 to 2003. Data of 287 patients who had PPAH (defined by pulmonary artery systolic pressure [PASP] of ≥ 40 mmHg at one year following BMV) were compared to the data of 414 patients who did not have PPAH. Patients who had PPAH were older (39.9 ± 9.9 years vs. 29.4 ± 10.1; P < 0.001). They had higher prevalence of atrial fibrillation (AF; 21.9 vs. 12.1%, P < 0.05), moderate or severe pulmonary artery hypertension (PAH) defined as PASP more than 50 mmHg (43.5 vs. 33.8%, P = 0.00), anatomically advanced mitral valve disease as assessed by Wilkin's echocardiographic score > 8 (33.7 vs. 23.2%, P < 0.001), and coexistent aortic valve disease (45.6 vs. 37.9%, P < 0.001) at the baseline. Those patients with PPAH had comparatively lower immediate postprocedural mitral valve area (MVA). On follow-up of more than five years, the occurrence of restenosis (39.3 vs. 10.1%, P = 0.000), new onset heart failure (14% vs. 4%, P < 0.05) and need for reinterventions (9.5% vs. 2.8%, P < 0.05) were higher in the PPAH group. Patients with PPAH were older, sicker, and had advanced rheumatic mitral valve disease. They had higher incidence of restenosis, new onset heart failure, and need for reinterventions on long term follow-up. PPAH represents an advanced stage of rheumatic valve disease and indicates chronicity of the disease, which may be the reason for the poorer prognosis of these patients. Patients with PPAH requires intense and more frequent follow-up. PMID:24015345

  2. Immune and Inflammatory Mechanisms in Pulmonary Arterial Hypertension

    PubMed Central

    El Chami, Hala; Hassoun, Paul M.

    2012-01-01

    Altered immunity and inflammation are increasingly recognized features of pulmonary arterial hypertension (PAH). This is suggested by infiltration of various inflammatory cells (e.g., macrophages, T and B lymphocytes), increased cytokine and growth factor (e.g., VEGF and PDGF) expression in remodeled pulmonary vessels, and the presence of circulating chemokines and cytokines. In certain diseases associated with PAH, increased expression of growth and transcriptional (e.g., Nuclear Factor of Activated T cells or NFAT) factors, and viral protein components (e.g., HIV-1 Nef), appear to contribute directly to recruitment of inflammatory cells in remodeled vessels, and may potentially serve as specific therapeutic targets. This section provides an overview of inflammatory pathways highlighting their potential role in pulmonary vascular remodeling in PAH and the possibility of future targeted therapy. PMID:23009917

  3. The role of endothelin-1 in pulmonary arterial hypertension

    PubMed Central

    Chester, Adrian H.; Yacoub, Magdi H.

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a rare but debilitating disease, which if left untreated rapidly progresses to right ventricular failure and eventually death. In the quest to understand the pathogenesis of this disease differences in the profile, expression and action of vasoactive substances released by the endothelium have been identified in patients with PAH. Of these, endothelin-1 (ET-1) is of particular interest since it is known to be an extremely powerful vasoconstrictor and also involved in vascular remodelling. Identification of ET-1 as a target for pharmacological intervention has lead to the discovery of a number of compounds that can block the receptors via which ET-1 mediates its effects. This review sets out the evidence in support of a role for ET-1 in the onset and progression of the disease and reviews the data from the various clinical trials of ET-1 receptor antagonists for the treatment of PAH. PMID:25405182

  4. Pathogenesis of pulmonary arterial hypertension: lessons from cancer.

    PubMed

    Guignabert, Christophe; Tu, Ly; Le Hiress, Morane; Ricard, Nicolas; Sattler, Caroline; Seferian, Andrei; Huertas, Alice; Humbert, Marc; Montani, David

    2013-12-01

    Although the causal pathomechanisms contributing to remodelling of the pulmonary vascular bed in pulmonary arterial hypertension (PAH) are still unclear, several analogous features with carcinogenesis have led to the emergence of the cancer-like concept. The major similarities concern the altered crosstalk between cells from different tissue types, unexplained proliferation and survival of pulmonary smooth muscle and endothelial cells, the metabolic (glycolytic) shifts, and the association with the immune system. However, major differences between PAH and cancer exist, including the absence of invasion and metastasis, as well as the pathogenic genes involved and the degrees of angiogenesis impairment and genetic instability. It is clear that PAH is not a cancer, but this cancer-like concept has opened a new field of investigation and raises the possibility that antiproliferative and/or oncological drugs may exert therapeutic effects not only in cancer, but also in PAH. Such analogies and differences are discussed here.

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

    PubMed

    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.

  6. [Experience with imatinib to treat pulmonary arterial hypertension].

    PubMed

    García Hernández, Francisco José; Castillo Palma, María Jesús; González León, Rocío; Garrido Rasco, Rocío; Ocaña Medina, Celia; Sánchez Román, Julio

    2008-12-01

    Despite advances in the treatment of patients with pulmonary arterial hypertension (PAH), survival has not improved greatly (is still very affected). Imatinib, an antagonist of platelet-derived growth factor with antiproliferative activity, has been effective in experimental models and clinically in several published reports. We report the results of imatinib therapy in 4 patients with PAH (functional class IV) who were refractory to treatment with drug combinations for this condition. The final outcome was favorable in only 1 of the 4 cases. In this case, the patient was in functional class III and his hemodynamic parameters had improved significantly within 5 months after starting therapy. However, the patient died as a result of severe toxic hepatitis in which imatinib may have played a role. The present report adds to the few already in the literature (4 cases) and suggests that care should continue to be shown when using imatinib to treat PAH.

  7. [Clinical guidelines for detection, prevention, diagnosis and treatment of systemic arterial hypertension in Mexico (2008)].

    PubMed

    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

  8. Prognostic Significance of Biomarkers in Pulmonary Arterial Hypertension

    PubMed Central

    Al-Naamani, Nadine; Palevsky, Harold I.; Lederer, David J.; Horn, Evelyn M.; Mathai, Stephen C.; Roberts, Kari E.; Tracy, Russell P.; Hassoun, Paul M.; Girgis, Reda E.; Shimbo, Daichi; Post, Wendy S.

    2016-01-01

    Rationale: Pulmonary arterial hypertension (PAH) is a rare progressive disease of the pulmonary vasculature that is characterized by endothelial dysfunction, inflammation, and right ventricular dysfunction. Objectives: The main objective was to determine whether endothelial, inflammatory, and cardiac biomarkers would be associated with the World Health Organization functional assessment and survival in patients with PAH. Methods: We performed a retrospective cohort study of patients with PAH enrolled in the Randomized Clinical Trial of Aspirin and Simvastatin for Pulmonary Arterial Hypertension (ASA-STAT). Biomarkers (N-terminal fragment of pro-BNP [NT-pro-BNP], von Willebrand factor [vWF], soluble P selectin, C-reactive protein, total and high-density lipoprotein cholesterol, triglycerides, tumor necrosis factor, IL-6, β-thromboglobulin, and thromboxane B2) were measured at baseline. Patients from the study were followed until lung transplantation, death, or August 1, 2013. Ordinal logistic regression and Cox regression analyses were performed. Measurements and Main Results: Sixty-five patients with PAH were enrolled. The mean age was 51 years, and 86% were women. Higher vWF activity, lower high-density lipoprotein cholesterol, and higher thromboxane B2 levels were associated with worse World Health Organization functional class after adjustment for age, sex, and etiology of PAH. Higher NT-pro-BNP levels, lower vWF activity, and lower total cholesterol were associated with an increased risk of death or lung transplant after adjustment for age, sex, etiology of PAH, and 6-minute-walk distance. Conclusions: In patients with PAH, lower vWF activity and cholesterol levels and higher NT-pro-BNP levels at baseline were associated with an increased risk of death or transplantation. Clinical trial registered with www.clinicaltrials.gov (NCT00384865). PMID:26501464

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

    PubMed

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

    2015-10-01

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

  10. Right ventricular reverse remodelling in Idiopathic Pulmonary Arterial Hypertension diagnosed during pregnancy: Is it possible?

    PubMed

    Paciocco, Giuseppe; Lombi, Andrea; Vincenzi, Antonella; Pesci, Alberto; Achilli, Felice

    2017-01-01

    We present a case of a 36-year-old woman who developed a severe form of Idiopathic Pulmonary Arterial Hypertension (IPAH) during pregnancy and after emergency delivery. The management of IPAH during or after pregnancy is complex. Due to the severity of her IPAH, an upfront triple combination therapy, including i.v. epoprostenol, was started. The rapid institution of this treatment regimen allowed a complete right ventricular reverse remodelling after 1 year of therapy, leading to a down-titration until complete suspension of epoprostenol from the treatment regimen.

  11. Implication of Inflammation and Epigenetic Readers in Coronary Artery Remodeling in Patients With Pulmonary Arterial Hypertension.

    PubMed

    Meloche, Jolyane; Lampron, Marie-Claude; Nadeau, Valérie; Maltais, Mélanie; Potus, François; Lambert, Caroline; Tremblay, Eve; Vitry, Géraldine; Breuils-Bonnet, Sandra; Boucherat, Olivier; Charbonneau, Eric; Provencher, Steeve; Paulin, Roxane; Bonnet, Sébastien

    2017-08-01

    Pulmonary arterial hypertension (PAH) is a vascular disease not restricted to the lungs. Many signaling pathways described in PAH are also of importance in other vascular remodeling diseases, such as coronary artery disease (CAD). Intriguingly, CAD is 4× more prevalent in PAH compared with the global population, suggesting a link between these 2 diseases. Both PAH and CAD are associated with sustained inflammation and smooth muscle cell proliferation/apoptosis imbalance and we demonstrated in PAH that this phenotype is, in part, because of the miR-223/DNA damage/Poly[ADP-ribose] polymerase 1/miR-204 axis activation and subsequent bromodomain protein 4 (BRD4) overexpression. Interestingly, BRD4 is also a trigger for calcification and remodeling processes, both of which are important in CAD. Thus, we hypothesize that BRD4 activation in PAH influences the development of CAD. PAH was associated with significant remodeling of the coronary arteries in both human and experimental models of the disease. As observed in PAH distal pulmonary arteries, coronary arteries of patients with PAH also exhibited increased DNA damage, inflammation, and BRD4 overexpression. In vitro, using human coronary artery smooth muscle cells from PAH, CAD and non-PAH-non-CAD patients, we showed that both PAH and CAD smooth muscle cells exhibited increased proliferation and suppressed apoptosis in a BRD4-dependent manner. In vivo, improvement of PAH by BRD4 inhibitor was associated with a reduction in coronary remodeling and interleukin-6 expression. Overall, this study demonstrates that increased BRD4 expression in coronary arteries of patient with PAH contributes to vascular remodeling and comorbidity development. © 2017 American Heart Association, Inc.

  12. An international physician survey of pulmonary arterial hypertension management

    PubMed Central

    Hinzmann, Barbara; Heinz, Sabina; Gall, Henning; Jenkins, David; Kim, Nick H.; Lang, Irene

    2016-01-01

    Abstract We conducted an international study to evaluate practices in the diagnosis and management of pulmonary arterial hypertension (PAH) globally across different geographic regions. Between July and October 2012, PAH-treating physicians completed a 15-minute online questionnaire and provided patient record data for their 3 or 5 most recent patients with PAH. Overall, 560 physicians (Europe: 278; United States: 160; Argentina: 53; Japan: 69) completed the questionnaire and provided data for 2,618 patients. The proportion of physicians who described themselves as working in or affiliated with a specialized pulmonary hypertension center ranged from 13% in Argentina to 74% in the United States. At the time of diagnosis, patients’ New York Heart Association functional class differed significantly between regions. At the time of last assessment, functional class had improved overall, and differences between regions had largely disappeared. A large proportion of patients did not undergo right heart catheterization for the diagnosis of PAH (Europe: 7%–21%; United States: 21%; Japan: 19%; Argentina: 51%). Variations in management included greater use of phosphodiesterase 5 inhibitors in the United States than in Europe and Japan and greater use of triple or greater combination therapy in Japan than in other regions. Results from this study, which includes a global aspect of PAH care, demonstrate that there are significant differences in PAH management between regions and low adherence to guidelines recommending right heart catheterization for the diagnosis of PAH. PMID:27683611

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

    PubMed Central

    Gabbay, Eli; Fraser, John; McNeil, Keith

    2007-01-01

    The dual endothelin receptor antagonist, bosentan, is an orally active therapy, which is effective in the treatment of pulmonary arterial hypertension (PAH). This review critically appraises the evidence for the efficacy of bosentan in idiopathic and familial PAH, in PAH associated with connective tissue disease and in PAH which may develop in association with other conditions. Data from the pivotal placebo controlled studies and their open labeled extensions as well as long term survival and quality of life data is presented. Data is also presented on the potential benefit of bosentan in patients with inoperable chronic thromboembolic pulmonary hypertension. The safety and tolerability of bosentan as well as drug interactions are discussed. Dosage recommendations in adults and pediatrics are presented. An algorithm is provided to guide the reader in monitoring potential increases in alanine and aspartate transaminase levels that may occur with bosentan use and the dose adjustments that are recommended as a result of any increase in the levels of these enzymes are shown. Finally, the role of bosentan as part of combination therapy in PAH is examined. PMID:18200808

  14. Predicting survival in pulmonary arterial hypertension in the UK.

    PubMed

    Lee, Wai-Ting Nicola; Ling, Yi; Sheares, Karen K; Pepke-Zaba, Joanna; Peacock, Andrew John; Johnson, Martin Keith

    2012-09-01

    Contemporary prognostic equations in pulmonary arterial hypertension (PAH) derived from US and French cohorts may not perform as well in the UK as a locally derived scoring scheme. The aim of the study was to develop and validate a UK risk score to predict prognosis in PAH. Baseline mortality predictors identified by multivariate Cox analysis in 182 incident PAH patients were used to derive the Scottish composite score (SCS). Its prognostic performance in an independent UK cohort was compared with the French registry and Pulmonary Hypertension Connection (PHC) registry equations using Brier scores (BS). The SCS based on age, sex, aetiology, right atrial pressure, cardiac output and 6-min walk distance predicted survival in the validation cohort (hazard ratio (HR) 1.7 per point increase; p<0.001) and provided further prognostic stratification in World Health Organization (WHO) functional class III patients (HR 1.8 per point increase; p<0.001). It was more accurate than the French registry equation in predicting 1-yr survival (BS: 0.092 versus 0.146; p=0.001) and 2-yr survival (0.131 versus 0.255; p<0.001). There was no significant difference in BS between the SCS and PHC registry equation. The SCS predicts survival and can be used to supplement WHO functional class in prognostication.

  15. [Arterial hypertension in immigrant patients in Spanish primary health care].

    PubMed

    Llisterri Caro, José Luis; Alonso Moreno, Francisco J; Martincano Gómez, José Luis; López Abuin, José Manuel; Rodríguez Roca, Gustavo C; Banegas Banegas, José R

    2007-07-07

    To evaluate the arterial hypertension (AHT) prevalence in a wide sample of immigrant patients. A transversal and multicentric study that has included immigrant patients aged 18 years or more, consecutive sampling recruitment in primary healthcare consultations. The patient was defined with AHT hypertension when the average of 6 measurements in 3 visits (2 measurements per visit) was > or = 140 mmHg for the systolic blood pressure and/or 90 mmHg for diastolic blood pressure or if the patient had been previously diagnosed. 1,424 immigrants were followed-up (53.1% women) with average age (standard deviation) of 42.8 (13.1) years and mean stay in our country of 5.6 (5.7) years. Most of the patients' origin was Central and South America (40.2%) and Eastern Europe (21.9%). The prevalence of AHT was 31.4% (95% confidence interval [CI], 30.1-32.7%), of which the 62.1% where known patients. Patients coming from Asia showed a significant higher prevalence of AHT (40.0%; 95% CI, 38.7-41.3). Three of each 10 immigrant patients have AHT. There are significant differences according to the gender, the origin and period of residence of these patients.

  16. Pulmonary arterial hypertension and portal hypertension in a patient with hereditary hemorrhagic telangiectasia.

    PubMed

    Pousada, Guillermo; Baloira, Adolfo; Valverde, Diana

    2015-03-15

    Pulmonary arterial hypertension (PAH) is a rare disease that could be inherited with an autosomal dominant pattern. Mutations in BMPR2 gene are described in over 70% of cases, although other genes are involved in lesser extend in PAH. Hereditary hemorrhagic telangiectasia (HHT) is another rare autosomal dominant disease. PAH is a rare complication of HHT that occurs in less than 1% of cases. Liver cirrhosis with portal hypertension is also associated with the presence of PAHs in 1-2% of cases. We present here a patient with HHT who developed PAH shortly after showing portal hypertension. Some genes (BMPR2, ACVRL1, ENG) seem to play an important role in PAH pathogenesis. We analyzed these genes, detecting mutations in BMPR2 gene (c.1021G>A (V341L), c.327G>A (p.Q109Q)), ACVRL1 (c.313+20C>A, c.1502+7A>G) and ENG (c.498G>A (Q166Q)). The patient also had 3 polymorphisms in the TRPC6 gene (c.1-361A>T, c.1-254C>G, c.1-218C>T). The study of these genes will help us to identify and track individuals susceptible for developing PAH associated with other diseases. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

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

    PubMed

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

    2016-04-10

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

  18. Non-invasive measurements of arterial compliance in hypertensive compared with normotensive adults.

    PubMed

    Roman, M J; Pini, R; Pickering, T G; Devereux, R B

    1992-08-01

    To determine differences in arterial compliance attributable to hypertension. Since measurements of arterial compliance have tended to vary in the past according to the method used, a new technique comprising carotid ultrasound and simultaneous, calibrated, carotid pressure waveform measurements was tested in 43 hypertensives and 43 control subjects matched for age, gender and body size. There was a significant reduction in compliance among the hypertensive patients, as estimated by the elastic modulus and the ratio of stroke volume to pulse pressure. However, when the non-linearity of the pressure-volume relationship and the impact of distending pressure were taken into account, by the arterial stiffness index and by the increase in arterial wall thickness associated with hypertension by Young's modulus, there were no significant differences in arterial compliance between the two groups.

  19. Complex inheritance in Pulmonary Arterial Hypertension patients with several mutations

    PubMed Central

    Pousada, Guillermo; Baloira, Adolfo; Valverde, Diana

    2016-01-01

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

  20. Signal transduction in the development of pulmonary arterial hypertension

    PubMed Central

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

    2013-01-01

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

  1. Signal transduction in the development of pulmonary arterial hypertension.

    PubMed

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

    2013-04-01

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

  2. Peripheral airways obstruction in idiopathic pulmonary artery hypertension (primary).

    PubMed

    Fernandez-Bonetti, P; Lupi-Herrera, E; Martinez-Guerra, M L; Barrios, R; Seoane, M; Sandoval, J

    1983-05-01

    The mechanical properties of the lung were studied in ten nonsmokers with idiopathic pulmonary artery hypertension (IPAH) (mean pulmonary artery pressure 65.7 +/- 30 mm Hg). In the routine lung test, residual volume was found to be abnormal (greater than 120 percent of the predicted) in seven patients, and measured airway resistance was normal in eight out of the ten patients. A decreased FEF 75-85 percent, abnormal values for the helium-air flow ratios and increased closing capacities were documented in eight of ten patients in whom lung elastic recoil was normal (six of ten) or increased (four of ten). These features suggest peripheral airways obstruction (PAO) which was also supported by histopathologic findings in three cases (one biopsy and two necropsies). The observed changes in lung compliance could be related to the behavior of the coupling of the air-space and vascular compartments. The etiology of PAO in IPAH patients is not known, but our results indicate that both the peripheral airways and the pulmonary circulation are affected. The knowledge of PAO in IPAH patients could help to better understand the observed V/Q inequality in this entity.

  3. LTB4 activates pulmonary artery adventitial fibroblasts in pulmonary hypertension

    PubMed Central

    Jiang, Xinguo; Tamosiuniene, Rasa; Sung, Yon K.; Shuffle, Eric M.; Tu, Allen B.; Valenzuela, Antonia; Jiang, Shirley; Zamanian, Roham T.; Fiorentino, David F.; Voelkel, Norbert F.; Peters-Golden, Marc; Stenmark, Kurt R.; Chung, Lorinda; Rabinovitch, Marlene; Nicolls, Mark R.

    2015-01-01

    A recent study demonstrated a significant role for leukotriene B4 (LTB4) causing pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). LTB4 was found to directly injure luminal endothelial cells and promote growth of the smooth muscle cell layer of pulmonary arterioles. The purpose of the current study was to determine the effects of LTB4 on the pulmonary adventitial layer, largely composed of fibroblasts. Here, we demonstrate that LTB4 enhanced human pulmonary artery adventitial fibroblast (HPAAF) proliferation, migration and differentiation in a dose-dependent manner through its cognate G-protein coupled receptor, BLT1. LTB4 activated HPAAF by up-regulating p38 MAPK as well as Nox4 signaling pathways. In an autoimmune model of PH, inhibition of these pathways blocked perivascular inflammation, decreased Nox4 expression, reduced reactive oxygen species production, reversed arteriolar adventitial fibroblast activation and attenuated PH development. This study uncovers a novel mechanism by which LTB4 further promotes PAH pathogenesis, beyond its established effects on endothelial and smooth muscle cells, by activating adventitial fibroblasts. PMID:26558820

  4. Inhalation of Stachybotrys chartarum causes pulmonary arterial hypertension in mice

    PubMed Central

    Ochiai, Eri; Kamei, Katsuhiko; Watanabe, Akira; Nagayoshi, Masaru; Tada, Yuji; Nagaoka, Tetsutaro; Sato, Koichi; Sato, Ayaka; Shibuya, Kazutoshi

    2008-01-01

    Inhalation of Stachybotrys chartarum, a ubiquitous fungus in our living environment, has been suspected as a cause of acute idiopathic pulmonary haemorrhage in infants, but its relation to human diseases is not yet known. The aim of present study was to investigate the effect of repeated intratracheal injection of the fungus into mice, paying special attention to the pulmonary vascular system. Spores of S. chartarum were injected into the trachea of mice from 6 to 18 times over 4–12 weeks, and the lungs were examined by histopathology, morphometrics and haemodynamics. When 1 × 104 spores/mouse were injected, histopathological examination showed the development of pulmonary arterial hypertension (PAH). Symmetrical thickening of the intima and media of the pulmonary arterial walls was seen after six injections over 4 weeks. Right ventricular hypertrophy was also evident after 12 injections. PAH was confirmed by the elevation of right ventricular systolic pressure (20.1 ± 5.7 mmHg in the injected group vs. 12.0 ± 2.4 mmHg in the control group, P < 0.01). This study showed that the inhalation of S. chartarum caused PAH in mice, suggesting a potential of S. chartarum as a cause of human health problem such as PAH. PMID:18460072

  5. Inhalation of Stachybotrys chartarum causes pulmonary arterial hypertension in mice.

    PubMed

    Ochiai, Eri; Kamei, Katsuhiko; Watanabe, Akira; Nagayoshi, Masaru; Tada, Yuji; Nagaoka, Tetsutaro; Sato, Koichi; Sato, Ayaka; Shibuya, Kazutoshi

    2008-06-01

    Inhalation of Stachybotrys chartarum, a ubiquitous fungus in our living environment, has been suspected as a cause of acute idiopathic pulmonary haemorrhage in infants, but its relation to human diseases is not yet known. The aim of present study was to investigate the effect of repeated intratracheal injection of the fungus into mice, paying special attention to the pulmonary vascular system. Spores of S. chartarum were injected into the trachea of mice from 6 to 18 times over 4-12 weeks, and the lungs were examined by histopathology, morphometrics and haemodynamics. When 1 x 10(4) spores/mouse were injected, histopathological examination showed the development of pulmonary arterial hypertension (PAH). Symmetrical thickening of the intima and media of the pulmonary arterial walls was seen after six injections over 4 weeks. Right ventricular hypertrophy was also evident after 12 injections. PAH was confirmed by the elevation of right ventricular systolic pressure (20.1 +/- 5.7 mmHg in the injected group vs. 12.0 +/- 2.4 mmHg in the control group, P < 0.01). This study showed that the inhalation of S. chartarum caused PAH in mice, suggesting a potential of S. chartarum as a cause of human health problem such as PAH.

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

    PubMed

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

    2015-07-01

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

  7. Aerobic, resistance and combined exercise training on arterial stiffness in normotensive and hypertensive adults: A review.

    PubMed

    Li, Yanlei; Hanssen, Henner; Cordes, Mareike; Rossmeissl, Anja; Endes, Simon; Schmidt-Trucksäss, Arno

    2015-01-01

    Exercise training has different effects on arterial stiffness according to training modalities. The optimal exercise modality for improvement of arterial function in normotensive and hypertensive individuals has not been well established. In this review, we aim to evaluate the effects of aerobic, resistance and combined aerobic and resistance training on arterial stiffness in individuals with and without hypertension. We systematically searched the Pubmed and Web of Science database from 1985 until December 2013 for relevant randomised controlled trials (RCTs). The data were extracted by one investigator and checked by a second investigator. The training effects on arterial stiffness were estimated using weighted mean differences of the relative changes (%) with 95% confidence intervals (CIs). We finally reviewed the results from 17 RCTs. The available evidence indicates that aerobic exercise tends to have a beneficial effect on arterial stiffness in normotensive and hypertensive patients, but does not affect arterial stiffness in patients with isolated systolic hypertension. Resistance exercise has differing effects on arterial stiffness depending on type and intensity. Vigorous resistance training is associated with an increase in arterial stiffness. There seem to be no unfavourable effects on arterial stiffness if the training is of low intensity, in a slow eccentric manner or with lower limb in healthy individuals. Combined training has neutral or even a beneficial effect on arterial stiffness. In conclusion, our review shows that exercise training has varying effects on arterial stiffness depending on the exercise modalities.

  8. Endothelial GATA-6 deficiency promotes pulmonary arterial hypertension.

    PubMed

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

    2013-06-01

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

  9. Role for DNA damage signaling in pulmonary arterial hypertension.

    PubMed

    Meloche, Jolyane; Pflieger, Aude; Vaillancourt, Mylène; Paulin, Roxane; Potus, François; Zervopoulos, Sotirios; Graydon, Colin; Courboulin, Audrey; Breuils-Bonnet, Sandra; Tremblay, Eve; Couture, Christian; Michelakis, Evangelos D; Provencher, Steeve; Bonnet, Sébastien

    2014-02-18

    Pulmonary arterial hypertension (PAH) is associated with sustained inflammation known to promote DNA damage. Despite these unfavorable environmental conditions, PAH pulmonary arterial smooth muscle cells (PASMCs) exhibit, in contrast to healthy PASMCs, a pro-proliferative and anti-apoptotic phenotype, sustained in time by the activation of miR-204, nuclear factor of activated T cells, and hypoxia-inducible factor 1-α. We hypothesized that PAH-PASMCs have increased the activation of poly(ADP-ribose) polymerase-1 (PARP-1), a critical enzyme implicated in DNA repair, allowing proliferation despite the presence of DNA-damaging insults, eventually leading to PAH. Human PAH distal pulmonary arteries and cultured PAH-PASMCs exhibit increased DNA damage markers (53BP1 and γ-H2AX) and an overexpression of PARP-1 (immunoblot and activity assay), in comparison with healthy tissues/cells. Healthy PASMCs treated with a clinically relevant dose of tumor necrosis factor-α harbored a similar phenotype, suggesting that inflammation induces DNA damage and PARP-1 activation in PAH. We also showed that PARP-1 activation accounts for miR-204 downregulation (quantitative reverse transcription polymerase chain reaction) and the subsequent activation of the transcription factors nuclear factor of activated T cells and hypoxia-inducible factor 1-α in PAH-PASMCs, previously shown to be critical for PAH in several models. These effects resulted in PASMC proliferation (Ki67, proliferating cell nuclear antigen, and WST1 assays) and resistance to apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling and Annexin V assays). In vivo, the clinically available PARP inhibitor ABT-888 reversed PAH in 2 experimental rat models (Sugen/hypoxia and monocrotaline). These results show for the first time that the DNA damage/PARP-1 signaling pathway is important for PAH development and provide a new therapeutic target for this deadly disease with high translational potential.

  10. Pulmonary arterial hypertension in critically ill elderly patients

    PubMed Central

    Zhang, Yun-yun; Xu, Fan; Chu, Ming; Bi, Li-qing

    2017-01-01

    Objective: To assess the incidence, possible risk factors and prognosis of pulmonary arterial hypertension (PAH) in critically ill elderly patients. Methods: We selected 122 cases admitted to the ICU, ages 60–93 years old. An echocardiography examination was performed within four days after admission to the ICU. PAH is usually suspected if the patient’s pulmonary artery systolic pressure ≥ 40 mmHg. We collected echocardiography data, relevant clinical data and routine laboratory data; we then used a statistical method to analyze the risk factors for PAH in critically ill elderly patients and examined its impact on the prognosis. Results: Total 51 patients were diagnosed with PAH. The prevalence of critically ill elderly patients with PAH was 41.8%. The ANOVA analysis showed that if patients had COPD (P = 0.031) and/or respiratory failure (P = 0.021), they were more prone to PAH. An enlarged left atrium (P = 0.038) and/or right ventricle (P = 0.029), a declining left ventricle fractional shortening rate (P = 0.038), and an elevated amount of the brain natriuretic peptides (P = 0.046) were all associated with the occurrence of PAH. Multivariate regression analysis showed that the left atrial diameter (P = 0.045) was the risk factor in critically ill elderly patients with PAH. The 30-day mortality rate was 33.3% for elderly patients with PAH, which is statistically significant (P = 0.035) when compared with the mortality rate of patients with normal pulmonary artery pressure. Our multivariate regression analysis also showed that, for critically ill elderly patients admitted in the ICU, PAH (P = 0.039) is risk factor for increased mortality. Conclusions: A higher incidence of PAH occurs in critically ill elderly patients. PAH is more likely to occur in patients with an enlarged left atrium, and these problems adversely impact the prognosis. PMID:28367167

  11. Incidence of pleural effusions in idiopathic and familial pulmonary arterial hypertension patients.

    PubMed

    Tang, Ke-Jing; Robbins, Ivan M; Light, Richard W

    2009-09-01

    Pleural effusion occurs often in patients with left heart failure. There are no large-scale clinical studies investigating the incidence of pleural effusion in patients with right heart failure (RHF) alone. To determine the incidence of pleural effusions in patients with idiopathic pulmonary arterial hypertension (IPAH) and familial pulmonary arterial hypertension (FPAH). Consecutive IPAH and FPAH patients who were treated at Vanderbilt University Medical Center were retrospectively studied. Pleural effusions were detected by chest radiograph, chest CT scan, ultrasound, or autopsy. Thirty-one of 147 patients (21.1%) with IPAH (128 patients) or FPAH (19 patients) had pleural effusions. Ten patients had explanations for the pleural effusions other than RHF. Two patients had no obvious explanations. The remaining 19 patients had RHF. When compared with the patients without pleural effusions, the patients with pleural effusions due to RHF had significantly higher mean right atrial pressure (16.0 +/- 6.8 vs 8.8 +/- 5.5 mm Hg, respectively; p < 0.001). There was no significant difference in other hemodynamic parameters between the two patient groups. The majority of effusions due to RHF are trace to small (63.2%) and right sided (57.9%) or bilateral (26.3%). Of the 19 patients with pleural effusions due to RHF, 8 patients had ascites, and 1 patient had moderate pericardial effusion. Four of the five patients who underwent thoracentesis had transudates. Our study in IPAH and FPAH patients demonstrates that pleural effusions frequently occur in patients with isolated RHF.

  12. Central Artery Stiffness in Hypertension and Aging: A Problem with Cause and Consequence

    PubMed Central

    Humphrey, Jay D.; Harrison, David G.; Figueroa, C. Alberto; Lacolley, Patrick; Laurent, Stéphane

    2015-01-01

    Systemic hypertension is a risk factor for many diseases affecting the heart, brain, and kidneys. It has long been thought that hypertension leads to a thickening and stiffening of central arteries (i.e., stiffness is a consequence) while more recent evidence suggests that stiffening precedes hypertension (i.e., stiffness is a cause). We submit, however, that consideration of the wall biomechanics and hemodynamics reveals an insidious positive feedback loop that may render it irrelevant whether hypertension causes or is caused by central arterial stiffening. A progressive worsening can ensue in either case, thus any onset of stiffening merits early intervention. PMID:26846637

  13. Wave reflection correlates with pulmonary vascular wall thickening in rats with pulmonary arterial hypertension.

    PubMed

    Fukumitsu, Masafumi; Kawada, Toru; Shimizu, Shuji; Turner, Michael J; Uemura, Kazunori; Sugimachi, Masaru

    2017-09-14

    Wave reflection is enhanced in patients with pulmonary arterial hypertension (PAH), which may be derived from a mismatch of pulmonary artery (PA) impedance between proximal and distal sites of arteries. Whether enhanced wave reflection correlates with histological remodeling remains unknown, partly because lung biopsy is not clinically recommended for PAH patients due to substantial risks of mortality and morbidity. Pulmonary hypertension was induced by SU5416 injection and 3-week hypoxic exposure (SuHx-PH) in rats, and hemodynamic and histological examinations were performed at 4weeks (SuHx-PH4W) and 8weeks (SuHx-PH8W) after SU5416 injection (n=7 each). Two groups of age-matched normal rats were also analyzed (n=7 each). Using an elastic tube with a 3-element Windkessel model, PA impedance was parameterized as pulmonary artery compliance (CP), peripheral resistance (RP), characteristic impedance (ZC), and transmission time (TD) in conducting arteries. Wave reflection was quantified as reflection gain at 0 Hz (Γgain) in the frequency domain, and as the ratio of peak backward pressure to peak forward pressure (KB/F) in the time domain. The SuHx-PH groups demonstrated increased RP and ZC, and decreased CP and TD compared with normal groups. Γgain and KB/F were significantly higher in the SuHx-PH8W group than in the SuHx-PH4W group, and correlated strongly with a histological index of vascular wall thickening (R(2)=0.839, P<0.001 for Γgain and R(2)=0.775, P<0.001 for KB/F). Enhanced wave reflection caused by abnormal PA impedance correlates with histological remodeling, and may have a diagnostic value in clinical staging of PAH. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  14. Severe arterial hypertension: a possible complication of McCune-Albright syndrome.

    PubMed

    Ohata, Yasuhisa; Yamamoto, Takehisa; Mori, Ikuko; Kikuchi, Toru; Michigami, Toshimi; Imanishi, Yasuo; Satomura, Kenichi; Ida, Shinobu; Ozono, Keiichi

    2009-07-01

    McCune-Albright syndrome is characterized by café-au-lait spot, multiple endocrine hyperfunction, and polyostotic fibrous dysplasia. A somatic point mutation of Gsalpha protein leads to an increase in the Gsalpha-associated hormone activity in McCune-Albright syndrome. Because cyclic adenosine 3',5'-monophosphate stimulates the dopamine beta hydroxylase gene, an activating mutation of the Gsalpha protein may cause the hyperproduction of norepinephrine via dopamine. We report on a 9-year-old girl with McCune-Albright syndrome complicated by severe arterial hypertension. The urinary excretion of norepinephrine was 5- to 10-fold higher than in age-matched controls. Meta-iodobenzylguanidine scintigraphy and positron emission tomography/computed tomography (PET/CT) revealed no hot spots. These findings suggest that severe hypertension might be due to an activating mutation of Gsalpha protein in sympathetic ganglia. Because of the reported association of GNAS1 gene polymorphism with hypertension, our patient provides further evidence for a role of Gsalpha protein in hypertension.

  15. Licorice-induced hypertension: a case of pseudohyperaldosteronism due to jelly bean ingestion.

    PubMed

    Foster, Christopher A; Church, Kristen S; Poddar, Megha; Van Uum, Stan H M; Spaic, Tamara

    2017-04-01

    Hypertension is one of the most common problems encountered in the primary care setting. Numerous secondary causes of hypertension exist and are potentially reversible. The ability to screen for such causes and manage them effectively may spare patients from prolonged medical therapy and hypertensive complications. Licorice can cause hypertension and hypokalemia due its effects on cortisol metabolism. We report a case of jelly bean ingestion that highlights the presentation, pathophysiology and management of licorice-induced hypertension.

  16. The impact of occupational stress factors on temporary work disability related to arterial hypertension and its complications.

    PubMed

    Lazaridis, Konstantinos; Jovanović, Jovica; Jovanović, Jovana; Šarac, Ivana; Jovanović, Stefan

    2017-06-01

    To determine which specific groups of occupational stress factors influence the duration of temporary work disability related to arterial hypertension and joint complications/co-morbidities. Workers (n = 1398; 1009 in the exposed group, 389 in the control group) with arterial hypertension who worked at one workplace for a minimum of 10 years were divided into 10 subgroups, depending on the presence of joint complications/co-morbidities. The intensity of seven groups of occupational stress factors, the total score of Occupational Stress Index (OSI) and the average number of lost working days during 1 year were analysed. The number of lost working days due to arterial hypertension and joint complications/co-morbidities was significantly higher in the exposed group. In all subgroups of the exposed group there was a high correlation between the number of lost working days and the total OSI score. Specific occupational stress factors were associated with specific complications: High Demands with chronic myocardial infarction, Strictness with cerebral haemorrhage, Conflict/Uncertainty with cerebral infarction, Extrinsic Time Pressure with acute myocardial infarction, and Avoidance/Symbolic Aversiveness with non-insulin-dependent diabetes. There are specific groups of occupational stress factors which can influence the duration of work disability associated with certain complications and co-morbidities of arterial hypertension.

  17. Cigarette smoking and hypertension. Factors independently associated with blood hyperviscosity and arterial rigidity.

    PubMed

    Levenson, J; Simon, A C; Cambien, F A; Beretti, C

    1987-01-01

    The effects of cigarette smoking and hypertension on hemorheological variables (blood viscosity over a wide range of shear rates, plasma viscosity, microhematocrit, and plasma protein concentration) and on arterial stiffness (pulse wave velocity) were investigated in 33 normotensive men and 81 mild to moderately hypertensive men. Of these, 22 normotensive and 24 hypertensive subjects were cigarette smokers. Cigarette smoking and hypertension were independently associated with higher blood viscosity at all studied shear rates (from 0.2 to 241 sec-1) as well as with higher plasma viscosity, hematocrit, and pulse wave velocity. At constant hematocrit levels, hypertension remained associated with a higher blood viscosity, while the association with cigarette smoking disappeared. Normotensive smokers had the same increase of blood and plasma viscosity and pulse wave velocity as hypertensive nonsmokers. No interactive effects of hypertension or cigarette smoking on blood or arterial variables were observed, suggesting that the effect of these two factors on blood and vascular rheology are cumulative. Smoking and hypertension may change the flow properties of the blood and the behavior of the arterial wall and this may explain the arterial damage observed in cigarette smokers and hypertensive patients.

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

    PubMed

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

    2014-06-01

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

  19. Add-on therapy with doxazosin in patients with hypertension influences arterial stiffness and albuterol-mediated arterial vasodilation

    PubMed Central

    Wykretowicz, Andrzej; Guzik, Przemyslaw; Krauze, Tomasz; Adamska, Karolina; Milewska, Agata; Wysocki, Henryk

    2007-01-01

    What is already known about this subject Hypertension is associated with increased arterial stiffness and impaired endothelial function. Arterial vasodilation depends on endothelial function and can be regulated by β2-adrenergic stimulation. Doxazosin is a known and potent antihypertensive agent. However, its effects on arterial stiffness and vasodilation have not been fully established. What this study adds Sixteen-week add-on antihypertensive therapy with 4 mg of doxazosin extended release daily: Reduces arterial stiffness. Improves albuterol-mediated, i.e. endothelium-dependent, arterial vasodilation. Does not influence nitroglycerin-mediated, i.e. endothelium-independent, arterial vasodilation. Aims Doxazosin is an antihypertensive agent with largely unknown effects on arterial stiffness and vasodilation. The aim of this study was to determine the effect of the addition of doxazosin extended-release (ER) to the standard management of hypertension in patients with inadequately controlled blood pressure (BP) on arterial stiffness and arterial vasodilation. Methods Twenty patients with inadequately controlled hypertension were treated with 4 mg doxazosin ER daily for 16 weeks as an adjunct to their existing antihypertensive regimen. Results Doxazosin ER add-on therapy was associated with significantly reduced systolic (P < 0.0001) and diastolic (P = 0.0003) BP, improved arterial stiffness (determined by digital volume pulse analysis (P = 0.048) and albuterol-mediated arterial vasodilation (P = 0.030). Conclusions Add-on therapy with 4 mg of doxazosin ER daily reduces BP and arterial stiffness and improves arterial vasodilation in response to adrenergic stimulation. PMID:17635498

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

    PubMed

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

    2012-01-01

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

  1. Inhibition of Excessive Cell Proliferation by Calcilytics in Idiopathic Pulmonary Arterial Hypertension

    PubMed Central

    Yamamura, Aya; Ohara, Naoki; Tsukamoto, Kikuo

    2015-01-01

    Idiopathic pulmonary arterial hypertension (IPAH) is a rare and progressive disease of unknown pathogenesis. Vascular remodeling due to excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) is a critical pathogenic event that leads to early morbidity and mortality. The excessive cell proliferation is closely linked to the augmented Ca2+ signaling in PASMCs. More recently, we have shown by an siRNA knockdown method that the Ca2+-sensing receptor (CaSR) is upregulated in PASMCs from IPAH patients, involved in the enhanced Ca2+ response and subsequent excessive cell proliferation. In this study, we examined whether pharmacological blockade of CaSR attenuated the excessive proliferation of PASMCs from IPAH patients by MTT assay. The proliferation rate of PASMCs from IPAH patients was much higher (~1.5-fold) than that of PASMCs from normal subjects and patients with chronic thromboembolic pulmonary hypertension (CTEPH). Treatment with NPS2143, an antagonist of CaSR or calcilytic, clearly suppressed the cell proliferation in a concentration-dependent manner (IC50 = 2.64 μM) in IPAH-PASMCs, but not in normal and CTEPH PASMCs. Another calcilytic, Calhex 231, which is structurally unrelated to NPS2143, also concentration-dependently inhibited the excessive proliferation of IPAH-PASMCs (IC50 = 1.89 μM). In contrast, R568, an activator of CaSR or calcimimetic, significantly facilitated the proliferation of IPAH-PASMCs (EC50 = 0.33 μM). Similar results were obtained by BrdU incorporation assay. These results reveal that the excessive PASMC proliferation was modulated by pharmacological tools of CaSR, showing us that calcilytics are useful for a novel therapeutic approach for pulmonary arterial hypertension. PMID:26375676

  2. Endothelin-1 Pathway Polymorphisms and Outcomes in Pulmonary Arterial Hypertension

    PubMed Central

    Gomberg-Maitland, Mardi; Demarco, Teresa; Frost, Adaani E.; Torbicki, Adam; Langleben, David; Pulido, Tomas; Correa-Jaque, Priscilla; Passineau, Michael J.; Wiener, Howard W.; Tamari, Mayumi; Hirota, Tomomitsu; Kubo, Michiaki; Tiwari, Hemant K.

    2015-01-01

    Rationale: Pulmonary arterial hypertension (PAH) is a progressive fatal disease. Variable response and tolerability to PAH therapeutics suggests that genetic differences may influence outcomes. The endothelin pathway is central to pulmonary vascular function, and several polymorphisms and/or mutations in the genes coding for endothelin (ET)-1 and its receptors correlate with the clinical manifestations of other diseases. Objectives: To examine the interaction of ET-1 pathway polymorphisms and treatment responses of patients with PAH treated with ET receptor antagonists (ERAs). Methods: A total of 1,198 patients with PAH were prospectively enrolled from 45 U.S. and Canadian pulmonary hypertension centers or retrospectively from global sites participating in the STRIDE (Sitaxsentan To Relieve Impaired Exercise) trials. Comprehensive objective measures including a 6-minute-walk test, Borg dyspnea score, functional class, and laboratory studies were completed at baseline, before the initiation of ERAs, and repeated serially. Single-nucleotide polymorphisms from ET-1 pathway candidate genes were selected from a completed genome-wide association study performed on the study cohort. Measurements and Main Results: Patient efficacy outcomes were analyzed for a relationship between ET-1 pathway polymorphisms and clinical efficacy using predefined, composite positive and negative outcome measures in 715 European descent samples. A single-nucleotide polymorphism (rs11157866) in the G-protein alpha and gamma subunits gene was significantly associated, accounting for multiple testing, with a combined improvement in functional class and 6-minute-walk distance at 12 and 18 months and marginally significant at 24 months. Conclusions: ET-1 pathway associated polymorphisms may influence the clinical efficacy of ERA therapy for PAH. Further prospective studies are needed. PMID:26252367

  3. Left ventricular dysfunction in patients with suspected pulmonary arterial hypertension*

    PubMed Central

    Gavilanes, Francisca; Jr, José Leonidas Alves; Fernandes, Caio; Prada, Luis Felipe Lopes; Jardim, Carlos Viana Poyares; Morinaga, Luciana Tamie Kato; Dias, Bruno Arantes; Hoette, Susana; Souza, Rogerio

    2014-01-01

    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. PMID:25610501

  4. Which prognostic factors should be used in pulmonary arterial hypertension in elderly patients?

    PubMed Central

    Akdeniz, Bahri; Ozpelit, Ebru

    2017-01-01

    In recent times, the prevalence of pulmonary arterial hypertension (PAH) is more commonly seen among elderly populations. The increased prevalence of hypertension, diabetes, obesity, arterial stiffness, as well as diastolic dysfunction, may cause endothelial dysfunction and affect pulmonary vasculature. Furthermore, older patients have certain differences in clinical characteristics and outcomes. In this article, the special characteristics of aging in PAH patients have been reviewed, while the risk predictors of elderly patients are also discussed. PMID:28270839

  5. Mutations of NOTCH3 in childhood pulmonary arterial hypertension

    PubMed Central

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

    2014-01-01

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

  6. Are Hemodynamics Surrogate Endpoints in Pulmonary Arterial Hypertension?

    PubMed Central

    Ventetuolo, Corey E.; Gabler, Nicole B.; Fritz, Jason S.; Smith, K. Akaya; Palevsky, Harold I.; Klinger, James R.; Halpern, Scott D.; Kawut, Steven M.

    2014-01-01

    Background While frequently assessed in trials and clinical practice, hemodynamic response to therapy has never been validated as a surrogate endpoint for clinical events in pulmonary arterial hypertension (PAH). Methods and Results We performed a patient-level pooled analysis of four randomized placebo-controlled trials to determine if treatment-induced changes in hemodynamic values at 12 weeks accounted for the relationship between treatment assignment and the probability of early clinical events (death, lung transplantation, atrial septostomy, PAH hospitalization, withdrawal for clinical worsening, escalation in PAH therapy). We included 1119 subjects with PAH. The median (interquartile range) age was 48 (37 – 59), and 23% were men. 656 (59%) received active therapy (101 [15%] iloprost, 118 [18%] sitaxsentan, 204 [31%] sildenafil, and 233 [36%] subcutaneous treprostinil). Active treatment significantly lowered right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), and pulmonary vascular resistance and increased cardiac output and index (p < 0.01 for all). Changes in hemodynamic values (except for RAP and mPAP) were significantly associated with the risk of a clinical event (p ≤ 0.01 for all). While active treatment approximately halved the odds of a clinical event compared to placebo (p < 0.001), changes in hemodynamics accounted for only 1.2 – 13.9% of the overall treatment effect. Conclusions Treatment-induced changes in hemodynamics at 12 weeks only partially explain the impact of therapy on the probability of early clinical events in PAH. These findings suggest that resting hemodynamics are not valid surrogate endpoints for short-term events in PAH clinical trials. PMID:24951771

  7. Association of Parental Hypertension With Arterial Stiffness in Nonhypertensive Offspring: The Framingham Heart Study.

    PubMed

    Andersson, Charlotte; Quiroz, Rene; Enserro, Danielle; Larson, Martin G; Hamburg, Naomi M; Vita, Joseph A; Levy, Daniel; Benjamin, Emelia J; Mitchell, Gary F; Vasan, Ramachandran S

    2016-09-01

    High arterial stiffness seems to be causally involved in the pathogenesis of hypertension. We tested the hypothesis that offspring of parents with hypertension may display higher arterial stiffness before clinically manifest hypertension, given that hypertension is a heritable condition. We compared arterial tonometry measures in a sample of 1564 nonhypertensive Framingham Heart Study third-generation cohort participants (mean age: 38 years; 55% women) whose parents were enrolled in the Framingham Offspring Study. A total of 468, 715, and 381 participants had 0 (referent), 1, and 2 parents with hypertension. Parental hypertension was associated with greater offspring mean arterial pressure (multivariable-adjusted estimate=2.9 mm Hg; 95% confidence interval, 1.9-3.9, and 4.2 mm Hg; 95% confidence interval, 2.9-5.5, for 1 and 2 parents with hypertension, respectively; P<0.001 for both) and with greater forward pressure wave amplitude (1.6 mm Hg; 95% confidence interval, 0.6-2.7, and 1.9 mm Hg; 95% confidence interval, 0.6-3.2, for 1 and 2 parents with hypertension, respectively; P=0.003 for both). Carotid-femoral pulse wave velocity and augmentation index displayed similar dose-dependent relations with parental hypertension in sex-, age-, and height-adjusted models, but associations were attenuated on further adjustment. Offspring with at least 1 parent in the upper quartile of augmentation index and carotid-femoral pulse wave velocity had significantly higher values themselves (P≤0.02). In conclusion, in this community-based sample of young, nonhypertensive adults, we observed greater arterial stiffness in offspring of parents with hypertension. These observations are consistent with higher vascular stiffness at an early stage in the pathogenesis of hypertension. © 2016 American Heart Association, Inc.

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

    PubMed

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

    2016-01-01

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

  9. Association of Hypertension With Erectile Function in Chronic Peripheral Arterial Insufficiency Patients

    PubMed Central

    Spessoto, Luis Cesar Fava; Facio, Fernando Nestor; de Arruda, Jose Germano Ferraz; Arruda, Pedro Francisco F.; Gatti, Marcio; Antoniassi, Thiago Silveira; Facio, Maria Fernanda Warick; de Godoy, Jose Maria Pereira

    2016-01-01

    Background Risk factors may influence the improvement or worsening of erectile dysfunction (ED). The aim of the current study was to evaluate the effect of systemic hypertension on ED in patients with peripheral arterial disease. Methods The effect of hypertension on ED was assessed in 125 consecutive patients in a cross-sectional quantitative study. The ages of the patients ranged from 19 to 88 years old (mean: 59.82 ± 10.48 years). The only exclusion criterion was the amputation of one or both legs. The ankle-arm index was assessed and the international index of ED questionnaire was applied to all participants in the study. Results Of the 125 patients, 22 (17.6%) had mild (grade 1), 50 (40.0%) had moderate (grade 2) and 53 (42.4%) had severe (grade 3) ED. Hypertensive patients have more ED, with ED in hypertensive patients being associated to chronic arterial disease. However, in comparison with normotensive patients, hypertension exerts an immediate protective effect on erectile function. Conclusions In conclusion, although erectile function is initially protected by systemic arterial hypertension in patients with chronic arterial disease, both chronic arterial disease and ED deteriorate over the long term in hypertensive patients. PMID:27429678

  10. Effects of Different Pulmonary Vasodilators on Arterial Saturation in a Model of Pulmonary Hypertension

    PubMed Central

    Becker, Eva Maria; Stasch, Johannes-Peter; Bechem, Martin; Keldenich, Jörg; Klipp, Alexandra; Schaefer, Katja; Ulbrich, Hannes-Friedrich; Truebel, Hubert

    2013-01-01

    Background Approved therapies for pulmonary arterial hypertension can induce oxygen desaturation when administered to patients with secondary forms of pulmonary hypertension (PH), probably due to an increase in ventilation/perfusion mismatch. Thus, so far these treatments have largely failed in secondary forms of PH. Methods We established an animal model of heterogeneous lung ventilation to evaluate the desaturation potential of mechanistically distinct vasoactive drugs launched or currently in clinical development for the treatment of PH. Single-lung ventilation was induced in five groups (N = 6) of anesthetized minipigs (7 weeks, 4 to 5 kg BW), and their hemodynamic parameters were monitored before and after intravenous injection of control (vehicle only), endothelin antagonist (bosentan; 0.3, 1, 3, 10 mg/kg), phosphodiesterase type 5 inhibitor (sildenafil; 3, 10, 30, 100 µg/kg), and soluble guanylate cyclase stimulators (BAY 41–8543 and riociguat; 1, 3, 10, 30 µg/kg). Cumulative doses were administered before successive unilateral ventilation cycles. The doses were chosen to achieve equal effect on blood pressure by the different pharmacologic principles. Results Single-lung ventilation resulted in transient increases in mean pulmonary artery pressure (mPAP) and desaturation. In contrast to control, all drugs dose-dependently decreased hypoxic mPAP (a positive treatment effect) and increased area under the arterial hemoglobin saturation curve (unwanted desaturation effect). Riociguat and bosentan reduced hypoxic mPAP to the greatest extent, while the soluble guanylate cyclase stimulators riociguat and BAY 41–8543 lowered arterial oxygen saturation of hemoglobin the least. Conclusions Future investigations will be required to confirm these findings in clinical settings. PMID:24015306

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

    PubMed

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

    2012-05-01

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

  12. Prevalence of chronic obstructive pulmonary disease among patients with systemic arterial hypertension without respiratory symptoms.

    PubMed

    Rabahi, Marcelo Fouad; Pereira, Sheila Alves; Silva Júnior, José Laerte Rodrigues; de Rezende, Aline Pacheco; Castro da Costa, Adeliane; de Sousa Corrêa, Krislainy; Conde, Marcus Barreto

    2015-01-01

    The diagnosis of chronic obstructive pulmonary disease (COPD) is often delayed until later stages of the disease. The purpose of the present study was to determine the prevalence of COPD among adults on treatment for systemic arterial hypertension independently of the presence of respiratory symptoms. This cross-sectional study included adults aged ≥40 years with tobacco/occupational exposure and systemic arterial hypertension diagnosed at three Primary Health Care facilities in Goiania, Brazil. Patients were evaluated using a standardized respiratory questionnaire and spirometry. COPD prevalence was measured considering the value of forced vital capacity and/or forced expiratory volume in 1 second <0.70. Of a total of 570 subjects, 316 (55%) met inclusion criteria and were invited to participate. Two hundred and thirty-three (73.7%) patients with arterial hypertension reported at least one respiratory symptom, while 83 (26.3%) reported no respiratory symptoms; 41 (17.6%) patients with arterial hypertension and at least one respiratory symptom, and 10 (12%) patients with arterial hypertension but no respiratory symptoms were diagnosed with COPD (P=0.24). The prevalence of COPD in people with no previous COPD diagnosis was greater among those with no respiratory symptoms (100%) than among those with respiratory symptoms (56.1%) (P=0.01). Our findings suggest that regardless of the presence of respiratory symptoms, individuals aged ≥40 years with tobacco/occupational exposure and arterial hypertension may benefit from spirometric evaluation.

  13. Prevalence of chronic obstructive pulmonary disease among patients with systemic arterial hypertension without respiratory symptoms

    PubMed Central

    Rabahi, Marcelo Fouad; Pereira, Sheila Alves; Silva Júnior, José Laerte Rodrigues; de Rezende, Aline Pacheco; Castro da Costa, Adeliane; de Sousa Corrêa, Krislainy; Conde, Marcus Barreto

    2015-01-01

    Background The diagnosis of chronic obstructive pulmonary disease (COPD) is often delayed until later stages of the disease. The purpose of the present study was to determine the prevalence of COPD among adults on treatment for systemic arterial hypertension independently of the presence of respiratory symptoms. Methods This cross-sectional study included adults aged ≥40 years with tobacco/occupational exposure and systemic arterial hypertension diagnosed at three Primary Health Care facilities in Goiania, Brazil. Patients were evaluated using a standardized respiratory questionnaire and spirometry. COPD prevalence was measured considering the value of forced vital capacity and/or forced expiratory volume in 1 second <0.70. Results Of a total of 570 subjects, 316 (55%) met inclusion criteria and were invited to participate. Two hundred and thirty-three (73.7%) patients with arterial hypertension reported at least one respiratory symptom, while 83 (26.3%) reported no respiratory symptoms; 41 (17.6%) patients with arterial hypertension and at least one respiratory symptom, and 10 (12%) patients with arterial hypertension but no respiratory symptoms were diagnosed with COPD (P=0.24). The prevalence of COPD in people with no previous COPD diagnosis was greater among those with no respiratory symptoms (100%) than among those with respiratory symptoms (56.1%) (P=0.01). Conclusion Our findings suggest that regardless of the presence of respiratory symptoms, individuals aged ≥40 years with tobacco/occupational exposure and arterial hypertension may benefit from spirometric evaluation. PMID:26257517

  14. Arterial stiffness evaluated by cardio-ankle vascular index (CAVI) in adolescent hypertension.

    PubMed

    Mestanik, Michal; Jurko, Alexander; Mestanikova, Andrea; Jurko, Tomas; Tonhajzerova, Ingrid

    2016-01-01

    Elevated blood pressure (BP) is a major risk factor for atherosclerosis. As the studies concerning vascular alterations in pediatric patients are rare, we aimed to study the relationship between hypertension and arterial stiffness in adolescence by novel method independent from BP during examination. Twenty nonobese adolescent boys (16.5 ± 0.4 years) with newly diagnosed essential hypertension, 20 adolescent boys (16.7 ± 0.4 years) with newly diagnosed white-coat hypertension, and 20 healthy controls matched to age and body mass index were examined. Cardio-ankle vascular index (CAVI), brachial-ankle pulse wave velocity (baPWV), pre-ejection period (PEP), and ejection time (ET) were evaluated. CAVI was significantly increased in essential hypertension patients compared with controls (p < 0.05) with no significant difference in white-coat hypertension patients. Significantly higher baPWV was found in essential and white-coat hypertension patients compared with controls (both p < 0.001). White-coat hypertension patients showed significantly shortened PEP and ET compared with controls (p < 0.01 and p < 0.001, respectively) and essential hypertension patients (both p < 0.05). For the first time, the arterial stiffness in adolescents with newly diagnosed essential and white-coat hypertension was studied using BP-independent index CAVI combined with conventional baPWV. Our study revealed significantly increased CAVI in adolescents with newly diagnosed essential hypertension compared with controls. Our findings could help to understand hypertension-atherosclerosis interaction.

  15. The molecular targets of approved treatments for pulmonary arterial hypertension

    PubMed Central

    Humbert, Marc; Ghofrani, Hossein-Ardeschir

    2016-01-01

    Until recently, three classes of medical therapy were available for the treatment of pulmonary arterial hypertension (PAH)—prostanoids, endothelin receptor antagonists and phosphodiesterase type 5 (PDE5) inhibitors. With the approval of the soluble guanylate cyclase stimulator riociguat, an additional drug class has become available targeting a distinct molecular target in the same pathway as PDE5 inhibitors. Treatment recommendations currently include the use of all four drug classes to treat PAH, but there is a lack of comparative data for these therapies. Therefore, an understanding of the mechanistic differences between these agents is critical when making treatment decisions. Combination therapy is often used to treat PAH and it is therefore important that physicians understand how the modes of action of these drugs may interact to work as complementary partners, or potentially with unwanted consequences. Furthermore, different patient phenotypes mean that patients respond differently to treatment; while a certain monotherapy may be adequate for some patients, for others it will be important to consider alternating or combining compounds with different molecular targets. This review describes how the four currently approved drug classes target the complex pathobiology of PAH and will consider the distinct target molecules of each drug class, their modes of action, and review the pivotal clinical trial data supporting their use. It will also discuss the rationale for combining drugs (or not) from the different classes, and review the clinical data from studies on combination therapy. PMID:26219978

  16. Pediatric pulmonary arterial hypertension: on the eve of growing up.

    PubMed

    Douwes, Johannes M; Berger, Rolf M F

    2017-09-01

    Current recommendations for diagnosis and treatment of pulmonary arterial hypertension (PAH) during childhood are expert opinion based, because of lacking pediatric data. In recent years, however, important pediatric data have emerged on PAH. PAH in children shows similarities as well as differences compared to adults. Neonates and children know specific clinical presentations and a hemodynamic profile that differs from adults with PAH. Children identified as acute vasodilator responders according to the criteria proposed for adults rather than the pediatric criteria have better outcome when treated with calcium channel blockers. For nonresponders, combination PAH-targeted therapy leads to improved outcome compared to monotherapy. In pediatric PAH, WHO functional class, N-terminal pro-brain natriuretic peptide and tricuspid annular plane systolic excursion were identified as surrogates for survival and therefore qualify to be treatment goals in a goal-oriented treatment strategy. In order to refine current pediatric treatment guidelines, data on efficacy of specific treatment regiments and strategies are needed. The recently validated composite endpoint of clinical worsening allows for trials that will provide these data. For the first time, evidence-based treatment goals have been identified that will allow for a goal-oriented treatment strategy. Furthermore, various prognostic predictors have been identified that may prove treatment goals in future.

  17. Tobacco smoke exposure in pulmonary arterial and thromboembolic pulmonary hypertension.

    PubMed

    Keusch, Stephan; Hildenbrand, Florian F; Bollmann, Tom; Halank, Michael; Held, Matthias; Kaiser, Ralf; Kovacs, Gabor; Lange, Tobias J; Seyfarth, Hans-Jürgen; Speich, Rudolf; Ulrich, Silvia

    2014-01-01

    Animal studies and data from a single-center study suggest that tobacco smoke exposure may be a risk factor for precapillary pulmonary hypertension (PH). We aimed to survey tobacco smoke exposure in a large PH collective and to compare it with epidemiological data from healthy subjects. This is an international, multicenter, case-control study including patients with pulmonary arterial and chronic thromboembolic PH. All patients were asked specific questions about tobacco smoke exposure. Healthy controls were retrieved from the Swiss Health Survey (n = 18,747). Overall (n = 472), 49% of PH patients were smokers and there was a clear sex difference (women 37%, men 71%). Significantly more PH men were smokers compared with healthy controls, whereas less PH women were ever active smokers. However, 50% of the non-smoking PH women were exposed to secondhand smoke, leading to a significantly higher number of tobacco smoke-exposed individuals compared to healthy controls. PH smokers were significantly younger compared to those not exposed. Active and environmental tobacco smoke exposure is common in PH. The higher prevalence of male PH smokers, the higher exposure to environmental tobacco smoke in PH women compared to healthy controls and the lower age at PH diagnosis in smokers may indicate a pathogenic role of tobacco smoke exposure in PH. © 2014 S. Karger AG, Basel.

  18. The Characteristics of Treated Pulmonary Arterial Hypertension Patients in Ontario

    PubMed Central

    Vaid, Haris M.; Camacho, Ximena; Granton, John T.; Mamdani, Muhammad M.; Yao, Zhan; Singh, Samantha; Juurlink, David N.; Gomes, Tara

    2016-01-01

    Background. There are no Canadian prevalence studies on pulmonary arterial hypertension (PAH) to date. We described the characteristics of treated PAH patients and the healthcare utilization and costs associated with PAH in a population of public drug plan beneficiaries in Ontario, Canada. Methods. A retrospective cross-sectional analysis was conducted between April 2010 and March 2011 to identify treated PAH patients using population-based health administrative databases. We investigated demographic and clinical characteristics of treated PAH patients and conducted a cohort study to determine treatment patterns, healthcare utilization, and associated costs, over a one-year follow-up period (March 2012). Results. We identified 326 treated PAH cases in Ontario's publicly funded drug plan. Overall mean age was 59.4 years (±20.3 years) and over 77% of cases were women (n = 251). Combination therapy was used to treat 22.9% (n = 69) of cases, costing an average of $4,569 (SD $1,544) per month. Median monthly healthcare costs were $264 (IQR $96–$747) for those who survived and $2,021 (IQR $993–$6,399) for those who died over a one-year period, respectively (p < 0.01). Conclusions. PAH care in Ontario is complex and has high healthcare costs. This data may help guide towards improved patient management. PMID:27445555

  19. Epoprostenol sodium for treatment of pulmonary arterial hypertension.

    PubMed

    Saito, Yukihiro; Nakamura, Kazufumi; Akagi, Satoshi; Sarashina, Toshihiro; Ejiri, Kentaro; Miura, Aya; Ogawa, Aiko; Matsubara, Hiromi; Ito, Hiroshi

    2015-01-01

    The release of endogenous prostacyclin (PGI2) is depressed in patients with pulmonary arterial hypertension (PAH). PGI2 replacement therapy by epoprostenol infusion is one of the best treatments available for PAH. Here, we provide an overview of the current clinical data for epoprostenol. Epoprostenol treatment improves symptoms, exercise capacity, and hemodynamics, and is the only treatment that has been shown to reduce mortality in patients with idiopathic PAH (IPAH) in randomized clinical trials. We have reported that high-dose epoprostenol therapy (>40 ng/kg/min) also results in marked hemodynamic improvement in some patients with IPAH. High-dose epoprostenol has a pro-apoptotic effect on PAH-PASMCs via the IP receptor and upregulation of Fas ligand (FasL) in vitro. However, long-term intravenous administration of epoprostenol is sometimes associated with catheter-related infections and leads to considerable inconvenience for the patient. In the future, the development of new routes of administration or the development of powerful PGI2 analogs, IP-receptor agonists, and gene and cell-based therapy enhancing PGI2 production with new routes of administration is required.

  20. Epoprostenol sodium for treatment of pulmonary arterial hypertension

    PubMed Central

    Saito, Yukihiro; Nakamura, Kazufumi; Akagi, Satoshi; Sarashina, Toshihiro; Ejiri, Kentaro; Miura, Aya; Ogawa, Aiko; Matsubara, Hiromi; Ito, Hiroshi

    2015-01-01

    The release of endogenous prostacyclin (PGI2) is depressed in patients with pulmonary arterial hypertension (PAH). PGI2 replacement therapy by epoprostenol infusion is one of the best treatments available for PAH. Here, we provide an overview of the current clinical data for epoprostenol. Epoprostenol treatment improves symptoms, exercise capacity, and hemodynamics, and is the only treatment that has been shown to reduce mortality in patients with idiopathic PAH (IPAH) in randomized clinical trials. We have reported that high-dose epoprostenol therapy (>40 ng/kg/min) also results in marked hemodynamic improvement in some patients with IPAH. High-dose epoprostenol has a pro-apoptotic effect on PAH-PASMCs via the IP receptor and upregulation of Fas ligand (FasL) in vitro. However, long-term intravenous administration of epoprostenol is sometimes associated with catheter-related infections and leads to considerable inconvenience for the patient. In the future, the development of new routes of administration or the development of powerful PGI2 analogs, IP-receptor agonists, and gene and cell-based therapy enhancing PGI2 production with new routes of administration is required. PMID:25999730

  1. Pulmonary endothelial cell DNA methylation signature in pulmonary arterial hypertension.

    PubMed

    Hautefort, Aurélie; Chesné, Julie; Preussner, Jens; Pullamsetti, Soni S; Tost, Jorg; Looso, Mario; Antigny, Fabrice; Girerd, Barbara; Riou, Marianne; Eddahibi, Saadia; Deleuze, Jean-François; Seeger, Werner; Fadel, Elie; Simonneau, Gerald; Montani, David; Humbert, Marc; Perros, Frédéric

    2017-08-08

    Pulmonary arterial hypertension (PAH) is a severe and incurable pulmonary vascular disease. One of the primary origins of PAH is pulmonary endothelial dysfunction leading to vasoconstriction, aberrant angiogenesis and smooth muscle cell proliferation, endothelial-to-mesenchymal transition, thrombosis and inflammation. Our objective was to study the epigenetic variations in pulmonary endothelial cells (PEC) through a specific pattern of DNA methylation. DNA was extracted from cultured PEC from idiopathic PAH (n = 11), heritable PAH (n = 10) and controls (n = 18). DNA methylation was assessed using the Illumina HumanMethylation450 Assay. After normalization, samples and probes were clustered according to their methylation profile. Differential clusters were functionally analyzed using bioinformatics tools. Unsupervised hierarchical clustering allowed the identification of two clusters of probes that discriminates controls and PAH patients. Among 147 differential methylated promoters, 46 promoters coding for proteins or miRNAs were related to lipid metabolism. Top 10 up and down-regulated genes were involved in lipid transport including ABCA1, ABCB4, ADIPOQ, miR-26A, BCL2L11. NextBio meta-analysis suggested a contribution of ABCA1 in PAH. We confirmed ABCA1 mRNA and protein downregulation specifically in PAH PEC by qPCR and immunohistochemistry and made the proof-of-concept in an experimental model of the disease that its targeting may offer novel therapeutic options. In conclusion, DNA methylation analysis identifies a set of genes mainly involved in lipid transport pathway which could be relevant to PAH pathophysiology.

  2. Oestrogen inhibition reverses pulmonary arterial hypertension and associated metabolic defects.

    PubMed

    Chen, Xinping; Austin, Eric D; Talati, Megha; Fessel, Joshua P; Farber-Eger, Eric H; Brittain, Evan L; Hemnes, Anna R; Loyd, James E; West, James

    2017-08-01

    Increased oestrogen is a strong epidemiological risk factor for development of pulmonary arterial hypertension (PAH) in patients, associated with metabolic defects. In addition, oestrogens drive penetrance in mice carrying mutations in bone morphogenetic protein receptor type II (BMPR2), the cause of most heritable PAH. The goal of the present study was to determine whether inhibition of oestrogens was effective in the treatment of PAH in these mice.The oestrogen inhibitors fulvestrant and anastrozole were used in a prevention and treatment paradigm in BMPR2 mutant mice, and tamoxifen was used for treatment. In addition, BMPR2 mutant mice were crossed onto oestrogen receptor (ESR)1 and ESR2 knockout backgrounds to assess receptor specificity. Haemodynamic and metabolic outcomes were measured.Oestrogen inhibition both prevented and treated PAH in BMPR2 mutant mice. This was associated with reduction in metabolic defects including oxidised lipid formation, insulin resistance and rescue of peroxisome proliferator-activated receptor-γ and CD36. The effect was mediated primarily through ESR2, but partially through ESR1.Our data suggest that trials of oestrogen inhibition in human PAH are warranted, and may improve pulmonary vascular disease through amelioration of metabolic defects. Although fulvestrant and anastrozole were more effective than tamoxifen, tamoxifen may be useful in premenopausal females, because of a reduced risk of induction of menopause. Copyright ©ERS 2017.

  3. Recent advances in the management of pulmonary arterial hypertension

    PubMed Central

    de Jesus Perez, Vinicio

    2016-01-01

    Over the past 20 years, there has been an explosion in the development of therapeutics to treat pulmonary arterial hypertension (PAH), a rare but life-threatening disorder associated with progressive elevation of pulmonary pressures and severe right heart failure. Recently, the field has seen the introduction of riociguat, a soluble guanylate cyclase stimulator, a new endothelin receptor antagonist (macitentan), and oral prostanoids (treprostinil and selexipag). Besides new drugs, there have been significant advances in defining the role of upfront combination therapy in treatment-naïve patients as well as proposed methods to deliver systemic prostanoids by use of implantable pumps. In this review, we will touch upon the most important developments in PAH therapeutics over the last three years and how these have changed the guidelines for the treatment of PAH. These exciting developments herald a new era in the treatment of PAH which will be punctuated by the use of more clinically relevant endpoints in clinical research trials and a novel treatment paradigm that may involve upfront double- or triple-combination therapy. We anticipate that the future will make use of these strategies to test the efficacy of upcoming new drugs that aspire to reduce disease progression and improve survival in patients afflicted with this devastating disease. PMID:27990270

  4. Vascular narrowing in pulmonary arterial hypertension is heterogeneous: rethinking resistance.

    PubMed

    Rol, Nina; Timmer, Esther M; Faes, Theo J C; Noordegraaf, Anton Vonk; Grünberg, Katrien; Bogaard, Harm-Jan; Westerhof, Nico

    2017-03-01

    In idiopathic pulmonary arterial hypertension (PAH), increased pulmonary vascular resistance is associated with structural narrowing of small (resistance) vessels and increased vascular tone. Current information on pulmonary vascular remodeling is mostly limited to averaged increases in wall thickness, but information on number of vessels affected and internal diameter decreases for vessels of different sizes is limited. Our aim was to quantify numbers of affected vessels and their internal diameter decrease for differently sized vessels in PAH in comparison with non-PAH patients. Internal and external diameters of transversally cut vessels were measured in five control subjects and six PAH patients. Resistance vessels were classified in Strahler orders, internal diameters 13 μm (order 1) to 500 μm (order 8). The number fraction, that is, percentage of affected vessels, and the internal diameter fraction, that is, percentage diameter of normal diameter, were calculated. In PAH, not all resistance vessels are affected. The number fraction is about 30%, that is, 70% of vessels have diameters not different from vessels of control subjects. Within each order, the decrease in diameter of affected vessels is variable with an averaged diameter fraction of 50-70%. Narrowing of resistance vessels is heterogeneous: not all vessels are narrowed, and the decrease in internal diameters, even within a single order, vary largely. This heterogeneous narrowing alone cannot explain the large resistance increase in PAH We suggest that rarefaction could be an important contributor to the hemodynamic changes.

  5. [Fluid overload and arterial hypertension in hemodialysis patients].

    PubMed

    Arkouche, Walid; Giaime, Philippe; Mercadal, Lucile

    2013-11-01

    The water sodium overload is a factor of morbi-mortality and its treatment is one of the markers of adequacy of the hemodialysis treatment. Its first clinical assessment was improved by tools such as echocardiography and ultrasonography of the inferior vena cava, the per-dialytic curve of plasma volume, measuring BNP or proBNP and by impedancemetry. The combination of the evaluation of these parameters and of the clinical situation allows one to assess the extracellular overload, the state of the blood volume and the potential of plasma refilling. The latter is a key factor of the per-dialytic hemodynamic tolerance. It is itself a determining factor in weight can be achieved at the end of the session. Getting the "dry" weight can require modifications of the prescriptions of the hemodialysis sessions, a filling by albumin even a drugs support. Finally, the overload treatment is the central part of the treatment of arterial hypertension, which has to benefit however often from antihypertensive treatment the profit of which is demonstrated.

  6. Oestrogen inhibition reverses pulmonary arterial hypertension and associated metabolic defects

    PubMed Central

    Chen, Xinping; Austin, Eric D.; Talati, Megha; Fessel, Joshua P.; Farber-Eger, Eric H.; Brittain, Evan L.; Hemnes, Anna R.; Loyd, James E.

    2017-01-01

    Increased oestrogen is a strong epidemiological risk factor for development of pulmonary arterial hypertension (PAH) in patients, associated with metabolic defects. In addition, oestrogens drive penetrance in mice carrying mutations in bone morphogenetic protein receptor type II (BMPR2), the cause of most heritable PAH. The goal of the present study was to determine whether inhibition of oestrogens was effective in the treatment of PAH in these mice. The oestrogen inhibitors fulvestrant and anastrozole were used in a prevention and treatment paradigm in BMPR2 mutant mice, and tamoxifen was used for treatment. In addition, BMPR2 mutant mice were crossed onto oestrogen receptor (ESR)1 and ESR2 knockout backgrounds to assess receptor specificity. Haemodynamic and metabolic outcomes were measured. Oestrogen inhibition both prevented and treated PAH in BMPR2 mutant mice. This was associated with reduction in metabolic defects including oxidised lipid formation, insulin resistance and rescue of peroxisome proliferator-activated receptor-γ and CD36. The effect was mediated primarily through ESR2, but partially through ESR1. Our data suggest that trials of oestrogen inhibition in human PAH are warranted, and may improve pulmonary vascular disease through amelioration of metabolic defects. Although fulvestrant and anastrozole were more effective than tamoxifen, tamoxifen may be useful in premenopausal females, because of a reduced risk of induction of menopause. PMID:28775043

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

    PubMed Central

    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-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 ETA/ETB ERA, bosentan, and the ETA-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

  8. Pharmacologic Therapy for Pulmonary Arterial Hypertension in Adults

    PubMed Central

    Taichman, Darren B.; Chung, Lorinda; Klinger, James R.; Lewis, Sandra; Mandel, Jess; Palevsky, Harold I.; Rich, Stuart; Sood, Namita; Rosenzweig, Erika B.; Trow, Terence K.; Yung, Rex; Elliott, C. Gregory; Badesch, David B.

    2014-01-01

    OBJECTIVE: Choices of pharmacologic therapies for pulmonary arterial hypertension (PAH) are ideally guided by high-level evidence. The objective of this guideline is to provide clinicians advice regarding pharmacologic therapy for adult patients with PAH as informed by available evidence. METHODS: This guideline was based on systematic reviews of English language evidence published between 1990 and November 2013, identified using the MEDLINE and Cochrane Library databases. The strength of available evidence was graded using the Grades of Recommendations, Assessment, Development, and Evaluation methodology. Guideline recommendations, or consensus statements when available evidence was insufficient to support recommendations, were developed using a modified Delphi technique to achieve consensus. RESULTS: Available evidence is limited in its ability to support high-level recommendations. Therefore, we drafted consensus statements to address many clinical questions regarding pharmacotherapy for patients with PAH. A total of 79 recommendations or consensus statements were adopted and graded. CONCLUSIONS: Clinical decisions regarding pharmacotherapy for PAH should be guided by high-level recommendations when sufficient evidence is available. Absent higher level evidence, consensus statements based upon available information must be used. Further studies are needed to address the gaps in available knowledge regarding optimal pharmacotherapy for PAH. PMID:24937180

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

    PubMed

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

    2008-05-01

    Family history of hypertension is a primary predictor of high blood pressure (BP). This study attempted to determine whether there is a gradual increase in BP and an early change in arterial elasticity characteristics between young healthy individuals with or without a family history of hypertension and whether or not this increase is apparent in males as well as in females. A total of 270 normotensive healthy individuals (112 men and 158 women, aged 16 to 30 years) with or without a family history of hypertension, participated in conventional BP measurement and completed questionnaires covering basic information and a detailed family history of cardiovascular disease. Large arterial (capacitive) compliance (C1) and small arterial (oscillatory or reflective) compliance (C2) were derived from HDI/PulseWave CR-2000 (Hypertension Diagnostics, Minneapolis, USA). Based on family history information about parents and grandparents, three groups were formed: subjects with at least one hypertensive parent (group A), subjects with only hypertensive grandparents (group B), and subjects with normotensive parents and grandparents (group C). Men in group A had lower C1 and C2 along with higher systolic BP (SBP), diastolic BP (DBP), and heart rate than men in group C. Those in group B had intermediate C1, C2 and BP levels. C1 had a linear relationship with SBP, DBP, and heart rate. In the logistic regression model of family history of hypertension, C2 was lower in young normotensive males with parental hypertension (B = -0.315, exp B = 0.73, p = 0.03), independently of SBP, DBP, and heart rate. Among females, subjects with parental hypertension had higher systolic, mean arterial pressure, and pulse pressure (p < 0.05), and there were no significant differences in C1 and C2 between those with and those without parental hypertension. In conclusion, compared with normotensive offspring of normotensive parents, normotensive offspring of hypertensive parents had increased BP and

  10. A model for geometric and mechanical adaptation of arteries to sustained hypertension.

    PubMed

    Rachev, A; Stergiopulos, N; Meister, J J

    1998-02-01

    This study aimed to model phenomenologically the dynamics of arterial wall remodeling under hypertensive conditions. Sustained hypertension was simulated by a step increase in blood pressure. The arterial wall was considered to be a thick-walled tube made of nonlinear elastic incompressible material. Remodeling rate equations were postulated for the evolution of the geometric dimensions of the hypertensive artery at the zero-stress state, as well as for one of the material constants in the constitutive equations. The driving stimuli for the geometric adaptation are the normalized deviations of wall stresses from their values under normotensive conditions. The geometric dimensions are modulated by the evolution of the deformed inner radius, which serves to restore the level of the flow-induced shear stresses at the arterial endothelium. Mechanical adaptation is driven by the difference between the area compliance under hypertensive and normotensive conditions. The predicted time course of the geometry and mechanical properties of arterial wall are in good qualitative agreement with published experimental findings. The model predicts that the geometric adaptation maintains the stress distribution in arterial wall to its control level, while the mechanical adaptation restores the normal arterial function under induced hypertension.

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

    NASA Astrophysics Data System (ADS)

    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.

  12. Skinfold thickness as a predictor of arterial stiffness: obesity and fatness linked to higher stiffness measurements in hypertensive patients.

    PubMed

    Selcuk, Ali; Bulucu, Fatih; Kalafat, Firdevs; Cakar, Mustafa; Demirbas, Seref; Karaman, Murat; Ay, Seyid Ahmet; Saglam, Kenan; Balta, Sevket; Demirkol, Sait; Arslan, Erol

    2013-01-01

    Hypertensive patients have strong evidence of endothelial dysfunction. Some novel endothelial dysfunction parameters such as pulse wave velocity (PWV), augmentation index (AIx), and central aortic pressure (CAP) have been investigated as predictive markers of atherosclerosis. It is well known that obesity has relationships with endothelial dysfunction and atherosclerosis. We aimed to investigate relationships between anthropometric measurements and arterial stiffness parameters in essentially hypertensive patients. The study population included 100 patients (56 females, 44 males) newly or formerly diagnosed as essentially hypertensive in an outpatient clinic. Arterial stiffness measurements, including PWV, AIx, CAP, and body mass index (BMI); waist circumference, hip circumference; waist/hip ratio; and triceps, biceps, subscapular, and suprailiac skinfold thicknesses were also applied to all the study patients. Then, the relationships between BMI, anthropometric measurements, and arterial stiffness parameters were investigated. The mean systolic arterial blood pressure of the study population was 135.85 ± 15.27 mm Hg and the mean diastolic arterial blood pressure of the study population was 84.17 ± 9.58 mm Hg. The parameters such as PWV, AIx, and CAP measured for arterial stiffness had correlations between BMI and different anthropometric measurements. The statistically significant correlations were present between PWV and triceps skinfold thickness (TST) (r = 0.377, P < .001) and it was also seen when regression analysis was performed (PWV = 6.41 + [0.072 × TST]; R(2) = 0.142, F[1-98] = 16.23, P < .001). Triceps skinfold thickness among these correlations may be used to estimate the carotid-femoral PWV, which is an indicator of subclinical organ damage due to hypertension.

  13. HDAC6: A Novel Histone Deacetylase Implicated in Pulmonary Arterial Hypertension.

    PubMed

    Boucherat, Olivier; Chabot, Sophie; Paulin, Roxane; Trinh, Isabelle; Bourgeois, Alice; Potus, François; Lampron, Marie-Claude; Lambert, Caroline; Breuils-Bonnet, Sandra; Nadeau, Valérie; Paradis, Renée; Goncharova, Elena A; Provencher, Steeve; Bonnet, Sébastien

    2017-07-03

    Pulmonary arterial hypertension (PAH) is a vascular remodeling disease with limited therapeutic options. Although exposed to stressful conditions, pulmonary artery (PA) smooth muscle cells (PASMCs) exhibit a "cancer-like" pro-proliferative and anti-apoptotic phenotype. HDAC6 is a cytoplasmic histone deacetylase regulating multiple pro-survival mechanisms and overexpressed in response to stress in cancer cells. Due to the similarities between cancer and PAH, we hypothesized that HDAC6 expression is increased in PAH-PASMCs to face stress allowing them to survive and proliferate, thus contributing to vascular remodeling in PAH. We found that HDAC6 is significantly up-regulated in lungs, distal PAs, and isolated PASMCs from PAH patients and animal models. Inhibition of HDAC6 reduced PAH-PASMC proliferation and resistance to apoptosis in vitro sparing control cells. Mechanistically, we demonstrated that HDAC6 maintains Ku70 in a hypoacetylated state, blocking the translocation of Bax to mitochondria and preventing apoptosis. In vivo, pharmacological inhibition of HDAC6 improved established PAH in two experimental models and can be safely given in combination with currently approved PAH therapies. Moreover, Hdac6 deficient mice were partially protected against chronic hypoxia-induced pulmonary hypertension. Our study shows for the first time that HDAC6 is implicated in PAH development and represents a new promising target to improve PAH.

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

    PubMed

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

    2016-12-01

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

  15. MR and CT imaging of the structural and functional changes of pulmonary arterial hypertension

    PubMed Central

    Schiebler, Mark L.; Bhalla, Sanjeev; Runo, James; Jarjour, Nizar; Roldan, Alejandro; Chesler, Naomi; François, Christopher J.

    2013-01-01

    The current Dana Point classification system (2009) divides elevation of pulmonary artery pressure into Pulmonary Arterial Hypertension (PAH) and Pulmonary Hypertension (PH). Fortunately, pulmonary arterial hypertension (PAH) is not a common disease. However, with the aging of the first world’s population, heart failure is now an important cause of pulmonary hypertension with up to 9% of the population involved. PAH is usually asymptomatic until late in the disease process. While there are indirect features of PAH found on noninvasive imaging studies, the diagnosis and management still requires right heart catheterization. Imaging features of PAH include: 1. Enlargement of the pulmonary trunk and main pulmonary arteries, 2. Decreased pulmonary arterial compliance, 3. Tapering of the peripheral pulmonary arteries, 4. Enlargement of the inferior vena cava, and 5. Increased mean transit time. The chronic requirement to generate high pulmonary arterial pressures measurably affects the right heart and main pulmonary artery. This change in physiology causes the following structural and functional alterations that have been shown to have prognostic significance: Relative area change of the pulmonary trunk, RVSVindex, RVSV, RVEDVindex, LVEDVindex, and baseline RVEF <35%. All of these variables can be quantified non-invasively and followed longitudinally in each patient using MRI to modify the treatment regimen. Untreated PAH frequently results in a rapid clinical decline and death within 3 years of diagnosis. Unfortunately, even with treatment, less than 1/2 of these patients are alive at four years. PMID:23612440

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

    PubMed

    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.

  17. Extracranial carotid artery aneurysm due to Behcet's disease.

    PubMed

    Albeyoglu, Sebnem; Cinar, Bayer; Eren, Tunc; Filizcan, Ugur; Bayserke, Olgar; Aslan, Cenk

    2010-12-01

    Behçet's disease is a chronic systemic inflammatory disorder associated with recurrent oral and genital ulcers and iritis. Vascular lesions are encountered in 7%-29% of patients, gravely affecting the course of the disease. Extracranial carotid aneurysms due to Behçet's disease are extremely rare. We describe a surgically treated case of Behçet's disease in a 28-year-old man who presented with a rapidly enlarging left common carotid artery aneurysm.

  18. The dissociation of arterial hypertension and lupus glomerulonephritis in systemic lupus erythematosus.

    PubMed

    Petrin, J; Rozman, B; Dolenc, P; Logar, D; Bozic, B; Vizjak, A; Ferluga, D; Jezersek, P

    1993-06-01

    In spite of several articles questioning the general opinion that arterial hypertension in patients with systemic lupus erythematosus (SLE) is only the consequence of lupus glomerulonephritis (LGN), this still remains the usual pathophysiologic explanation. The purpose of this study was to explore the correlations between hypertension and LGN and to assess the importance of hypertension control for the prognosis of patients. A retrospective analysis of 173 patients with SLE over a period of 14 years was performed. For most of the patients, data were available from regular follow-up visits over an average of 6 years. Our results show a dissociation of hypertension and LGN and an association of hypertension and renal dysfunction. Severe hypertensive renal vascular lesions correlated well with a decrease of renal function. Successful treatment of hypertension is therefore essential in order to prevent deterioration of renal function in patients with LGN.

  19. [Bilateral pulmonary artery occlusion due to primary pulmonary artery sarcoma; report of a case].

    PubMed

    Shingaki, Masami; Kobayashi, Yutaka

    2014-07-01

    60-year-old female who complained of severe dyspnea was admitted with a diagnosis of massive pulmonary embolism. An emergency operation was undertaken due to right side heart failure. Under extracorporeal circulation with beating heart, large, white and smooth surface mass which was originated from right pulmonary artery was removed. Pathology of the mass showed low differentiated sarcoma. No evidence of other primary lesion by positron emission tomography-computed tomography (PET-CT) suggested primary pulmonary artery sarcoma. We scheduled total resection of the right lung, however postoperative CT showed large mass occupying from right pulmonary artery to main pulmonary trunk. Palliative chemo radiation therapy was introduced. Pulmonary artery sarcoma mimicking pulmonary thromboembolism is so malignant that the diagnosis and treatment should not be delayed.

  20. Failure and Success of Percutaneous Angioplasty in a Hypertensive Child with Bilateral Renal Artery Stenosis

    SciTech Connect

    Giavroglou, Constantinos; Tsifountoudis, Ioannis; Boutzetis, Theodoros; Kiskinis, Dimitrios

    2009-01-15

    We describe the clinical course of a 5-year-old girl with severe arterial hypertension that was uncontrollable with antihypertensive medication. Renal angiography revealed bilateral renal artery stenoses. Because percutaneous transluminal renal angioplasty (PTRA) failed to dilate the stenotic lesions, a renal artery bypass grafting in both renal arteries was performed. The patient remained normotensive for 7 months, and after that the arterial pressure increased again. Digital subtraction angiography demonstrated stenosis at the peripheral and central anastomosis of the vein graft that was used for revascularization of the left kidney. PTRA was decided on and successful patency was achieved. The patient has now been normotensive for a period of 5 years.

  1. Acute left main coronary artery thrombosis due to cocaine use.

    PubMed

    Apostolakis, Efstratios; Tsigkas, Grigorios; Baikoussis, Nikolaos G; Koniari, Ioanna; Alexopoulos, Dimitrios

    2010-08-19

    It is common knowledge that cocaine has been linked to the development of various acute and chronic cardiovascular complications including acute coronary syndromes. We present a young, male patient, drug abuser who underwent CABG due to anterolateral myocardial infarction. Our presentation is one of the very rare cases reported in literature regarding acute thrombosis of left main coronary artery related to cocaine use, in a patient with normal coronary arteries, successfully operated. Drug-abusers seem to have increased mortality and morbidity after surgery and high possibility for stent thrombosis after percutaneous coronary interventions, because of their usually terrible medical compliance and coexistent several problems of general health. There are no specific guidelines about treatment of thrombus formation in coronary arteries, as a consequence of cocaine use. So, any decision making concerning the final treatment of these patient is a unique and individualized approach. We strongly recommend that all these patients should be treated surgically, especially patients with thrombus into the left main artery.

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

    PubMed Central

    Jochmann, Nicoline; Kiecker, Felix; Borges, Adrian C; Hofmann, Maja A; Eddicks, Stephan; Sterry, Wolfram; Baumann, Gert; Trefzer, Uwe

    2005-01-01

    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. PMID:16138923

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

    PubMed

    Hardin, Elizabeth Ashley; Chin, Kelly M

    2016-01-01

    Pulmonary arterial hypertension is characterized by abnormalities in the small pulmonary arteries including increased vasoconstriction, vascular remodeling, proliferation of smooth muscle cells, and in situ thrombosis. Selexipag, a novel, oral prostacyclin receptor agonist, has been shown to improve hemodynamics in a phase II clinical trial and reduce clinical worsening in a large phase III clinical trial involving patients with pulmonary arterial hypertension. In this paper, we describe the prostacyclin signaling pathway, currently available oral prostanoid medications, and the development and clinical use of selexipag.

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

    PubMed Central

    Hardin, Elizabeth Ashley; Chin, Kelly M

    2016-01-01

    Pulmonary arterial hypertension is characterized by abnormalities in the small pulmonary arteries including increased vasoconstriction, vascular remodeling, proliferation of smooth muscle cells, and in situ thrombosis. Selexipag, a novel, oral prostacyclin receptor agonist, has been shown to improve hemodynamics in a phase II clinical trial and reduce clinical worsening in a large phase III clinical trial involving patients with pulmonary arterial hypertension. In this paper, we describe the prostacyclin signaling pathway, currently available oral prostanoid medications, and the development and clinical use of selexipag. PMID:27895464

  5. Role of the glomerular-tubular imbalance with tubular predominance in the arterial hypertension pathophysiology.

    PubMed

    Fox, María Ofelia Barber; Gutiérrez, Ernesto Barber

    2013-09-01

    In previous investigations we caused renal tubular reabsorption preponderance relating to the glomerular filtration (Glomerular-tubular imbalance) and we observed that this fact conducted to volume expansion and development of arterial hypertension, in rats that previously were normotens. We based on this evidence and other which are reflected in the literature arrived at the following hypothesis: a greater proportion of tubular reabsorption relating to the filtered volume is the base of the establishment of the glomerular-tubular imbalance with tubular predominance (GTI-T), which favors to the Na(+)-fluid retention and volume expansion. All of which conduced to arterial hypertension. These facts explain a primary hypertensive role of the kidney, consistent with the results of renal transplants performed in different lines of hypertensive rats and their respective controls and in humans: hypertension can be transferred with the kidney. GTI-T aims to be, a common phenomenon involved in the hypertension development in the multiple ways which is manifested the hypertensive syndrome. In secondary hypertension, GTI-T is caused by significant disruptions of hormone secretions that control renal function, or obvious vascular or parenchymal damage of these organs. In primary hypertension the GTI-T has less obvious causes inherently developed in the kidney, including humoral, cellular and subcellular mechanisms, which may insidiously manifest under environmental factors influence, resulting in insidious development of hypertension. This would explain the state of prehypertension that these individuals suffer. So it has great importance to study GTI-T before the hypertension is established, because when hypertensive state is established, other mechanisms are installed and they contribute to maintain the hypertension. Our hypothesis may explaining the inability of the kidneys to excrete salt and water in hypertension, as Guyton and colleagues have expressed and constitutes a

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

    PubMed

    Zemancíková, Anna; Török, Jozef

    2013-08-31

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

  7. Preventing deaths due to the hypertensive disorders of pregnancy.

    PubMed

    von Dadelszen, Peter; Magee, Laura A

    2016-10-01

    In this chapter, taking a life cycle and both civil society and medically oriented approach, we will discuss the contribution of the hypertensive disorders of pregnancy (HDPs) to maternal, perinatal and newborn mortality and morbidity. Here we review various interventions and approaches to preventing deaths due to HDPs and discuss effectiveness, resource needs and long-term sustainability of the different approaches. Societal approaches, addressing sustainable development goals (SDGs) 2.2 (malnutrition), 3.7 (access to sexual and reproductive care), 3.8 (universal health coverage) and 3c (health workforce strengthening), are required to achieve SDGs 3.1 (maternal survival), 3.2 (perinatal survival) and 3.4 (reduced impact of non-communicable diseases (NCDs)). Medical solutions require greater clarity around the classification of the HDPs, increased frequency of effective antenatal visits, mandatory responses to the HDPs when encountered, prompt provision of life-saving interventions and sustained surveillance for NCD risk for women with a history of the HDPs.

  8. Prevalence of pseudoresistant hypertension due to inaccurate blood pressure measurement

    PubMed Central

    Bhatt, Hemal; Siddiqui, Mohammed; Judd, Eric; Oparil, Suzanne; Calhoun, David

    2016-01-01

    Background The prevalence of pseudoresistant hypertension (HTN) due to inaccurate BP measurement remains unknown. Methods Triage BP measurements and measurements obtained at the same clinic visit by trained physicians were compared in consecutive adult patients referred for uncontrolled resistant HTN (RHTN). Triage BP measurements were taken by the clinic staff during normal intake procedures. BP measurements were obtained by trained physicians using the BpTRU device. The prevalence of uncontrolled RHTN and differences in BP measurements were compared. Results Of 130 patients with uncontrolled RHTN, 33.1% (n=43) were falsely identified as having uncontrolled RHTN based on triage BP measurements. The median (IQR) of differences in systolic BP between pseudoresistant and true resistant groups were 23 (17 – 33) mm Hg and 13 (6 – 21) mm Hg, respectively (P=0.0001). The median (IQR) of differences in diastolic BP between the two groups were 12 (7 – 18) mm Hg and 8 (4 – 11) mm Hg, respectively (P=0.001). Conclusion Triage BP technique overestimated the prevalence of uncontrolled RHTN in approximately 33% of the patients emphasizing the importance of obtaining accurate BP measurements. PMID:27129931

  9. Theoretical study of the effect of stress-dependent remodeling on arterial geometry under hypertensive conditions.

    PubMed

    Rachev, A

    1997-08-01

    Remodeling of arterial geometry was studied on the basis of a theoretical model. Sustained hypertension was simulated by a step increase in blood pressure. The artery was considered to be a thick-walled two-layer tube made of nonlinear elastic incompressible material. The basic hypothesis is that the artery remodels its zero-stress configuration in such a way that the strain and stress distributions in the arterial wall under hypertensive conditions are the same as under normotensive conditions. Using this hypothesis, a method for determining the geometrical dimensions of the zero-stress configuration of the hypertensive artery was proposed. To ensure uniqueness of the solution, two side conditions on the remodeling process are imposed: (a) the inner radius of the artery in the unloaded state remains unchanged; and (b) the ratio between the thickness of the inner and outer layer of the hypertensive artery in the zero-stress configuration is known. The model predicts that the arterial wall remodeling causes: (i) an increase of the wall thickness both in the unloaded and physiological states; (ii) an increase of the inner diameter of the hypertensive vessel under high pressure compared to the diameter of the normotensive artery under normal pressure; (iii) the opened-up configuration which arises when the unloaded arterial segment is cut radially still contains residual strains and stresses. These results are consistent with published experimental findings. It is speculated that the origin of residual stresses that exist in the unloaded and opened-up configurations is the stress-modulated growth.

  10. Nitric oxide deficiency and endothelial dysfunction in pulmonary arterial hypertension.

    PubMed

    Klinger, James R; Abman, Steven H; Gladwin, Mark T

    2013-09-15

    Nitric oxide (NO) signaling plays a major role in modulating vascular tone and remodeling in the pulmonary circulation, but its role in the pathogenesis of pulmonary vascular diseases is still not completely understood. Numerous abnormalities of NO synthesis and signaling have been identified in animal models of pulmonary vascular disease and in humans with pulmonary hypertension. Many of these abnormalities have become targets of new therapies for the treatment of pulmonary hypertension. However, it is unclear to what extent alterations in NO signaling contribute to pulmonary hypertensive responses or merely reflect abnormalities induced by the underlying disease. This perspective examines the current understanding of altered NO signaling in pulmonary hypertensive diseases and discusses how these alterations may contribute to the pathogenesis of pulmonary hypertension. The efficacy and limitations of presently available therapies for pulmonary hypertension that target NO signaling are reviewed along with an update on investigational therapies that use this pathway to reverse pulmonary hypertensive changes.

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

    SciTech Connect

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

    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

  12. [Hypertension due to persistent hypokalemia: a complex case].

    PubMed

    Abad Cardiel, María; Ruisánchez Muñumel, Juan Vicente; Martell Claros, Nieves

    2009-11-01

    High grade of suspect must be present to diagnose some of the multiple causes of secondary blood hypertension. In the literature, there are reports that describe the coincidence of 2 different aetiologies of secondary hypertension in one patient, but both of endocrine origin. This one is the first time that a case with simultaneity of fibromuscular dysplasia and hyperaldosteronism in the same patient is described. This is the case of a 40-year-sold hypertensive patient, with a normal previous study of secondary hypertension, which after presenting HELLP syndrome (hemolysis, elevated liver enzymes and low platelet count) during a pregnancy with foetal death was studied again to rule out a secondary aetiology for her hypertension. After various studies were performed the patient was diagnosed as having two secondary causes for her hypertension: primary hyperaldosteronism and fibromuscular dysplasia, and after a guided treatment, optimal control for blood pressure was attainted. With this clinical case we show the importance of the clinical suspicion and the need for perseverance in the diagnoses of secondary blood hypertension, and also the exclusivity of this case.

  13. Rapid Transition from Inhaled Iloprost to Inhaled Treprostinil in Patients with Pulmonary Arterial Hypertension

    PubMed Central

    Bourge, Robert C; Tapson, Victor F; Safdar, Zeenat; Benza, Raymond L; Channick, Richard N; Rosenzweig, Erika B; Shapiro, Shelley; White, Richard James; McSwain, Christopher Shane; Gotzkowsky, Stephen Karl; Nelsen, Andrew C; Rubin, Lewis J

    2013-01-01

    Background Inhaled treprostinil is a prostacyclin analog approved for the treatment of pulmonary arterial hypertension (PAH) that may provide a more convenient treatment option for patients receiving inhaled iloprost while maintaining the clinical benefit of inhaled prostacyclin therapy. Aims In this open-label safety study, 73 PAH patients were enrolled with primarily World Health Organization Class II (56%) or III (42%) symptoms. At baseline, most patients (93%) were receiving 5 μg of iloprost per dose but 38% of patients reported a dosing frequency below the labeled rate of 6–9 times daily. Patients initiated inhaled treprostinil at 3 breaths four times daily (qid) at the immediate next scheduled iloprost dose. The primary objective was to assess the safety of rapid transition from iloprost to inhaled treprostinil; clinical status and quality of life were also assessed. Results Most patients (84%) achieved the target treprostinil dose of 9 breaths qid and remained on study until transition to commercial therapy (89%). The most frequent adverse events (AEs) were cough (74%), headache (44%), and nausea (30%), and five patients prematurely discontinued study drug due to AE (n = 3), disease progression (n = 1), or death (n = 1). At week 12, the time spent on daily treatment activities was reduced compared to baseline, with a mean total savings of 1.4 h per day. Improvements were also observed at week 12 for 6-min walk distance (+16.0; P < 0.001), N-terminal pro-B-type natriuretic peptide (−74 pg/mL; P = 0.001), and the Cambridge Pulmonary Hypertension Outcome Review (all domains P < 0.001). Conclusions Pulmonary arterial hypertension patients can be safely transitioned from inhaled iloprost to inhaled treprostinil while maintaining clinical status. PMID:22970909

  14. Benefits of skeletal-muscle exercise training in pulmonary arterial hypertension: The WHOLEi+12 trial.

    PubMed

    González-Saiz, Laura; Fiuza-Luces, Carmen; Sanchis-Gomar, Fabian; Santos-Lozano, Alejandro; Quezada-Loaiza, Carlos A; Flox-Camacho, Angela; Munguía-Izquierdo, Diego; Ara, Ignacio; Santalla, Alfredo; Morán, María; Sanz-Ayan, Paz; Escribano-Subías, Pilar; Lucia, Alejandro

    2017-03-15

    Pulmonary arterial hypertension is often associated with skeletal-muscle weakness. The purpose of this randomized controlled trial was to determine the effects of an 8-week intervention combining muscle resistance, aerobic and inspiratory pressure-load exercises on upper/lower-body muscle power and other functional variables in patients with this disease. Participants were allocated to a control (standard care) or intervention (exercise) group (n=20 each, 45±12 and 46±11years, 60% women and 10% patients with chronic thromboembolic pulmonary hypertension per group). The intervention included five, three and six supervised (inhospital) sessions/week of aerobic, resistance and inspiratory muscle training, respectively. The primary endpoint was peak muscle power during bench/leg press; secondary outcomes included N-terminal pro-brain natriuretic peptide levels, 6-min walking distance, five-repetition sit-to-stand test, maximal inspiratory pressure, cardiopulmonary exercise testing variables (e.g., peak oxygen uptake), health-related quality of life, physical activity levels, and safety. Adherence to training sessions averaged 94±0.5% (aerobic), 98±0.3% (resistance) and 91±1% (inspiratory training). Analysis of variance showed a significant interaction (group×time) effect for leg/bench press (P<0.001/P=0.002), with both tests showing an improvement in the exercise group (P<0.001) but not in controls (P>0.1). We found a significant interaction effect (P<0.001) for five-repetition sit-to-stand test, maximal inspiratory pressure and peak oxygen uptake (P<0.001), indicating a training-induced improvement. No major adverse event was noted due to exercise. An 8-week exercise intervention including aerobic, resistance and specific inspiratory muscle training is safe for patients with pulmonary arterial hypertension and yields significant improvements in muscle power and other functional variables. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Rapid transition from inhaled iloprost to inhaled treprostinil in patients with pulmonary arterial hypertension.

    PubMed

    Bourge, Robert C; Tapson, Victor F; Safdar, Zeenat; Benza, Raymond L; Channick, Richard N; Rosenzweig, Erika B; Shapiro, Shelley; White, R James; McSwain, Christopher Shane; Gotzkowsky, Stephen Karl; Nelsen, Andrew C; Rubin, Lewis J

    2013-02-01

    Inhaled treprostinil is a prostacyclin analog approved for the treatment of pulmonary arterial hypertension (PAH) that may provide a more convenient treatment option for patients receiving inhaled iloprost while maintaining the clinical benefit of inhaled prostacyclin therapy. In this open-label safety study, 73 PAH patients were enrolled with primarily World Health Organization Class II (56%) or III (42%) symptoms. At baseline, most patients (93%) were receiving 5 μg of iloprost per dose but 38% of patients reported a dosing frequency below the labeled rate of 6-9 times daily. Patients initiated inhaled treprostinil at 3 breaths four times daily (qid) at the immediate next scheduled iloprost dose. The primary objective was to assess the safety of rapid transition from iloprost to inhaled treprostinil; clinical status and quality of life were also assessed. Most patients (84%) achieved the target treprostinil dose of 9 breaths qid and remained on study until transition to commercial therapy (89%). The most frequent adverse events (AEs) were cough (74%), headache (44%), and nausea (30%), and five patients prematurely discontinued study drug due to AE (n = 3), disease progression (n = 1), or death (n = 1). At week 12, the time spent on daily treatment activities was reduced compared to baseline, with a mean total savings of 1.4 h per day. Improvements were also observed at week 12 for 6-min walk distance (+16.0; P < 0.001), N-terminal pro-B-type natriuretic peptide (-74 pg/mL; P = 0.001), and the Cambridge Pulmonary Hypertension Outcome Review (all domains P < 0.001). Pulmonary arterial hypertension patients can be safely transitioned from inhaled iloprost to inhaled treprostinil while maintaining clinical status. © 2012 Blackwell Publishing Ltd.

  16. Arterial Hypertension and other risk factors associated with cardiovascular diseases among adults1

    PubMed Central

    Radovanovic, Cremilde Aparecida Trindade; dos Santos, Lucimary Afonso; Carvalho, Maria Dalva de Barros; Marcon, Sonia Silva

    2014-01-01

    OBJECTIVE: to identify the prevalence of arterial hypertension and its association with cardiovascular risk factors among adults. METHOD: cross-sectional, population-based, descriptive study conducted with 408 adult individuals. Data were collected through a questionnaire and measurements of weight, height and waist circumference. Person's Chi-square and multiple logistic regression were used in the data analysis. RESULTS: 23.03% of the individuals reported hypertension with a higher prevalence among women. Odds Ratio indicated that smoking, body mass index, waist circumference, diabetes mellitus and dyslipidemia were positively associated with arterial hypertension. CONCLUSION: high self-reported hypertension and its association with other cardiovascular risk factors such as diabetes, obesity and dyslipidemia show the need for specific nursing interventions and the implementation of protocols focused on minimizing complications arising from hypertension, as well as to prevent the emergence of other cardiovascular diseases. PMID:25296137

  17. [Radiodiagnosis of early-stage nephroangiopathy in children with arterial hypertension].

    PubMed

    Trubnikova, K E; Trofimova, G N; Novikov, A I; Nazarov, T N

    2011-01-01

    A total of 115 children aged 13-17 years (mean age 15.77 +/- 1.89 years, 98 boys and 17 girls) with essential arterial hypertension (EAH) were examined. Of them, 70 children had stable arterial hypertension (SAH), 45 children - labile arterial hypertension (LAH). 24-h monitoring of blood pressure, triplex ultrasound study of the renal vessels were performed in all the patients. The assessment of renal hemodynamics showed that blood flow was more active in SAH patients. The clinostatic test revealed inhibition of circulation at the level of the basic trunk (by 26% in SAH and by 22% in LAH) and segmentary renal arteries (by 28% in SAG), IR ( < 0.52). The above findings confirm the action of arterioveinous bypass blood flow mechanism and provide diagnosis of nephroangiopathy at early stages of EAH.

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

    SciTech Connect

    Poreba, Rafal; Gac, Pawel; Poreba, Malgorzata; Antonowicz-Juchniewicz, Jolanta; Andrzejak, Ryszard

    2011-08-01

    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 ({beta}), augmentation index (AI) and one-point pulse wave velocity (PWV-{beta}) 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

  19. [Efficacy of emoxipin in treatment of arterial hypertension in the Far North].

    PubMed

    Vershinina, A M; Gapon, L I; Shurkevich, N P; Bazhukhina, I F; Petelina, T I; Savel'eva, N Iu

    1999-01-01

    A total of 95 hypertensive men working in duty regimen in the extreme North were examined. The men were found to have lipid metabolism disorders, activation of lipid peroxidation, decreased antioxidant defense in red cell membranes in all the examinees vs control hypertensive men living in moderate climatic zone. Effect of 2-week monotherapy with emoxipin was studied in 29 males with mild arterial hypertension free of obesity and coexisting diseases. Placebo was given to 10 patients. Emoxipin had an antihypertensive and antioxidant effects, improved structural-functional condition of erythrocytes in hypertensive patients.

  20. Pathophysiology of infantile pulmonary arterial hypertension induced by monocrotaline.

    PubMed

    Dias-Neto, Marina; Luísa-Neves, Ana; Pinho, Sónia; Gonçalves, Nádia; Mendes, Maria; Eloy, Catarina; Lopes, José M; Gonçalves, Daniel; Ferreira-Pinto, Manuel; Leite-Moreira, Adelino F; Henriques-Coelho, Tiago

    2015-06-01

    Pediatric pulmonary arterial hypertension (PAH) presents certain specific features. In this specific age group, experimental models to study the pathophysiology of PAH are lacking. To characterize hemodynamic, morphometric, and histological progression as well as the expression of neurohumoral factors and regulators of cardiac transcription in an infantile model of PAH induced by monocrotaline (MCT), eight-day-old Wistar rats were randomly injected with MCT (30 mg/kg, sc, n = 95) or equal volume of saline solution (n = 92). Animals were instrumented for biventricular hemodynamic recording 7, 14, and 21 days after MCT, whereas samples were collected at 1, 3, 7, 14, and 21 days after MCT. Different time point postinjections were defined for further analysis. Hearts and lungs were collected for morphometric characterization, assessment of right- and left-ventricle (RV and LV) cardiomyocyte diameter and collagen type-I and type-III ratio, RV collagen volume fraction, and pulmonary vessels wall thickness. mRNA quantification was undertaken for brain natriuretic peptide (BNP), endothelin-1 (ET-1), and for cardiac transcription regulators (HOP and Islet1). Animals treated with MCT at the 8th day of life presented RV hypertrophy since day 14 after MCT injection. There were no differences on the RV collagen volume fraction or collagen type-I and type-III ratio. Pulmonary vascular remodelling and PAH were present on day 21, which were accompanied by an increased expression of BNP, ET-1, HOP, and Islet1. The infantile model of MCT-induced PAH can be useful for the study of its pathophysiology and to test new therapeutic targets in pediatric age group.

  1. Small platelet microparticle levels are increased in pulmonary arterial hypertension.

    PubMed

    Nadaud, Sophie; Poirier, Odette; Girerd, Barbara; Blanc, Catherine; Montani, David; Eyries, Mélanie; Imbert-Bismut, Françoise; Pacheco, Antoine; Vigne, Jacques; Tregouet, David-Alexandre; Humbert, Marc; Soubrier, Florent

    2013-01-01

    The various aetiologies and risk factors for pulmonary arterial hypertension (PAH) lead to close phenotypes with small differences. Plasma microparticles have been shown to be increased in vascular pathologies including PAH. The aim of this study was to determine whether the levels of endothelial and platelet-derived microparticles could vary between different forms of PAH: idiopathic PAH (iPAH), heritable PAH associated with BMPR2 (Bone morphogenetic protein receptor, type II) mutation (hPAH) and PAH associated with connective tissue diseases (aPAH). Microparticles were analysed using flow cytometry in plasma from controls and iPAH, hPAH and aPAH patients. Platelet-derived MP (PMP) were defined as CD31(+)/CD41(+) and endothelial-derived MP (EMP) as CD31(+)/CD41(-). Two populations of PMP were isolated according to their size, defining small PMP (0·3-0·5 μm) and large PMP (0·5-0·9 μm). BMPR2 genotype, clinical and biologic parameters were recorded. EMP and small PMP levels in iPAH, hPAH and aPAH were similar and were significantly increased as compared with controls. No differences in large PMP levels were observed. After adjusting for age, sex, proBNP and CRP, EMP and small PMP levels did not correlate with clinical parameters. iPAH, hPAH and aPAH were characterized by increased levels of EMP and of small PMP, a new class of PMP which seems to be differentially produced than large PMP. © 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.

  2. Systematic Review of the Economic Burden of Pulmonary Arterial Hypertension.

    PubMed

    Gu, Shuyan; Hu, Huimei; Dong, Hengjin

    2016-06-01

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

  3. Pulmonary endothelial cell DNA methylation signature in pulmonary arterial hypertension

    PubMed Central

    Preussner, Jens; Pullamsetti, Soni S; Tost, Jorg; Looso, Mario; Antigny, Fabrice; Girerd, Barbara; Riou, Marianne; Eddahibi, Saadia; Deleuze, Jean-François; Seeger, Werner; Fadel, Elie; Simonneau, Gerald; Montani, David; Humbert, Marc; Perros, Frédéric

    2017-01-01

    Pulmonary arterial hypertension (PAH) is a severe and incurable pulmonary vascular disease. One of the primary origins of PAH is pulmonary endothelial dysfunction leading to vasoconstriction, aberrant angiogenesis and smooth muscle cell proliferation, endothelial-to-mesenchymal transition, thrombosis and inflammation. Our objective was to study the epigenetic variations in pulmonary endothelial cells (PEC) through a specific pattern of DNA methylation. DNA was extracted from cultured PEC from idiopathic PAH (n = 11), heritable PAH (n = 10) and controls (n = 18). DNA methylation was assessed using the Illumina HumanMethylation450 Assay. After normalization, samples and probes were clustered according to their methylation profile. Differential clusters were functionally analyzed using bioinformatics tools. Unsupervised hierarchical clustering allowed the identification of two clusters of probes that discriminates controls and PAH patients. Among 147 differential methylated promoters, 46 promoters coding for proteins or miRNAs were related to lipid metabolism. Top 10 up and down-regulated genes were involved in lipid transport including ABCA1, ABCB4, ADIPOQ, miR-26A, BCL2L11. NextBio meta-analysis suggested a contribution of ABCA1 in PAH. We confirmed ABCA1 mRNA and protein downregulation specifically in PAH PEC by qPCR and immunohistochemistry and made the proof-of-concept in an experimental model of the disease that its targeting may offer novel therapeutic options. In conclusion, DNA methylation analysis identifies a set of genes mainly involved in lipid transport pathway which could be relevant to PAH pathophysiology. PMID:28881789

  4. Cystatin C: a potential biomarker for pulmonary arterial hypertension.

    PubMed

    Fenster, Brett E; Lasalvia, Luis; Schroeder, Joyce D; Smyser, Jamey; Silveira, Lori J; Buckner, J Kern; Brown, Kevin K

    2014-05-01

    Cystatin C (CysC), a novel marker of renal function, predicts left heart failure and cardiovascular mortality. The hypothesis that serum CysC levels correlate with right ventricular (RV) morphology, function and pressure in pulmonary arterial hypertension (PAH) was tested. As part of a prospective study, 14 PAH subjects and 10 matched controls underwent same-day echocardiography, cardiac magnetic resonance imaging (CMR), and phlebotomy for CysC, brain natriuretic peptide (BNP), and N-terminal BNP (NT-ProBNP). RV ejection fraction (RVEF), end-diastolic volume, end-systolic volume and mass were calculated using CMR. RV systolic pressure (RVSP), strain and diastolic function (including tricuspid valve (TV) E velocity, A velocity, e' velocity, E/A ratio and E/e' ratio) were assessed using echocardiography. RVSP was significantly elevated in PAH subjects versus controls (57 ± 17 vs. 28 ± 8 mm Hg, P < 0.0001). CysC was abnormally elevated in the PAH cohort when compared with controls (1.00 ± 0.23 vs 0.78 ± 0.05 mg/L, P = 0.001). CysC positively correlated with RVSP (rho 0.61, P = 0.002), RV end-diastolic volume (rho 0.50, P = 0.01), RV end-systolic volume (rho 0.58, P = 0.003), mass index (rho 0.66, P = 0.0004), strain (rho 0.51, P = 0.01) and strain rate (rho 0.51, P = 0.01) and negatively correlated with RVEF (rho -0.58, P = 0.003) and TV e' (rho -0.75, P < 0.0001). The same correlations with BNP and NT-ProBNP were comparable with CysC. In a small cohort, CysC accurately correlates with RV pressure, function and morphology. CysC may represent a novel PAH biomarker. © 2014 Asian Pacific Society of Respirology.

  5. Serotonin 2B Receptor Antagonism Prevents Heritable Pulmonary Arterial Hypertension

    PubMed Central

    Schroer, Alison K.; Chen, Peter; Ryzhova, Larisa M.; Gladson, Santhi; Shay, Sheila; Hutcheson, Joshua D.; Merryman, W. David

    2016-01-01

    Serotonergic anorexigens are the primary pharmacologic risk factor associated with pulmonary arterial hypertension (PAH), and the resulting PAH is clinically indistinguishable from the heritable form of disease, associated with BMPR2 mutations. Both BMPR2 mutation and agonists to the serotonin receptor HTR2B have been shown to cause activation of SRC tyrosine kinase; conversely, antagonists to HTR2B inhibit SRC trafficking and downstream function. To test the hypothesis that a HTR2B antagonist can prevent BMRP2 mutation induced PAH by restricting aberrant SRC trafficking and downstream activity, we exposed BMPR2 mutant mice, which spontaneously develop PAH, to a HTR2B antagonist, SB204741, to block the SRC activation caused by BMPR2 mutation. SB204741 prevented the development of PAH in BMPR2 mutant mice, reduced recruitment of inflammatory cells to their lungs, and reduced muscularization of their blood vessels. By atomic force microscopy, we determined that BMPR2 mutant mice normally had a doubling of vessel stiffness, which was substantially normalized by HTR2B inhibition. SB204741 reduced SRC phosphorylation and downstream activity in BMPR2 mutant mice. Gene expression arrays indicate that the primary changes were in cytoskeletal and muscle contractility genes. These results were confirmed by gel contraction assays showing that HTR2B inhibition nearly normalizes the 400% increase in gel contraction normally seen in BMPR2 mutant smooth muscle cells. Heritable PAH results from increased SRC activation, cellular contraction, and vascular resistance, but antagonism of HTR2B prevents SRC phosphorylation, downstream activity, and PAH in BMPR2 mutant mice. PMID:26863209

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

    PubMed

    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. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

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

    PubMed

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

    2016-04-01

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

  8. Transient stenotic-like occlusions as a possible mechanism for renovascular hypertension due to aneurysm.

    PubMed

    Heflin, Linden A; Street, Carrie B; Papavassiliou, Dimitrios V; Kem, David C; Wu, Dee H; O'Rear, Edgar A

    2009-01-01

    The pathophysiologic basis of hypertension secondary to a renal artery aneurysm has not been established. Changes in renal artery geometry and resultant hemodynamic alterations activate the renin-angiotensin-aldosterone system and lead to hypertension. Hemodynamic pressure losses created by blood flowing through an abnormally structured renal artery with an aneurysm predictably would provoke a similar circumstance. The present study provides a hemodynamic rationale for this hypothesis. Using computational fluid dynamics, we have modeled renal flow for selected aneurysmal geometries. These studies reveal that pressure loss across the renal artery does not change ( approximately 0.9 mm Hg) significantly when a nondeformable aneurysm is interposed on the system. The calculations, however, demonstrate that the pressure on the aneurysm walls supports the presence of forces deforming and thereby obstructing the renal artery. A deformed wall was assumed and various degrees of occlusion were modeled. A partial occlusion of 60% resulted in a renal artery pressure loss of approximately 10 mm Hg. These simulations, when applied to aneurysms at various locations on the renal artery and with various degrees of occlusion, consistently resulted in pathologically relevant pressure losses. These findings lead to a new hypothesis of how aneurysms are associated with renovascular hypertension.

  9. [Effectiveness of primary health care in the diagnosis and treatment of arterial hypertension].

    PubMed

    Brugos Larumbe, A; Guillém, F; Díez, Javier; Buil, P; Ciáurriz, M; Fernández, C; Cenoz, J C

    2008-01-01

    Arterial hypertension (AHT) is a significant public health problem due to its high cardiovascular morbidity and mortality and its economic and social costs. Background. To identify the prevalence of AHT detected in primary care and its degree of control; to determine the types of treatment used and factors associated with its control. Patients and methods. Transversal comparative study of two years in the Villava Health Centre. The computerised clinical history data for the years 2003 and 2006 was analysed. The following variables were studied: age, gender, systolic and diastolic arterial pressure, total cholesterol, HDL, LDL, triglycerides, tobacco use, body mass index in both years. Hypotensor treatment in the year 2006. The variables for the year 2006 associated with good control were identified through logistic regression. Results. AHT prevalence detected in (3)18 year olds: 2003: 11.6% (CI:10.9-12.3); 2006: 16.6% (CI:15.8-17.4) (p<0.001). Control of hypertense persons with a register of arterial tension (AP:<140/90) in 2003: 45.1% (CI: 41.0-48.0) and in 2006: 40.4% (CI: 37.7-43.2) (p<0.05). Variables associated with good control: being male [OR 1.60 (IC: 1.26-2.03)] treatment with ARA II [OR 2.16 (CI: 1.50-3.09)] and being diabetic [OR 1.50 (CI: 1.10-2.03]. Associated with poor control: presenting cerebral vascular disease, peripheral vasculopathy and treatment with ACE inhibitors. Conclusions. A low prevalence of AHT was detected. The level of control was higher for the DAP than for the SAP. Treatment with AIIRA, being male and being diabetic were associated with a better control. Peripheral vasculopathy, ichaemic cardiopathy, cerebral vascular disease, ACE inhibitors use and age were associated with a poorer control.

  10. Intraoperative hypertensive crisis due to a catecholamine-secreting esthesioneuroblastoma

    PubMed Central

    Salmasi, Vafi; Schiavi, Adam; Binder, Zev A.; Ruzevick, Jacob; Orr, Brent A.; Burger, Peter C.; Ball, Douglas W.; Blitz, Ari M.; Koch, Wayne M.; Ishii, Masaru; Gallia, Gary L.

    2015-01-01

    Background Although uncommon, esthesioneuroblastomas may produce clinically significant amounts of catecholamines. Methods We report a patient with a catecholamine-secreting esthesioneuroblastoma who developed intraoperative hypertensive crisis. Results A patient with history of hypertension was referred to our skull base center for management of a residual esthesioneuroblastoma. A staged endonasal endoscopic approach was planned. At the conclusion of the first stage, a hypertensive crisis occurred. Work-up revealed elevated levels of serum and urinary catecholamines. The patient was treated with alpha adrenoceptor blockade prior to the second stage. Serum catecholamine levels following this second stage were normal. On immunohistochemical analysis, the tumor cells were found to be positive for tyrosine hydroxylase, the rate limiting enzyme in cathecholamine synthesis, and achaete-scute homologue 1, a transcription factor essential in the development of olfactory and sympathetic neurons. Conclusion Catecholamine production should be considered in the differential of unexpected extreme hypertension during surgical resection of esthesioneuroblastoma. PMID:25352487

  11. Acute hypertension activates mitogen-activated protein kinases in arterial wall.

    PubMed Central

    Xu, Q; Liu, Y; Gorospe, M; Udelsman, R; Holbrook, N J

    1996-01-01

    Mitogen-activated protein (MAP) kinases are rapidly activated in cells stimulated with various extracellular signals by dual phosphorylation of tyrosine and threonine residues. They are thought to play a pivotal role in transmitting transmembrane signals required for cell growth and differentiation. Herein we provide evidence that two distinct classes of MAP kinases, the extracellular signal-regulated kinases (ERK) and the c-Jun NH2-terminal kinases (JNK), are transiently activated in rat arteries (aorta, carotid and femoral arteries) in response to an acute elevation in blood pressure induced by either restraint or administration of hypertensive agents (i.e., phenylephrine and angiotensin II). Kinase activation is followed by an increase in c-fos and c-jun gene expression and enhanced activating protein 1 (AP-1) DNA-binding activity. Activation of ERK and JNK could contribute to smooth muscle cell hypertrophy/hyperplasia during arterial remodeling due to frequent and/or persistent elevations in blood pressure. PMID:8567974

  12. Adult Mouse Venous Hypertension Model: Common Carotid Artery to External Jugular Vein Anastomosis.

    PubMed Central

    Yang, Shun-Tai; Rodriguez-Hernandez, Ana; Walker, Espen J.; Young, William L.; Su, Hua; Lawton, Michael T.

    2015-01-01

    The understanding of the pathophysiology of brain arteriovenous malformations and arteriovenous fistulas has improved thanks to animal models. A rat model creating an artificial fistula between the common carotid artery (CCA) and the external jugular vein (EJV) has been widely described and proved technically feasible. This construct provokes a consistent cerebral venous hypertension (CVH), and therefore has helped studying the contribution of venous hypertension to formation, clinical symptoms, and prognosis of brain AVMs and dural AVFs. Equivalent mice models have been only scarcely described and have shown trouble with stenosis of the fistula. An established murine model would allow the study of not only pathophysiology but also potential genetic therapies for these cerebrovascular diseases. We present a model of arteriovenous fistula that produces a durable intracranial venous hypertension in the mouse. Microsurgical anastomosis of the murine CCA and EJV can be difficult due to diminutive anatomy and frequently result in a non-patent fistula. In this step-by-step protocol we address all the important challenges encountered during this procedure. Avoiding excessive retraction of the vein during the exposure, using 11-0 sutures instead of 10-0, and making a carefully planned end-to-side anastomosis are some of the critical steps. Although this method requires advanced microsurgical skills and a longer learning curve that the equivalent in the rat, it can be consistently developed. This novel model has been designed to integrate transgenic mouse techniques with a previously well-established experimental system that has proved useful to study brain AVMs and dural AVFs. By opening the possibility of using transgenic mice, a broader spectrum of valid models can be achieved and genetic treatments can also be tested. The experimental construct could also be further adapted to the study of other cerebrovascular diseases related with venous hypertension such as migraine

  13. [Arterial hypertension secondary to curable causes in adults].

    PubMed

    Plouin, P F; La Batide Alanore, A; Fiquet-Kempf, B; Rossignol, P; Launay-Mignot, P; Bobrie, G

    2002-03-02

    EXTENSIVE AND COSTLY INVESTIGATIONS: Are not warranted in the vast majority of hypertensive patients. Characteristics identifying the patients at risk for secondary hypertension can be used to define the small percentage of patients with hypertension who require more extensive diagnostic testing and management of their condition. Exposure to certain medicines, foods or drugs may cause reversible rises in blood pressure. Renovascular and adrenal diseases cause curable forms of hypertension. IN MANY CASES, THE PATIENT'S HISTORY: Examination and simple tests can detect such exposures and disorders. Checking for secondary hypertension is therefore an early step required for the management of all patients with hypertension, provided it is based on clinical signs and inexpensive tests. This primary screening cannot exclude the possibility of renovascular or adrenal disease in a small number of asymptomatic patients. The risk of missing a diagnosis is acceptable provided that blood pressure is normalized by non-specific antihypertensive treatment. However, more extensive etiologic investigation is required in patients who subsequently develop resistant hypertension. This secondary screening requires imaging and biochemical tests that are not required for primary screening. CORRECTION OF THE CAUSES: Of secondary forms of hypertension may restore blood pressure to normal. The patient's age affects the reversibility of renovascular and adrenal hypertension after etiologic treatment: the younger the patient, the higher the probability of blood pressure normalization.

  14. Patent foramen ovale in idiopathic pulmonary arterial hypertension: Long-term risk and morbidity.

    PubMed

    Gallo de Moraes, Alice; Vakil, Abhay; Moua, Teng

    2016-09-01

    Little is known about the presence of patent foramen ovale in idiopathic pulmonary arterial hypertension. While there is suspected worsening of hypoxemia confounding assessment and management of pulmonary hypertension, as well as possible increased morbidity from paradoxical emboli, there may be theoretical relief of worsening right-sided pressures by the same mechanism of right-to-left shunting. Retrospective review of consecutive patients diagnosed with idiopathic pulmonary arterial hypertension (WHO Group 1) via right heart catheterization, from 1998 to 2010. All patients also underwent a four chamber transthoracic echocardiogram with agitated saline contrast for the evaluation of patent foramen ovale. Primary clinical data was collected and compared between patients with and without patent foramen ovale along with univariable and multivariable predictors of long term survival. One hundred and fifty five patients were included in the study, 42 with patent foramen ovale (27%). Patients with patent foramen ovale were younger at pulmonary arterial hypertension diagnosis and trended towards higher right ventricular systolic pressures on echocardiography and mean pulmonary arterial pressures by right heart catheterization. Predictors of mortality included age, diffusing capacity for carbon monoxide, and severe hypoxemia. Only diffusing capacity and age were predictive of mortality after adjustment for a priori covariables. Patent foramen ovale is seen in a quarter of patients with idiopathic pulmonary arterial hypertension and associated with increased prevalence of severe hypoxemia but had no effect on long term survival. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Combining bosentan and sildenafil in pulmonary arterial hypertension patients failing monotherapy: real-world insights.

    PubMed

    Dardi, Fabio; Manes, Alessandra; Palazzini, Massimiliano; Bachetti, Cristina; Mazzanti, Gaia; Rinaldi, Andrea; Albini, Alessandra; Gotti, Enrico; Monti, Enrico; Bacchi Reggiani, Maria Letizia; Galiè, Nazzareno

    2015-08-01

    Pulmonary arterial hypertension is a severe disease with a complex pathogenesis, for which combination therapy is an attractive option.This study aimed to assess the impact of sequential combination therapy on both short-term responses and long-term outcomes in a real-world setting.Patients with idiopathic/heritable pulmonary arterial hypertension, or pulmonary arterial hypertension associated with congenital heart disease or connective tissue disease and who were not meeting treatment goals on either first-line bosentan or sildenafil monotherapy, were given additional sildenafil or bosentan and assessed after 3-4 months. Double combination therapy significantly improved clinical and haemodynamic parameters, independent of aetiology or the order of drug administration. Significant improvements in functional class were observed in patients with idiopathic/heritable pulmonary arterial hypertension. The 1-, 3- and 5-year overall survival estimates were 91%, 69% and 59%, respectively. Patients with pulmonary arterial hypertension associated with connective tissue disease had significantly poorer survival rates compared to other aetiologies (p<0.003).The favourable short-term haemodynamic results and good survival rates, observed in patients receiving both bosentan and sildenafil, supports the use of sequential combination therapy in patients failing on monotherapy in a real-world setting.

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

    PubMed

    Hoenecke, Johannes; Hartmann, Hans; Melk, Anette

    2015-08-01

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

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

    PubMed

    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.

  18. Altered structure of small cerebral arteries in patients with essential hypertension.

    PubMed

    Rizzoni, Damiano; De Ciuceis, Carolina; Porteri, Enzo; Paiardi, Silvia; Boari, Gianluca E M; Mortini, Pietro; Cornali, Claudio; Cenzato, Marco; Rodella, Luigi F; Borsani, Elisa; Rizzardi, Nicola; Platto, Caterina; Rezzani, Rita; Rosei, Enrico Agabiti

    2009-04-01

    Structural alterations in the microcirculation may be considered an important mechanism of organ damage. An increased media-to-lumen ratio of subcutaneous small resistance arteries has been demonstrated to predict the development of cardiocerebrovascular events in hypertensive patients. Alterations in the structure of small cerebral arteries have been demonstrated in animal models of experimental or genetic hypertension. However, no evaluation with reliable techniques has ever been performed in humans. Twenty-eight participants were included in the present study: they were 13 hypertensive patients and 15 normotensive individuals. All participants underwent a neurosurgical intervention for benign or malign tumors. A small portion of morphologically normal cerebral tissue was excised from surgical samples and examined. Cerebral small resistance arteries (relaxed diameter around 200 mum) were dissected and mounted on an isometric and isobaric myograph, and the tunica media to internal lumen ratio was measured. In addition, cerebral cortical microvessel density (MVD) was also evaluated. The tissue was sectioned and stained for CD31, and MVD was measured with an automated image analyzer (percentage of area stained). Blood pressure values were evaluated, before surgical intervention, by standard sphygmomanometry. M/L was significantly greater and MVD significantly lower in hypertensive patients than that in normotensive individuals. No difference between groups in collagen content or mechanical properties of cerebral small arteries was observed. Our results indicate that structural alterations of small cerebral vessels are present in hypertensive patients compared with normotensive individuals, similar to those previously observed in subcutaneous small arteries.

  19. Association of Brachial-Ankle Pulse Wave Velocity with Asymptomatic Intracranial Arterial Stenosis in Hypertension Patients.

    PubMed

    Wang, Yan; Zhang, Jin; Qain, Yuesheng; Tang, Xiaofeng; Ling, Huawei; Chen, Kemin; Li, Yan; Gao, Pingjin; Zhu, Dingliang

    2016-08-01

    Intracranial arterial stenosis is a common cause of ischemic stroke in Asians. We therefore sought to explore the relationship of brachial-ankle pulse wave velocity and intracranial arterial stenosis in 834 stroke-free hypertensive patients. Intracranial arterial stenosis was evaluated through computerized tomographic angiography. Brachial-ankle pulse wave velocity was measured by an automated cuff device. The top decile of brachial-ankle pulse wave velocity was significantly associated with intracranial arterial stenosis (P = .027, odds ratio = 1.82; 95% confidence interval: 1.07-3.10). The patients with the top decile of brachial-ankle pulse wave velocity showed 56% higher risk for the presence of intracranial arterial stenosis to the whole population, which was more significant in patients younger than 65 years old. We also found that brachial-ankle pulse wave velocity related to both intracranial arterial stenosis and homocysteine. Our study showed the association of brachial-ankle pulse wave velocity with asymptomatic intracranial arterial stenosis in hypertension patients, especially in relative younger subjects. Brachial-ankle pulse wave velocity might be a relatively simple and repeatable measurement to detect hypertension patients in high risk of intracranial arterial stenosis. Copyright © 2016. Published by Elsevier Inc.

  20. Changes in the pulmonary arteries of the rat during recovery from hypoxia-induced pulmonary hypertension.

    PubMed

    Hislop, A; Reid, L

    1977-12-01

    Pulmonary hypertension has been induced in rats by 2 weeks' exposure to hypoxia, equivalent to an altitude of approximately 5500 m, in a hypobaric chamber. The rats were removed from the chamber and allowed to recover for up to 8 weeks at atmospheric pressure. Precise quantitative microscopic techniques after injection of the pulmonary artery have been used to estimate the regression in the pulmonary artery of the structural changes associated with pulmonary hypertension. During recovery the degree of muscularization of the pulmonary arteries decreases by disappearance of muscle cells from the small arteries and a drop in arterial wall thickness of larger vessels. These changes do not seem to reflect pulmonary artery pressure directly, since right ventricular hypertrophy regresses at a faster rate. In hypertensive rats there is a "loss" of small arteries in the alveolar region and little filling of precapillary vessels. On recovery, some of the vessels fill, suggesting that encroachment on the lumen by muscle and endothelial cells has lessened. Even after 8 weeks' recovery, however, some arteries do not return, suggesting they have completely disappeared and that regions are left with relatively little perfusion. This reduction of vascular reserve presents without there being right ventricular hypertrophy.

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

    PubMed

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

    2013-01-01

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

  2. Breaking Down the Barriers: Why the Delay in Referral for Pulmonary Arterial Hypertension?

    PubMed Central

    Mandras, Stacy A.; Ventura, Hector O.; Corris, Paul A.

    2016-01-01

    Background: Pulmonary arterial hypertension (PAH) is a rare and fatal disease. While many treatment options have been shown to improve quality of life, exercise tolerance, and hemodynamics in PAH, survival remains poor, in part due to the advanced stage at which patients present to PAH specialists. Methods: This perspective paper explores challenges related to the timing of referral, diagnosis, and initiation of therapy. Results: Multiple factors account for the delay in referral, including fallacies in physician education, commercial influence resulting in inappropriate prescribing practices, and barriers in access to care. Conclusion: Improving physician education, encouraging the prescription of PAH medications to be done predominantly by PAH specialists, overcoming barriers to care, and promoting screening for PAH will help ensure early referral, diagnosis, and treatment. PMID:27660574

  3. Medical therapy for pulmonary arterial hypertension: updated ACCP evidence-based clinical practice guidelines.

    PubMed

    Badesch, David B; Abman, Steven H; Simonneau, Gerald; Rubin, Lewis J; McLaughlin, Vallerie V

    2007-06-01

    A consensus panel convened by the American College of Chest Physicians developed guidelines for the treatment of pulmonary arterial hypertension (PAH) that were published in 2004. Subsequently, several important clinical trials have been published, and new treatments have received regulatory approval. In addition, add-on and combination therapy are being explored, which promise to open new therapeutic avenues. This article, taking into consideration studies published prior to September 1, 2006, provides an update to the previously published guidelines. The original guidelines have been summarized, a discussion of new studies has been added, and the treatment algorithm has been revised to take into account recent developments in therapy. This update provides evidence-based treatment recommendations for physicians involved in the care of patients with PAH. Due to the complexity of the diagnostic evaluation required and the treatment options available, referral of patients with PAH to a specialized center continues to be strongly recommended.

  4. Medical therapy for pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines.

    PubMed

    Badesch, David B; Abman, Steve H; Ahearn, Gregory S; Barst, Robyn J; McCrory, Douglas C; Simonneau, Gerald; McLaughlin, Vallerie V

    2004-07-01

    Pulmonary arterial hypertension (PAH) is often difficult to diagnose and challenging to treat. Untreated, it is characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and death. The past decade has seen remarkable improvements in therapy, driven largely by the conduct of randomized controlled trials. Still, the selection of most appropriate therapy is complex, and requires familiarity with the disease process, evidence from treatment trials, complicated drug delivery systems, dosing regimens, side effects, and complications. This chapter will provide evidence-based treatment recommendations for physicians involved in the care of these complex patients. Due to the complexity of the diagnostic evaluation required, and the treatment options available, it is strongly recommended that consideration be given to referral of patients with PAH to a specialized center.

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

    PubMed Central

    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 solids – traditionally used by engineers in the design and virtual testing of complex metal and composite structures – applied to study the pulmonary vasculature, both in healthy and diseased states. In four subject areas, we briefly outline advances in computational methodology and provide examples of clinical relevance. PMID:21499523

  6. Peripheral and Cerebral Resistance Arteries in the Spontaneously Hypertensive Heart Failure Rat: Effects of Stilbenoid Polyphenols.

    PubMed

    Lee, Danielle I; Acosta, Crystal; Anderson, Christopher M; Anderson, Hope D

    2017-02-28

    Hypertension is associated with aberrant structure and mechanical properties of resistance arteries. We determined the effects of resveratrol, a non-flavonoid polyphenol found in foods such as red grapes, and structurally-similar analogues (pterostilbene and gnetol) on systolic blood pressure (SBP) and resistance arteries from the spontaneously hypertensive heart failure (SHHF) rat. SBP was elevated in 17-week-old SHHF vs. Sprague-Dawley rats (normotensive control; 194 ± 3 vs. 142 ± 6 mmHg, p < 0.01) and was unaffected by resveratrol, pterostilbene, or gnetol (2.5 mg/kg/d). Geometry and mechanical properties of pressurized mesenteric resistance arteries and middle cerebral arteries were calculated from media and lumen dimensions measured at incremental intraluminal pressures. SHHF arteries exhibited remodeling which consisted of augmented media-to-lumen ratios, and this was attenuated by stilbenoid treatment. Compliance was significantly reduced in SHHF middle cerebral arteries but not mesenteric arteries vis-à-vis increased wall component stiffness; stilbenoid treatment failed to normalize compliance and wall component stiffness. Our data suggest that neither AMPK nor ERK mediate stilbenoid effects. In conclusion, we observed arterial bed-specific abnormalities, where mesenteric resistance arteries exhibited remodeling and cerebral arteries exhibited remodeling and stiffening. Resveratrol, pterostilbene, and gnetol exhibited similar abilities to attenuate vascular alterations.

  7. Stiffening of the Extrapulmonary Arteries From Rats in Chronic Hypoxic Pulmonary Hypertension

    PubMed Central

    Drexler, E. S; Bischoff, J. E; Slifka, A. J; McCowan, C. N; Quinn, T. P; Shandas, R; Ivy, D. D; Stenmark, K. R

    2008-01-01

    Changes in the compliance properties of large blood vessels are critical determinants of ventricular afterload and ultimately dysfunction. Little is known of the mechanical properties of large vessels exhibiting pulmonary hypertension, particularly the trunk and right main artery. We initiated a study to investigate the influence of chronic hypoxic pulmonary hypertension on the mechanical properties of the extrapulmonary arteries of rats. One group of animals was housed at the equivalent of 5000 m elevation for three weeks and the other held at ambient conditions of ~1600 m. The two groups were matched in age and gender. The animals exposed to hypobaric hypoxia exhibited signs of pulmonary hypertension, as evidenced by an increase in the RV/(LV+S) heart weight ratio. The extrapulmonary arteries of the hypoxic animals were also thicker than those of the control population. Histological examination revealed increased thickness of the media and additional deposits of collagen in the adventitia. The mechanical properties of the trunk, and the right and left main pulmonary arteries were assessed; at a representative pressure (7 kPa), the two populations exhibited different quantities of stretch for each section. At higher pressures we noted less deformation among the arteries from hypoxic animals as compared with controls. A four-parameter constitutive model was employed to fit and analyze the data. We conclude that chronic hypoxic pulmonary hypertension is associated with a stiffening of all the extrapulmonary arteries. PMID:27096124

  8. Pulmonary artery dissection: an emerging cardiovascular complication in surviving patients with chronic pulmonary hypertension.

    PubMed

    Khattar, R S; Fox, D J; Alty, J E; Arora, A

    2005-02-01

    Pulmonary arterial dissection is an extremely rare and usually lethal complication of chronic pulmonary hypertension. The condition usually manifests as cardiogenic shock or sudden death and is therefore typically diagnosed at postmortem examination rather than during life. However, recent isolated reports have described pulmonary artery dissection in surviving patients. The first case of pulmonary artery dissection in a surviving patient with cor pulmonale caused by chronic obstructive pulmonary disease is presented. The aetiology, pathophysiology, and clinical presentation of pulmonary artery dissection are reviewed and factors that may aid diagnosis during life are discussed.

  9. Validation of impedance cardiography in pulmonary arterial hypertension.

    PubMed

    Panagiotou, Marios; Vogiatzis, Ioannis; Jayasekera, Geeshath; Louvaris, Zafeiris; Mackenzie, Alison; Mcglinchey, Neil; Baker, Julien S; Church, Alistair C; Peacock, Andrew J; Johnson, Martin K

    2017-02-06

    Non-invasive methods of measuring cardiac output are highly desirable in pulmonary arterial hypertension (PAH). We therefore sought to validate impedance cardiography (ICG) against thermodilution (TD) and cardiac magnetic resonance (CMR) in the measurement of cardiac output in patients under investigation for PAH. A prospective, cross-sectional study was performed to compare single-point measurements of cardiac output obtained by impedance cardiography (COICG ) technology (PhysioFlow(®) ) with (i) contemporaneous TD measurements (COTD ) at rest and steady-state exercise during right heart catheterization and (ii) CMR measurements (COCMR ) at rest obtained within 72 h. Paired COICG and COTD measurements were obtained in 25 subjects at rest and 16 subjects at exercise. COCMR measurements were obtained in 16 subjects at rest. There was unsatisfactory correlation and agreement between COICG and COTD at rest (r = 0·42, P = 0·035; bias: 1·21 l min(-1) , 95% CI: -2·33 to 4·75 l min(-1) ) and exercise (r = .65, P = .007; bias: 1·41 l min(-1) ; 95% CI: -3·99 to 6·81 l min(-1) ) and in the change in COICG and COTD from rest to exercise (r = 0·53, P = 0·033; bias: 0·76 l min(-1) , 95% CI: -3·74 to 5·26 l min(-1) ). There was also a lack of correlation and unsatisfactory agreement between resting COICG and COCMR (r = 0·38, P = 0·1; bias: 1·40 l min(-1) , 95% CI: -2·48 to 5·28 l min(-1) ). In contrast, there was close correlation and agreement between resting COTD and COCMR (r = 0·87, P<0·001; bias: -0·16 l min(-1) , 95% CI: -1·97 to 1·65). In a representative population of patients under investigation for PAH, ICG showed insufficient qualitative and quantitative value in the measurement of resting and exercise cardiac output when compared with TD and CMR. © 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  10. AMBITION: An important piece in the therapeutic puzzle of pulmonary arterial hypertension.

    PubMed

    Said, Karim

    2015-01-01

    It is believed that simultaneous targeting of two or more of the three pathogenic pathways of pulmonary arterial hypertension (the endothelin, nitric oxide, and prostacyclin pathways) is associated with additive or synergistic effects with subsequent increasing efficacy and improving outcomes. However, there is lack of evidence to guide the use of combination strategy among pulmonary arterial hypertension patients and many questions remain to be answered. One of these vital questions is whether the strategy of upfront initiation of combination therapy could improve patients outcomes compared to the strategy of initial monotherapy. The recently published AMBITION trial represents an important forward step towards answering this question by comparing a strategy of first-line combination therapy (ambrisentan and tadalafil) versus first-line monotherapy (ambrisentan or tadalafil) in patients with pulmonary arterial hypertension.

  11. Regression of small resistance artery structural alterations in hypertension by appropriate antihypertensive treatment.

    PubMed

    Agabiti-Rosei, Enrico; Rizzoni, Damiano

    2010-04-01

    Regardless of the mechanisms that initiate the rise of blood pressure, the development of structural changes in the systemic vasculature is the end result of established hypertension. Indices of small resistance artery structure, such as the ratio of tunica media to internal lumen, may have a strong prognostic significance in hypertensive patients, over and above all other known cardiovascular risk factors. Hence, the regression of vascular alterations seems to be an appealing goal for antihypertensive treatment. Different antihypertensive drugs may have different effects on vascular structure. Complete normalization of small resistance artery structure was demonstrated in hypertensive patients after long-term and effective antihypertensive therapy with angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and calcium antagonists. Little or no improvement was observed with beta-blockers or diuretics. Evidence from several studies suggests that some antihypertensive drugs are more effective than others in reversing microvascular structural alterations in hypertension.

  12. Bosentan for patients with echocardiographic evidence of pulmonary hypertension due to long-standing rheumatic mitral stenosis.

    PubMed

    Vlachogeorgos, Georgios S; Daskalopoulos, Nicholaos; Blatsiotis, Panayiotis; Kourbeti, Irene S; Mantas, Ioannis; Stathopoulos, Georgios T

    2015-01-01

    Vasoconstrictive endothelin signaling is not limited to idiopathic pulmonary arterial hypertension, but has also been implicated in pulmonary hypertension due to valvular heart disease. The efficacy and safety of endothelin receptor antagonists in these patients is unknown. We investigated the effects of bosentan in patients with transthoracic echocardiographic (TTE) evidence of pulmonary hypertension due to mitral stenosis associated with rheumatic fever. This was a prospective, single-center, open-label, uncontrolled study of bosentan in outpatients with uncorrected mitral stenosis due to rheumatic fever. The primary endpoint was exercise capacity at six months, as determined by six-minute walking distance (6MWD) and maximal oxygen uptake (VO₂max). Secondary endpoints were the BORG dyspnea index (BDI), echocardiographic left ventricular ejection fraction (LVEF) and pulmonary arterial pressure (PAP), serum pro-brain natriuretic peptide (proBNP), and adverse events at six months. Ten patients (eight females; mean age 75 years) were enrolled. Bosentan was well tolerated by nine, whereas one withdrew from treatment. By intention-to-treat analysis, bosentan resulted in a marked increase in 6MWD (+32 m, p=0.015), but a significant reduction in VO₂max (-0.45 mL/min/kg, p=0.011). Peak PAP did not change significantly, but mean PAP dropped by 16% (p=0.03) and LVEF increased by 6.5% (p=0.003). Profound reductions were observed in BDI and serum proBNP (-67% and -37%, p=0.002 and p=0.011, respectively). Adverse events included minor reductions in body mass and hematocrit. The results of this pilot study suggest that endothelin receptor antagonism improves the functional status of patients with TTE evidence of pulmonary hypertension due to valvular heart disease. Randomized controlled trials are needed to confirm the results.

  13. Tumor necrosis factor-α inhibition attenuates middle cerebral artery remodeling but increases cerebral ischemic damage in hypertensive rats.

    PubMed

    Pires, Paulo W; Girgla, Saavia S; Moreno, Guillermo; McClain, Jonathon L; Dorrance, Anne M

    2014-09-01

    Hypertension causes vascular inflammation evidenced by an increase in perivascular macrophages and proinflammatory cytokines in the arterial wall. Perivascular macrophage depletion reduced tumor necrosis factor (TNF)-α expression in cerebral arteries of hypertensive rats and attenuated inward remodeling, suggesting that TNF-α might play a role in the remodeling process. We hypothesized that TNF-α inhibition would improve middle cerebral artery (MCA) structure and reduce damage after cerebral ischemia in hypertensive rats. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were treated with the TNF-α inhibitor etanercept (ETN; 1.25 mg·kg(-1)·day(-1) ip daily) or PBS (equivolume) for 6 wk. The myogenic tone generation, postischemic dilation, and passive structure of MCAs were assessed by pressure myography. Cerebral ischemia was induced by MCA occlusion (MCAO). Myogenic tone was unchanged, but MCAs from SHRSP + ETN had larger passive lumen diameter and reduced wall thickness and wall-to-lumen ratio. Cerebral infarct size was increased in SHRSP + ETN after transient MCAO, despite an improvement in dilation of nonischemic MCA. The increase in infarct size was linked to a reduction in the number of microglia in the infarct core and upregulation of markers of classical macrophage/microglia polarization. There was no difference in infarct size after permanent MCAO or when untreated SHRSP subjected to transient MCAO were given ETN at reperfusion. Our data suggests that TNF-α inhibition attenuates hypertensive MCA remodeling but exacerbates cerebral damage following ischemia/reperfusion injury likely due to inhibition of the innate immune response of the brain.

  14. Exposure to Cigarette Smoke and the Carotid Arteries Calcification Index in Patients with Essential Hypertension.

    PubMed

    Gać, Paweł; Jaźwiec, Przemysław; Mazur, Grzegorz; Poręba, Rafał

    2017-07-01

    The arteries calcification index is a quantitative, mathematically estimated parameter characterizing the total amount of calcium within atherosclerotic plaques in the walls of arteries. The objective is to determine a relationship between exposure to cigarette smoke and the carotid arteries calcification index in patients with essential hypertension. The tested group included 66 patients with essential hypertension: 19 active smokers (subgroup A), 20 non-smokers, environmentally exposed to cigarette smoke (subgroup B) and 27 persons without exposure to cigarette smoke (subgroup C). The tested group was subjected to computed tomography angiography of carotid arteries. Evaluation of the carotid arteries calcification indexes was conducted. The average value of the total calcification index of the carotid arteries (CAci) amounted to 368.28 ± 384.21. In subgroup A and B in relation to subgroup C, CAci was significantly higher. In summary, active and passive smoking in patients with essential hypertension may be associated with a higher calcification index of carotid arteries.

  15. Arterial Resistance in Late First Trimester as a Predictor of Subsequent Pregnancy-Related Hypertension

    PubMed Central

    Kushtagi, Pralhad; Emani, Anoosha

    2016-01-01

    Objectives This study aimed to examine the association between indicators of arterial resistance occurring late in the first trimester and the subsequent development of pregnancy-related hypertension. Methods This study took place between May 2014 and August 2015 and included 329 consecutive women with singleton pregnancies attending the antenatal clinics of a medical college in Karnataka, India, during this period. Pulse pressure (PP) and uterine artery Doppler parameters were recorded between 11–14 gestational weeks. Consequently, women were followed-up until after delivery for subsequent hypertension. Results Hypertension occurred more frequently if PP was high (17.6% versus 14.4% of pregnancies without high PP; P = 0.713), if a diastolic notch (DN) was present (15.1% versus 12.8% of pregnancies with an absent DN; P = 0.612) and if the resistive index (RI) was raised (22.2% versus 14.3% of pregnancies without raised RI; P = 0.366). A raised pulsatility index (PI) was significantly associated with hypertension (P = 0.013). The risk of hypertension was approximately seven-fold higher if two or more arterial resistance indicators were used, except with a present DN plus a raised RI or a present DN plus high PP. All arterial resistance indicators showed negative predictability (>85.6%) and good specificity (≥95.0%), except for the presence of a DN. A population-specific cut-off PI value of 1.72 had high negative predictability (92.8%) and good sensitivity (70.8%) and specificity (65.1%). Conclusion Raised PI in the late first trimester was a significant predictor of hypertension later in pregnancy. A combination of arterial resistance indicators may enhance prediction of subsequent hypertension. PMID:28003891

  16. Prevalence of primary hyperaldosteronism in a systemic arterial hypertension league.

    PubMed

    Ribeiro, Maria Jacqueline Silva; Figueiredo Neto, José Albuquerque de; Memória, Edson Viriato; Lopes, Maíra de Castro; Faria, Manuel dos Santos; Salgado Filho, Natalino; Oliveira, Thiara Castro de

    2009-01-01

    Until recently, primary hyperaldosteronism was considered a rare cause of secondary hypertension. However, in recent years, many studies have suggested that this disease can affect up to 20% of hypertensive individuals. To determine the prevalence of primary hyperaldosteronism in hypertensive patients treated at the hypertension league of a university hospital. Serum aldosterone and plasma renin activity levels were measured in 105 patients while they were undergoing standard antihypertensive treatment, with the exception of those using betablockers and spironolactone, in fasting condition and after rest in the supine position for 20 minutes. Those with an aldosterone/plasma renin activity ratio > 25 were submitted to the saline suppression test and, after the confirmation of the autonomy of aldosterone secretion, a computed tomography of the adrenals was performed. The results are presented as percentages and means and standard deviations. Of the 105 patients, 6.54% presented refractory hypertension. Nine presented an aldosterone/plasma renin activity ratio > 25 (8.5% of the total). Of these, 08 were submitted to the saline suppression test and 01 (with refractory hypertension) had the diagnosis of primary hyperaldosteronism confirmed (0.96% of the total). A computed tomography of the adrenals was performed, which showed normal results. The prevalence of primary hyperaldosteronism in the studied sample was 0.96% of the total. However, when only the patients with refractory hypertension were evaluated, the prevalence was 14.3%.

  17. Application of speckle-tracking in the evaluation of carotid artery function in subjects with hypertension and diabetes.

    PubMed

    Yang, Eric Y; Brunner, Gerd; Dokainish, Hisham; Hartley, Craig J; Taffet, George; Lakkis, Nasser; Taylor, Addison A; Misra, Arunima; McCulloch, Marti L; Morrisett, Joel D; Virani, Salim S; Ballantyne, Christie M; Nagueh, Sherif F; Nambi, Vijay

    2013-08-01

    Speckle-tracking enables direct tracking of carotid arterial wall motion. Timing intervals determined with carotid speckle-tracking and slopes calculated from carotid artery area versus cardiac cycle curves may provide further information on arterial function and stiffness. The proposed arterial stiffness parameters were examined in healthy controls (n = 20), nondiabetic patients with hypertension (n = 20), and patients with type 2 diabetes (n = 21). Bilateral electrocardiographically gated ultrasonograms of the distal common carotid artery were acquired using a 12-MHz vascular probe. Four timing intervals were derived from speckle-tracked carotid arterial strain curves: (1) carotid predistension period, (2) peak carotid arterial strain time, (3) arterial distension period, and (4) arterial diastolic time. In addition, carotid artery area curves were recorded over the cardiac cycle and subdivided into four segments, S1 to S4, relating to arterial distention and contraction periods. Mean far wall predistension period and peak carotid arterial strain time were more delayed in patients with diabetes and hypertension than in controls. Global mean arterial distension period was prolonged and arterial diastolic time was shorter in patients with hypertension and diabetes than in controls. Slopes of segments S2 and S4 were markedly steeper in the combined group of patients with hypertension and diabetes compared with healthy controls (P = .03 and P = .02, respectively). Speckle-tracking-based measures of arterial stiffness may provide potential additive value in assessing vascular function in patients at risk for cardiovascular disease. Published by Mosby, Inc.

  18. Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension.

    PubMed

    Kossmann, Sabine; Lagrange, Jeremy; Jäckel, Sven; Jurk, Kerstin; Ehlken, Moritz; Schönfelder, Tanja; Weihert, Yvonne; Knorr, Maike; Brandt, Moritz; Xia, Ning; Li, Huige; Daiber, Andreas; Oelze, Matthias; Reinhardt, Christoph; Lackner, Karl; Gruber, Andras; Monia, Brett; Karbach, Susanne H; Walter, Ulrich; Ruggeri, Zaverio M; Renné, Thomas; Ruf, Wolfram; Münzel, Thomas; Wenzel, Philip

    2017-02-01

    Multicellular interactions of platelets, leukocytes, and the blood vessel wall support coagulation and precipitate arterial and venous thrombosis. High levels of angiotensin II cause arterial hypertension by a complex vascular inflammatory pathway that requires leukocyte recruitment and reactive oxygen species production and is followed by vascular dysfunction. We delineate a previously undescribed, proinflammatory coagulation-vascular circuit that is a major regulator of vascular tone, blood pressure, and endothelial function. In mice with angiotensin II-induced hypertension, tissue factor was up-regulated, as was thrombin-dependent endothelial cell vascular cellular adhesion molecule 1 expression and integrin αMβ2- and platelet-dependent leukocyte adhesion to arterial vessels. The resulting vascular inflammation and dysfunction was mediated by activation of thrombin-driven factor XI (FXI) feedback, independent of factor XII. The FXI receptor glycoprotein Ibα on platelets was required for this thrombin feedback activation in angiotensin II-infused mice. Inhibition of FXI synthesis with an antisense oligonucleotide was sufficient to prevent thrombin propagation on platelets, vascular leukocyte infiltration, angiotensin II-induced endothelial dysfunction, and arterial hypertension in mice and rats. Antisense oligonucleotide against FXI also reduced the increased blood pressure and attenuated vascular and kidney dysfunction in rats with established arterial hypertension. Further, platelet-localized thrombin generation was amplified in an FXI-dependent manner in patients with uncontrolled arterial hypertension, suggesting that platelet-localized thrombin generation may serve as an inflammatory marker of high blood pressure. Our results outline a coagulation-inflammation circuit that promotes vascular dysfunction, and highlight the possible utility of FXI-targeted anticoagulants in treating hypertension, beyond their application as antithrombotic agents in

  19. Health-related quality of life in patients with pulmonary arterial hypertension

    PubMed Central

    Taichman, Darren B; Shin, Jennifer; Hud, Laryssa; Archer-Chicko, Christine; Kaplan, Sandra; Sager, Jeffery S; Gallop, Robert; Christie, Jason; Hansen-Flaschen, John; Palevsky, Harold

    2005-01-01

    Background Improved outcomes with expanding treatment options for patients with pulmonary arterial hypertension present the opportunity to consider additional end-points in approaching therapy, including factors that influence health-related quality of life. However, comparatively little is known about health-related quality of life and its determinants in patients with pulmonary arterial hypertension. Methods Health-related quality of life was evaluated in a cross sectional study of 155 outpatients with pulmonary arterial hypertension using generic and respiratory-disease specific measurement tools. Most patients had either World Health Organization functional Class II or III symptoms. Demographic, hemodynamic and treatment variables were assessed for association with health-related quality of life scores. Results Patients with pulmonary arterial hypertension suffered severe impairments in both physical and emotional domains of health-related quality of life. Patients with idiopathic ("primary") pulmonary arterial hypertension had the best, and those with systemic sclerosis the worst health-related quality of life. Greater six-minute walk distance correlated with better health-related quality of life scores, as did functional Class II versus Class III symptoms. Hemodynamic measurements, however, did not correlate with health-related quality of life scores. No differences in health-related quality of life were found between patients who were being treated with calcium channel antagonists, bosentan or continuously infused epoprostenol at the time of quality of life assessment. Conclusion Health-related quality of life is severely impaired in patients with pulmonary arterial hypertension and is associated with measures of functional status. Specific associations with impaired health-related quality of life suggest potential areas for targeted intervention. PMID:16092961

  20. Acute hemodynamic effect of inhaled iloprost in pulmonary artery hypertension evaluated with echocardiography

    PubMed Central

    Loureiro, Maria José; Cotrim, Carlos; Simões, Otília; Miranda, Rita; Cordeiro, Pedro; Carrageta, Manuel

    2007-01-01

    Doppler echocardiography is useful in the initial evaluation and long-term follow-up of patients with pulmonary artery hypertension. Aerosolised iloprost has been shown to reduce pulmonary pressure immediately after inhalation. We report the echocardiographic findings in a patient with severe pulmonary hypertension, before and after the inhalation of aerosolized iloprost. These findings illustrate the acute influence of iloprost in right and left ventricular hemodynamics and morphology. These findings were reproduced in subsequent echocardiographic evaluations. PMID:18031578

  1. [The influence of citoflavin on molecular mechanisms of hypertensive encephalopathy development in patients with systolic arterial hypertension].

    PubMed

    Kartashova, E A; Romantsov, M G; Sarvilina, I V

    2014-01-01

    The molecular pharmacological effects of cytoflavin in patients with hypertensive encephalopathy (HE) and isolated systolic arterial hypertension (ISAH) have been investigated using the following methods: assessment of complaints, 24-hour arterial pressure monitoring, ultrasound diagnostics including echocardiography, measurement of lipid profiles and coagulograms, and molecular phenotyping by MALDI-TOF/TOF-MS. A combination of cytoflavin administration with standard therapy of HE and ISAH led to the most expressed return development of clinical symptoms, restoration of the hemodynamic, structural, and geometrical parameters of cardiovascular system, and normalization of the indices of lipid profiles and coagulograms in comparison to patients with HE and ISAH, which accepted only standard therapy. Molecular mechanisms of cytoflavin action have been revealed, which include control of the activity of cellular signaling pathways by means of intermolecular interactions. The optimized therapy of HE and ISAH is recommended for clinical application, which assumes a combined use of standard therapy and cytoflavin and provides a geroprotective action upon the cardiovascular system.

  2. [Arterial hypertension and sleep apnea hypopnea syndrome in primary care].

    PubMed

    Bayó Llibre, J; Riel Cabrera, R; Mellado Breña, E; Filomena Paci, J; Priego Artero, M; García Alfaro, F J; Grau Granero, J M; Vázquez González, D; López Solana, J; Fernández San Martín, M I

    2015-01-01

    Sleep apnea hypopnea syndrome (SAHS) is frequent in hypertensive patients and plays a role in a greater incidence of cardiovascular morbidity-mortality. This study aims to know the clinical profile of hypertensive patients with SAHS compared to hypertensive patients without SAHS to know which variables should be used to orient their screening from primary care. An observational, descriptive, retrospective study of cases (hypertensive patients with SAHS) and controls (hypertensive patients without) was performed in an urban health care center. Based on a computerized registry of the site, patients diagnosed of SAHS and hypertension over 30 years of age were selected. For each case, one control case of hypertensive patients without SAHS paired by age and gender was randomly obtained. A total of 64 cases and 64 controls were selected. Standing out in the bivariate analysis were greater BMI (34.3±12.8 vs. 28.6±3.6), predominance of obesity (70.3 vs. 35.9%), metabolic syndrome (77.3 vs. 42.2%), consumption of psychopharmaceuticals (19.7 vs. 7.8%) and anithypertensive drugs (26.5 vs. 14.0%), ischemic heart disease (20.3 vs. 9.4%) in the case group versus control group (P<.05 for all the variables). The multivariate analysis showed that only the presence of metabolic syndrome was related with the presence of SAHS in hypertensive patients (OR 4.65; 95% CI: 2.03-10.64; P<.001). Screening for SAHS should be performed in hypertensive patients seen in primary care if they have metabolic syndrome criteria. Copyright © 2014 SEHLELHA. Published by Elsevier Espana. All rights reserved.

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

    PubMed

    Bontemps, S; Pechère-Bertschi, A

    2015-09-09

    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.

  4. [Arterial hypertension at the time of diagnosis of type 2 diabetes in adults].

    PubMed

    Nibouche, W N; Biad, A

    2016-06-01

    Our aim was to determine the prevalence of arterial hypertension and evaluate its association with vascular chronic complications in newly diagnosed type 2 diabetes patients, in an observational, prospective study. We have recruited 327 newly diagnosed type 2 diabetics aged from 40 to 70 years, in general practice units. Arterial blood pressure has been measured according to WHO guidelines. All data on clinical examination, diabetes's chronic complications were collected during 6 months and statistically analyzed with Epi-Info 6.04 database program. Among the patients, 66.7% had arterial hypertension at diagnosis of diabetes, 28% were known as hypertensive. They were 54.3±8.4years old and have metabolic syndrome in 88.4%. Men have more frequently a higher cardiovascular risk, higher glycaemia and albuminuria; women were more likely to have a metabolic syndrome and a higher BMI. Blood pressure increases with cardiovascular risk and metabolic syndrome components. Microangiopathy is present in 65.7%, atherosclerosis in 59.4 and 71.2% of hypertensive patients who have atherosclerosis have also microvascular complications. The prevalence of arterial hypertension in newly diagnosed type 2 diabetes is high. This association is linked with an alarming level of vascular morbidity. Early detection and treatment of these two diseases need a better implication and motivation of patients and health care providers. Clinicaltrials.gov ID: NCT02002091. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

    PubMed

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

    2010-04-01

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

  6. [Analysis of changes in characteristics of arterial hypertension occupational risk in workers of nonferrous metallurgy].

    PubMed

    Vlasova, E M; Shliapnikov, D M; Lebedeva, T M

    2015-01-01

    The article covers changes in occupational cardiovascular risk for workers of nonferrous,metallurgy. Findings are that exposure to noise up to 94 dB with length of service increases possible atherosclerosis and metabolic syndrome. With 5 years of service, risk of the predicted conditions increases by 40.5%. When occupational exposure lasts over 5 years, risk of arterial hypertension increases. A group of workers without exposure to occupational factors appeared to have no connection between length of service and metabolic syndrome and arterial hypertension. Risk evolution modelling proved that risk of functional disorders in nonferrous metallurgy workers becomes unacceptable after 5 years of service (cardiovascular disorders are critical).

  7. [Influence of work intensity on development of arterial hypertension in metal-mining workers].

    PubMed

    Ustinova, O Iu; Alekseev, V B; Rumiantseva, A N; Orehova, Ia V

    2013-01-01

    The article covers data on influence of working shifts duration and shift work intensity on cardiovascular system functioning in operators of mining excavators. Findings are that 8 hours shift with regular shift schedule (40 working hours per week) gives significant load on cardiovascular system of workers engaged into underground activities. 50% of mining excavator operators following this working schedule develop transitory arterial hypertension within 10 years. Longer work shift over 8 hours and more intensive shifting schedule over 40 hours per week causes stable arterial hypertension within 3 months in 60% of workers, in 10% of cases associated with lower functioning of sinus node.

  8. Arterial hypertension with brachydactyly in a 15-year-old boy.

    PubMed

    Litwin, Mieczysław; Jurkiewicz, Elzbieta; Nowak, Katarzyna; Kościesza, Andrzej; Grenda, Ryszard; Malczyk, Katarzyna; Kościesza, Iwona

    2003-08-01

    Autosomal dominant brachydactyly with hypertension is the only form of monogenic hypertension which is not sodium dependent. The disease is characterized by brachydactyly type E, short stature, arterial hypertension and aberrant loop of posterior inferior cerebellar artery (PICA) causing neurovascular conflict. So far the syndrome was described in one family in Turkey and two in Canada. We report a case of a 15-year-old boy who was admitted because of arterial hypertension 160/100 mmHg. He complained also of attacks of bilateral numbness of hands with deterioration of visual field. Examination revealed short stature (156 cm) and bone deformities of hands and feet consistent with brachydactyly type E. Ophthalmoscopy showed mild narrowing of retinal arteries. Serum electrolytes, blood gases, and renal function were normal. Renin activity and aldosterone concentrations were raised, and 24-h urinary excretion of catecholamines and urinary steroid profile were in normal range. Renal Doppler ultrasound was normal, but renal scintigraphy suggested vascular changes in the left kidney. Echocardiographic examination, besides mild left ventricular hypertrophy, was normal. Magnetic resonance angiography (angio-MR) revealed bilateral abnormal PICA loops and neurovascular conflict. Spiral angiotomography of renal arteries revealed narrow additional left renal artery. Both nonconsanguineous parents and younger brother were healthy, with normal height, without bone deformities, and had normal intracranial vessels. Amlodipine and metoprolol were given, and blood pressure lowered to 143/87. Adding rilmenidine gave no effect and enalapril was then added. It led to further improvement in blood pressure control. To our knowledge, this is the first pediatric description of a sporadic form of autosomal dominant brachydactyly with hypertension with abnormalities of brain and renal arteries.

  9. Arterial hypertension in migraine: Role of familial history and cardiovascular phenotype.

    PubMed

    Babayan, Laura; Mamontov, Oleg V; Amelin, Alexander V; Bogachev, Mikhail; Kamshilin, Alexei A

    2017-03-01

    Recent studies indicate that migraine is associated with increased risk of cardiovascular diseases. However, links between autonomic cardiovascular regulation, arterial hypertension (AH) and migraine are still little explored. In this study, we evaluated autonomic regulation in migraine patients with and without hypertension. We studied 104 patients with migraine, aged 34±10 y, including 28 with and 76 without hypertension (M+AH and M-AH groups, respectively). The control group consisted of 88 healthy volunteers matched by age and sex. The autonomic regulation of circulation was examined with the tilt-table test, deep-breathing and Valsalva Maneuver, handgrip test, cold-stress induced vasoconstriction, arterial baroreflex, and blood pressure variability measurements. We found that migraine patients with concomitant hypertension demonstrated reduced arterial baroreflex, whereas other parameters of cardiac autonomic regulation were unchanged. In contrast, most indicators of vasomotor reactivity (blood pressure response to the hand-grip, Valsalva maneuver and cold vasoconstriction) were enhanced in migraine patients with no significant differences between migraine patients with and without hypertension. Patients from both M+AH and M-AH groups more commonly had a family history of cardiovascular disorders. Our data revealed increased vasomotor reactivity in migraine patients, with or without concomitant hypertension. This was associated with the family history of cardiovascular diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. [Arterial hypertension as a medical and social problem in the older urban population. The CINDI WHO Program study].

    PubMed

    Kaczmarczyk-Chałas, Krystyna; Kwaśniewska, Magdalena; Pikala, Małgorzata; Drygas, Wojciech

    2008-01-01

    Increasing lifespan and progressive aging of the Polish population results in rising demands on health care. Chronic diseases with a leading position of arterial hypertension (HA) prevail in morbidity rates of adult seniors. The aim of the study is to characterize hypertension in the elderly with regard to other risk factors, complications and therapeutic control. The study was carried out in 2002 within the framework of the CINDI WHO Programme. A total of 1460 persons were randomly selected among residents of Lodz aged > or = 65 years. The response rate was 57%. All participants underwent questionnaire interview, two blood pressure (BP) measurements, anthropometric and physical examination, ECG and laboratory tests. After final verification, we analysed data collected from 828 persons (289 men and 539 women). Mean values of systolic and diastolic BP were 147.6 and 83.6 mmHg, respectively. The increase of systolic BP with age of studied seniors was observed. Hypertension was diagnosed in 669 persons (79% men, 82% women). In most cases there were systolic-diastolic or isolated systolic hypertension. About 60% of seniors with elevated BP declared suffering from HA, while 73% were under antihypertensive treatment. Normalization of BP (< 140/ 90 mmHg) was achieved in 28% of treated patients. Most often prescribed medications were: ACE-inhibitors (51%), beta-blockers (40%), calcium channel blockers (31%) and diuretics (30%). Mean values of plasma lipids and prevalence of lipid disorders were comparable in hypertensive and normotensive persons. Among patients with HA there were significantly smaller percentage of smokers (8.6% vs 18.7%, p < 0.05). The prevalence of obesity, visceral obesity and metabolic syndrome was higher in hypertensive seniors. As a result, incidents of myocardial infarction and morbidity due to coronary artery disease were twice as cantly more often hospitalised and visited family doctors (7 vs 4.6 visits/year) in comparison to normotensive subjects.

  11. The effects of direct renin inhibitor, aliskiren, on arterial hypertension, chronic kidney disease and cardiovascular disease: optimal pharmacotherapy.

    PubMed

    Morishita, Yoshiyuki; Kusano, Eiji

    2013-03-01

    The renin-angiotensin-aldosterone system (RAAS) plays pivotal roles in the pathogenesis of progression of arterial hypertension, chronic kidney disease (CKD) and cardiovascular disease (CVD). Previous studies suggested that a direct renin inhibitor, aliskiren, may be effective for blood pressure lowering, renoprotection and cardiovascular protection. This review focuses on the effects of aliskiren for arterial hypertension, CKD and CVD.

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

    PubMed

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

    2016-05-06

    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 therapy (ECT) in a patient with IPAH. A 23-year-old woman with IPAH and type I diabetes mellitus (DM) presented with malignant catatonia. Her heart function was classified as New York Heart Association (NYHA) class III. She required a rapid cure and ECT due to various psychiatric symptoms resistant to conventional medications. Pulmonary hypertensive (PH) crisis is the most concerning complication that can be induced by the sympathetic stimulation of ECT. To avoid PH crisis, we administered oxygen using a laryngeal mask and administered remifentanil for anesthesia. We also prepared standby nitric oxide for possible PH crisis, although it was ultimately not needed. With 14 ECT sessions, her malignant catatonia was ameliorated without physical complications. ECT is an acceptable option for the treatment of medication-refractory psychiatric disturbances in patients with IPAH, provided careful management is assured to prevent or address complications.

  13. Sympathoexcitation and arterial hypertension associated with obstructive sleep apnea and cyclic intermittent hypoxia.

    PubMed

    Weiss, J Woodrow; Tamisier, Renaud; Liu, Yuzhen

    2015-12-15

    Obstructive sleep apnea (OSA) is characterized by repetitive episodes of upper airway obstruction during sleep. These obstructive episodes are characterized by cyclic intermittent hypoxia (CIH), by sleep fragmentation, and by hemodynamic instability, and they result in sustained sympathoexcitation and elevated arterial pressure that persist during waking, after restoration of normoxia. Early studies established that 1) CIH, rather than sleep disruption, accounts for the increase in arterial pressure; 2) the increase in arterial pressure is a consequence of the sympathoactivation; and 3) arterial hypertension after CIH exposure requires an intact peripheral chemoreflex. More recently, however, evidence has accumulated that sympathoactivation and hypertension after CIH are also dependent on altered central sympathoregulation. Furthermore, although many molecular pathways are activated in both the carotid chemoreceptor and in the central nervous system by CIH exposure, two specific neuromodulators-endothelin-1 and angiotensin II-appear to play crucial roles in mediating the sympathetic and hemodynamic response to intermittent hypoxia.

  14. Mathematical Model Analysis of Heart-Arterial Interaction in Hypertension

    DTIC Science & Technology

    2007-11-02

    in vivo data show that in hypertensives with LVH, systolic and diastolic blood pressure increase by about 40% while cardiac output is constant and wall...compliance 25% lower and peripheral resistance 40% higher in hypertensives than in normotensive controls [13], and predicted blood pressure , cardiac output...thickness increases by 30-55%. In both (i) and (ii), blood pressure increased by only 10% while cardiac output dropped by 20%. In (ii), LV wall

  15. Renal artery stenosis and hypertension after abdominal irradiation for Hodgkin disease. Successful treatment with nephrectomy

    SciTech Connect

    Salvi, S.; Green, D.M.; Brecher, M.L.; Magoos, I.; Gamboa, L.N.; Fisher, J.E.; Baliah, T.; Afshani, E.

    1983-06-01

    Hypertension secondary to stenosis of the left renal artery developed in a thirteen-year-old male six years after completion of inverted Y irradiation (3,600 rad) for abdominal Hodgkin disease. Surgical treatment with nephrectomy resulted in control of the hypertension without the use of antihypertensive agents. We review the literature for this unusual complication of abdominal irradiation, and recommend that a 99mTc-DMSA renal scan, selective renal vein sampling for renin determinations, and renal arteriography be performed on any patient in whom hypertension develops following abdominal irradiation in childhood.

  16. Dural arteriovenous fistulas as a cause of intracranial hypertension due to impairment of cranial venous outflow

    PubMed Central

    Cognard, C.; Casasco, A.; Toevi, M.; Houdart, E.; Chiras, J.; Merland, J.

    1998-01-01

    OBJECTIVES—A retrospective study was carried out on 13 patients with intracranial dural arteriovenous fistulas (DAVFs) who presented with isolated or associated signs of intracranial hypertension.
METHODS—Nine patients presented with symptoms of intracranial hypertension at the time of diagnosis. Ocular fundoscopy available in 12 patients showed bilateral papilloedema in eight and optic disk atrophy in four. Clinical evolution was particularly noticeable in five patients because of chronic (two patients) or acute (after lumbar shunting or puncture: three patients, one death) tonsillar herniation.
RESULTS—Two patients had a type I fistula (drainage into a sinus, with a normal antegrade flow direction). The remaining 11 had type II fistulas (drainage into a sinus, with abnormal retrograde venous drainage into sinuses or cortical veins). Stenosis or thrombosis of the sinus(es) distal to the fistula was present in five patients. The cerebral venous drainage was abnormal in all patients.
CONCLUSION—Type II (and some type I) DAVFs may present as isolated intracranial hypertension mimicking benign intracranial hypertension. Normal cerebral angiography should be added as a fifth criterion of benign intracranial hypertension. The cerebral venous drainage pattern must be carefully studied by contralateral carotid and vertebral artery injections to correctly evaluate the impairment of the cerebral venous outflow. Lumbar CSF diversion (puncture or shunting) may induce acute tonsillar herniation and should be avoided absolutely. DAVF may induce intracranial hypertension, which has a poor long term prognosis and may lead to an important loss of visual acuity and chronic tonsillar herniation. Consequently, patients with intracranial hypertension must be treated, even agressively, to obliterate the fistula or at least to reduce the arterial flow and to restore a normal cerebral venous drainage. The endovascular treatment may associate arterial or transvenous

  17. Transcatheter Embolization of Pulmonary Artery False Aneurysm Associated with Primary Pulmonary Hypertension

    SciTech Connect

    Hiraki, T. Kanazawa, S.; Mimura, H.; Yasui, K.; Okumura, Y.; Dendo, S.; Yoshimura, K.; Takahara, M.; Hiraki, Y.

    2004-03-15

    A 29-year-old woman with primary pulmonary hypertension presented with recurrent hemoptysis. Contrast-enhanced CT of the chest demonstrated the enhanced mass surrounded by consolidation related to parenchymal hemorrhage. Pulmonary angiography suggested that the mass was a pulmonary artery false aneurysm. After a microcatheter was superselectively inserted into the parent artery of the falseaneurysm, the false aneurysm was successfully treated by transcatheterembolization with coils. Her hemoptysis has never recurred.

  18. Effects of novel muscarinic M3 receptor ligand C1213 in pulmonary arterial hypertension models.

    PubMed

    Ahmed, Mohamed; VanPatten, Sonya; Lakshminrusimha, Satyan; Patel, Hardik; Coleman, Thomas R; Al-Abed, Yousef

    2016-12-01

    Pulmonary hypertension (PH) is a complex disease comprising a pathologic remodeling and thickening of the pulmonary vessels causing an after load on the right heart ventricle that can result in ventricular failure. Triggered by oxidative stress, episodes of hypoxia, and other undetermined causes, PH is associated with poor outcomes and a high rate of morbidity. In the neonate, this disease has a similar etiology but is further complicated by the transition to breathing after birth, which requires a reduction in vascular resistance. Persistent pulmonary hypertension of the newborn (PPHN) is one form of PH that is frequently unresponsive to current therapies including inhaled nitric oxide (due to lack of proper absorption and diffusion), and other therapeutics targeting signaling mediators in vascular endothelium and smooth muscle. The need for novel agents, which target distinct pathways in pulmonary hypertension, remains. Herein, we investigated the therapeutic effects of novel muscarinic receptor ligand C1213 in models of PH We demonstrated that via M3 muscarinic receptors, C1213 induced activating- eNOS phosphorylation (serine-1177), which is known to lead to nitric oxide (NO) production in endothelial cells. Using signaling pathway inhibitors, we discovered that AKT and calcium signaling contributed to eNOS phosphorylation induced by C1213. As expected for an eNOS-stimulating agent, in ex vivo and in vivo models, C1213 triggered pulmonary vasodilation and induced both pulmonary artery and systemic blood pressure reductions demonstrating its potential value in PH and PPHN In brief, this proof-of-concept study provides evidence that an M3 muscarinic receptor functionally selective ligand stimulates downstream pathways leading to antihypertensive effects using in vitro, ex vivo, and in vivo models of PH.

  19. Arterial switch operation with unidirectional valved patch closure of ventricular septal defect in patients with transposition of great arteries and severe pulmonary hypertension.

    PubMed

    Talwar, Sachin; Choudhary, Shiv Kumar; Nair, Vinitha Viswambharan; Chauhan, Sandeep; Kothari, Shyam Sunder; Juneja, Rajnish; Saxena, Anita; Airan, Balram

    2012-01-01

    For patients with dextro-transposition of great arteries (d-TGAs), ventricular septal defect (VSD), and severe pulmonary arterial hypertension (PAH), the common surgical options are palliative arterial switch operation (ASO) or palliative atrial switch operation leaving the VSD open. We evaluated the role of ASO with VSD closure using a fenestrated unidirectional valved patch (UVP). Between July 2009 and February 2011, six patients with TGAs, VSD, and severe PAH (mean age 39.8 ± 47.4 months, median 21, range 8-132 months), weighing 10.7 ± 9.2 kg (median 8.6, range 4.3-29 kg), underwent ASO with VSD closure using our simple technique of UVP. Mean pulmonary artery systolic pressure before the operation was 106 ± 12.7 mm Hg (median 107.5, range 95-126 mm Hg) and pulmonary vascular resistance was 9.5 ± 4.22 units (median 9.5, range 6.6-17.1 Wood units). There were no deaths. All patients had a postoperative systemic arterial saturation of more than 95%, although there were frequent episodes of systemic desaturation due to right-to-left shunt across the valved VSD patch (as seen on transesophageal and transthoracic echocardiograms). Mean follow-up was 10 ± 7.6 months (median 7.5, range 1-22 months). At most recent follow-up, all patients had systemic arterial saturation of more than 95% and no right-to-left shunt through the VSD patch. In one patient, the follow-up cardiac catheterization showed a fall in pulmonary artery systolic pressure to 49 mm Hg. Arterial switch operation with UVP VSD closure is feasible with acceptable early results. It avoids complications of palliative atrial switch (arrhythmia and baffle obstruction) and partially or completely open VSD.

  20. Hypertension increases the contractions to sumatriptan in the human internal mammary artery.

    PubMed

    Yildiz, O; Ciçek, S; Ay, I; Demirkiliç, U; Tuncer, M

    1996-11-01

    The internal mammary artery is the graft of choice for myocardial revascularization. The tendency to spasm increases toward the distal end of the internal mammary artery, which is the portion generally used for anastomosis. The distal internal mammary artery is more pharmacologically responsive to 5-hydroxytryptamine and several other vasoconstrictor agents than its midsection. We examined the effects of 5-hydroxytryptamine and a 5-hydroxytryptamine1-like receptor agonist sumatriptan on internal mammary artery segments (length, 3-4 mm) obtained from patients undergoing coronary artery bypass grafting. To unmask a 5-hydroxytryptamine1-like receptor-mediated contractile response, threshold concentrations of potassium chloride were used. 5-Hydroxytryptamine induced concentration-dependent contractions in all, quiescent and potassium chloride precontracted, preparations. Sumatriptan induced marked contraction in some of the quiescent internal mammary artery rings, whereas it elicited marked and concentration-dependent contractions in all of the preparations given a moderate tone by a threshold concentration of potassium chloride. The sensitivity to sumatriptan was higher in potassium chloride-precontracted distal arteries than it was for the quiescent distal segments. Additionally, the sensitivity to and the efficacy of sumatriptan were much more markedly potentiated by precontraction in the preparations taken from hypertensive patients. The more marked potentiation of the responses in arteries from hypertensive patients may be one of the factors influencing the patency rates.

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed Central

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

    2017-01-01

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

  4. Sudden death caused by unsuspected pulmonary arterial hypertension, 10 years after surgery for extrahepatic biliary atresia.

    PubMed

    Moscoso, G; Mieli-Vergani, G; Mowat, A P; Portmann, B

    1991-04-01

    A case of extrahepatic biliary atresia presenting with an acute respiratory episode and rapid deterioration, 10 years after a successful portoenterostomy and a very active life, was the setting of unsuspected severe pulmonary arterial hypertension leading to sudden death. The pulmonary arteries showed widespread plexiform lesions, thickening of the muscular media, and subendothelial proliferation. Occasionally, eccentric arterial obstructive lesions and fibrinous thrombi were observed. There was marked reduction of preacinar arterioles with a consequent increase in the alveolar/arterial ratio. The pulmonary veins showed arterialization of their walls. There was marked hypertrophy of myocardial fibres in the right ventricle together with foci of myocardial degeneration and fibrosis. Areas of endocardial thickening were observed in both ventricles. The absence of clinical indicators of pulmonary arterial hypertension at any but the terminal stages of the disease precluded any form of conservative management. Lung-heart and presumably liver transplantation might have been the only option. Prospective assessment of pulmonary function and haemodynamic studies should be considered in cirrhotic patients with portal hypertension.

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

    PubMed

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

    2014-02-01

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

  6. Resting arterial hypoxaemia in subjects with chronic heart failure, pulmonary hypertension and patent foramen ovale.

    PubMed

    Lovering, Andrew T; Lozo, Mislav; Barak, Otto; Davis, James T; Lojpur, Mihajlo; Lozo, Petar; Čaljkušić, Krešimir; Dujić, Željko

    2016-05-01

    What is the central question of this study? Does a patent foramen ovale contribute to resting arterial hypoxaemia, defined as arterial oxygen saturation <95%, in subjects with chronic heart failure with or without pulmonary arterial hypertension? What is the main finding and its importance? The presence of a patent foramen ovale contributed to resting arterial hypoxaemia only in subjects with chronic heart failure with pulmonary arterial hypertension. These data suggest that the presence of a patent foramen ovale should be considered in chronic heart failure patients with arterial hypoxaemia and pulmonary hypertension. The roles of intrapulmonary and intracardiac shunt in contributing to arterial hypoxaemia at rest in subjects with chronic heart failure (CHF) have not been well investigated. We hypothesized that blood flow through intrapulmonary arteriovenous anastomoses (Q̇ IPAVA ) and/or patent foramen ovale (Q̇ PFO ) could potentially contribute to arterial hypoxaemia and, with pulmonary hypertension (PH) secondary to CHF, this contribution may be exacerbated. Fifty-six subjects with CHF (New York Heart Association Classes I-III), with (+) or without (-) PH [defined as peak tricuspid regurgitation velocity ≥2.9 m s(-1) (CHF PH+, n = 32) and peak tricuspid regurgitation velocity ≤2.8 m s(-1) (CHF PH-, n = 24)], underwent arterial blood gas analysis and transthoracic saline contrast echocardiography concomitant with transcranial Doppler to detect Q̇ IPAVA and Q̇ PFO . Seventeen of 56 subjects with CHF (30%) had Q̇ PFO , but only four of 56 subjects with CHF had Q̇ IPAVA (7%), both similar to age- and sex-matched control subjects. Mean arterial oxygen saturation (SaO2) was lower in subjects with Q̇ PFO . Only CHF PH+ subjects with Q̇ PFO had arterial hypoxaemia (mean SaO2 <95%). Bubble scores assessed using transthoracic saline contrast echocardiography were correlated with microembolic signals detected with transcranial Doppler in subjects with

  7. [The rhythms of arterial pressure and heart rate in individuals with arterial hypertension under the conditions of Far North].

    PubMed

    Gapon, L I; Shurkevich, N P; Vetoshkin, A S; Gubin, D G

    2006-01-01

    The circadian and ultradian rhythms of blood pressure (BP) and heart rate (HR) were studied by means of 24-hour BP monitoring in patients with arterial hypertension (AH) and practically healthy people working in Far North shifts. The subjects were 418 men. The main group consisted of 177 men aged 18 to 59 working in trans-polar shifts in Yamburg, Tyumen region, latitude 57 North. The comparison group included 158 residents of a moderate climatic zone (Tyumen, latitude 57 North). The control group consisted of 83 practically healthy men, of whom 43 worked in Far North shifts, and 40 were residents of Tyumen. The groups were comparable by age, AH duration, and office systolic and diastolic BP (SBP; DBP). The study demonstrates that even healthy people working in Far North shifts display high BP variability and the decrease of the stability and power of SBP, DBP and HR circadian rhythms due to the reduction of the amplitude, contribution of the rhythm to the total variability, and the increase of the amplitude of high-frequency harmonics of the spectrum (a manifestation of extracircadian dissemination), which may be a sign of accelerated ageing and biological age increase, and may facilitate AH development. Development of AH under the extreme conditions of Far North shifts, unlike the conditions of moderate climatic zones, is accompanied by progressive BH variability increase, the worsening of the chronological structure of SBP and DBP, the increase of extracircadian dissemination, which can be of both clinical and prognostic significance.

  8. Strenuous Exercise Induced Syncope Due to Coronary Artery Anomaly

    PubMed Central

    Yavuz, Veysel; Cetin, Nurulah; Tuncer, Esref; Dalgic, Onur; Taskin, Ugur; Bilge, Ali Riza; Tikiz, Hakan

    2014-01-01

    Coronary artery anomalies are among the neglected topics in cardiology. Anomalous origin of the left main coronary artery from the right sinus of valsalva is a rare coronary anomaly observed in 0.15% of patients. During exercise, the distended aorta and pulmonary artery with increased blood flow may squeeze the Left Main Coronary Artery (LMCA) between them. Even though arrhythmias are common causes of syncope, one should also think about aberrant coronary artery in the patients with syncope of unexplained origin. Patients experiencing exercise induced syncope accompanied by symptoms of coronary ischemia (typically: chest pain, ischemic findings on ECG, and raised cardiac markers) should be referred to diagnostic coronary angiography. PMID:25177677

  9. Intrapulmonary arteries respond to serotonin and adenosine triphosphate in broiler chickens susceptible to idiopathic pulmonary arterial hypertension.

    PubMed

    Kluess, H A; Stafford, J; Evanson, K W; Stone, A J; Worley, J; Wideman, R F

    2012-06-01

    This study examined factors contributing to increased vascular resistance and plexiform lesion formation in broiler chickens susceptible to idiopathic pulmonary arterial hypertension (IPAH). A diet supplemented with excess tryptophan (high-Trp diet), the precursor for serotonin, was used to accelerate the development of IPAH. Broilers fed the high-Trp diet had higher pulmonary arterial pressures than broilers fed the control diet, and plexiform lesion incidences tended to be higher (P = 0.11) in the high-Trp group than in the control group at 30 d of age. The intrapulmonary arteries were assessed for vasoconstriction in response to serotonin and adenosine triphosphate (ATP) and for activities of key metabolic enzymes for serotonin and ATP. The pulmonary artery (defined as the first major branch of the pulmonary artery inside the lung) and the primary pulmonary arterial rami (defined as the second major branch of the pulmonary artery inside the lung) both exhibited vasoconstriction in response to serotonin and ATP. This is the first study to demonstrate purinergic-mediated vasoconstriction in intrapulmonary arteries from broilers. Arteriole responsiveness did not differ between broilers fed the control diet or the high-Trp diet. Therefore, the high-Trp diet enhanced the development of IPAH but did not affect the artery's sensitivity to serotonin or ATP. Monoamine oxidase activity, responsible for the breakdown of serotonin, was severely impaired in pulmonary arteries from broilers in the high-Trp group. Accordingly, serotonin may persist longer and elicit an amplified response in broilers fed the high-Trp diet.

  10. [Role of ophthalmoscopy in arterial hypertension: a problem revisited].

    PubMed

    Palatini, P; Penzo, M; Bongiovì, S; Canali, C; Pessina, A C

    1991-09-01

    To evaluate the present role of fundal examination in the assessment of the hypertensive patient, 348 hypertensive subjects, mostly with borderline or mild hypertension, were studied with direct ophthalmoscopy. The exam was always performed by the same observer. The degree of left ventricular hypertrophy was also evaluated with ECG and echocardiography. Blood pressure was measured with 24-hour ambulatory monitoring, using either the Del Mar Avionics Pressurometer II and IV, the Spacelabs 5200 or the A & D TM-2420. Signs of hypertensive retinopathy were found in 51% of the subjects. The degree of retinopathy, defined according to a modified Keith-Wagener grading system, was highly correlated with average 24-hour mean blood pressure (r = 0.31; p less than 0.0001). Based on ECG, 16% of the subjects had left ventricular hypertrophy, while 23% showed an echocardiographic left ventricular mass, indexed by body surface area, above the normal limits. Left ventricular mass index was correlated with ambulatory blood pressure levels, but at a lower level of statistical significance (r = 0.19; p less than 0.001) compared to the degree of retinopathy. No correlation was found between 24-hour blood pressure and ECG findings. Ophthalmoscopy proved to be more sensitive than echocardiography and ECG in indexing 24-hour blood pressure load, while the specificity of the 3 exams was similar. The present data indicate that fundal examination is a sensitive indicator of the vascular consequences of increased blood pressure and is therefore useful in the assessment of the hypertensive patient, while the more expensive echocardiography is not of great clinical value in borderline and mild hypertension.

  11. Aerobic exercise-related attenuation of arterial pulmonary hypertension: A right arrow targets the disease?

    PubMed

    Madonna, Rosalinda; De Caterina, Raffaele; Geng, Yong-Jian

    2016-12-01

    Characterized by progressive elevation of mean pulmonary artery pressure and pulmonary vascular resistance, pulmonary arterial hypertension (PAH) is an important health problem that contributes to right heart failure. Pulmonary arterial remodeling and constriction are two prominent features of PAH. It is a traditional view that increasing pulmonary blood flow and pressure, aerobic exercise does more harm than good to the pulmonary vasculature in PAH. However, recent studies have documented a potential benefit of low-intensity aerobic exercise for PAH patients. Here the current mini-review outlines the evidence and challenges for this additional tool in our armamentarium to combat this ominous disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Peripheral artery disease: a cause of refractory hypertension after renal transplantation.

    PubMed

    Dourado, Raquel; Gonçalves, Pedro de Araújo; Almeida, Manuel; Weigert, André; Bruges, Margarida; Gaspar, Augusta; Negrão, Acácio Pita; Machado, Domingos; Clemente, Belarmino; Teles, Rui; Machado, Francisco Pereira; Silva, Aniceto

    2008-03-01

    The authors report the case of a 44-year-old man, with a history of hypertension, smoking, peripheral artery disease and chronic renal failure. After renal transplantation, the patient developed persistent high blood pressure, despite optimal medical therapy. When angiotensin-converting enzyme (ACE) inhibitor therapy was begun, he developed acute anuric renal failure, which was reversed after interruption of the ACE inhibitor. After the initial clinical evaluation, the patient was referred for renal angiography, which revealed critical stenosis of the proximal left common iliac artery, just above the renal graft artery anastomosis. The patient underwent successful angioplasty and stenting of the lesion, with complete normalization of blood pressure.

  13. Effect of angiotensin II-induced arterial hypertension on the voltage-dependent contractions of mouse arteries.

    PubMed

    Fransen, Paul; Van Hove, Cor E; Leloup, Arthur J A; Schrijvers, Dorien M; De Meyer, Guido R Y; De Keulenaer, Gilles W

    2016-02-01

    Arterial hypertension (AHT) affects the voltage dependency of L-type Ca(2+) channels in cardiomyocytes. We analyzed the effect of angiotensin II (AngII)-induced AHT on L-type Ca(2+) channel-mediated isometric contractions in conduit arteries. AHT was induced in C57Bl6 mice with AngII-filled osmotic mini-pumps (4 weeks). Normotensive mice treated with saline-filled osmotic mini-pumps were used for comparison. Voltage-dependent contractions mediated by L-type Ca(2+) channels were studied in vaso-reactive studies in vitro in isolated aortic and femoral arteries by using extracellular K(+) concentration-response (KDR) experiments. In aortic segments, AngII-induced AHT significantly sensitized isometric contractions induced by elevated extracellular K(+) and depolarization. This sensitization was partly prevented by normalizing blood pressure with hydralazine, suggesting that it was caused by AHT rather than by direct AngII effects on aortic smooth muscle cells. The EC50 for extracellular K(+) obtained in vitro correlated significantly with the rise in arterial blood pressure induced by AngII in vivo. The AHT-induced sensitization persisted when aortic segments were exposed to levcromakalim or to inhibitors of basal nitric oxide release. Consistent with these observations, AngII-treatment also sensitized the vaso-relaxing effects of the L-type Ca(2+) channel blocker diltiazem during K(+)-induced contractions. Unlike aorta, AngII-treatment desensitized the isometric contractions to depolarization in femoral arteries pointing to vascular bed specific responses of arteries to hypertension. AHT affects the voltage-dependent L-type Ca(2+) channel-mediated contraction of conduit arteries. This effect may contribute to the decreased vascular compliance in AHT and explain the efficacy of Ca(2+) channel blockers to reduce vascular stiffness and central blood pressure in AHT.

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

    PubMed

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

    2014-02-01

    Physical activity has beneficial effects on arterial stiffness among healthy adults. There is a lack of data on this relationship in adults with hypertension. The majority of studies which have examined physical activity and arterial stiffness have used subjective measures of activity. The aim of this study was to investigate the relationship between objectively measured habitual physical activity and arterial stiffness in individuals with newly diagnosed essential hypertension. Adults attending an outpatient hypertension clinic were recruited into this cross sectional study. Physical activity was measured using a triaxial accelerometer. Pulse wave velocity (PWV) and augmentation index (AIx) were measured using applanation tonometry. Participant's full lipid profile and glucose were determined through the collection of a fasting blood sample. Fifty-three adults [51(14) years, 26 male] participated, 16 of whom had the metabolic syndrome. Inactivity was positively correlated with PWV (r = .53, P < .001) and AIx (r = .48, P < .001). There were significant inverse associations between habitual physical activity of all intensities and both AIx and PWV. In stepwise regression, after adjusting for potential confounders, physical activity was a significant predictor of AIx and PWV. Habitual physical activity of all intensities is associated with reduced arterial stiffness among adults with hypertension.

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

    PubMed

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

    2015-01-01

    Right ventricle ejection fraction (RVEF) evaluated with magnetic resonance imaging is a strong determinant of patient outcomes in pulmonary arterial hypertension. We evaluated the prognostic value of RVEF assessed with conventional planar equilibrium radionuclide angiography at baseline and change 3-6 months after initiating pulmonary arterial hypertension-specific therapy. In a prospective cohort of newly diagnosed patients with idiopathic, heritable or anorexigen-associated pulmonary arterial hypertension, RVEF was measured at baseline (n=100) and 3-6 months after initiation of therapy (n=78). After a median follow-up of 4.1 years, 41 deaths occurred, including 35 from cardiovascular causes. Patients with a (median) baseline RVEF >25% had better survival than those with a RVEF <25% using Kaplan-Meier analysis (p=0.010). RVEF at baseline was an independent predictor of all-cause and cardiovascular mortality in adjusted Cox regression model (p=0.002 and p=0.007, respectively; HR 0.93 for both). Patients with stable or increased RVEF at 3-6 months had a trend for improved all-cause survival (HR 2.43, p=0.086) and had less cardiovascular mortality (HR 3.25, p=0.034) than those in whom RVEF decreased despite therapy. RVEF assessed with conventional planar equilibrium radionuclide angiography at baseline and change in RVEF 3-6 months after therapy initiation independently predict outcomes in patients with pulmonary arterial hypertension.

  16. Endothelium-derived Relaxing Factors of Small Resistance Arteries in Hypertension

    PubMed Central

    2014-01-01

    Endothelium-derived relaxing factors (EDRFs), including nitric oxide (NO), prostacyclin (PGI2), and endothelium-derived hyperpolarizing factor (EDHF), play pivotal roles in regulating vascular tone. Reduced EDRFs cause impaired endothelium-dependent vasorelaxation, or endothelial dysfunction. Impaired endothelium-dependent vasorelaxation in response to acetylcholine (ACh) is consistently observed in conduit vessels in human patients and experimental animal models of hypertension. Because small resistance arteries are known to produce more than one type of EDRF, the mechanism(s) mediating endothelium-dependent vasorelaxation in small resistance arteries may be different from that observed in conduit vessels under hypertensive conditions, where vasorelaxation is mainly dependent on NO. EDHF has been described as one of the principal mediators of endothelium-dependent vasorelaxation in small resistance arteries in normotensive animals. Furthermore, EDHF appears to become the predominant endothelium-dependent vasorelaxation pathway when the endothelial NO synthase (NOS3)/NO pathway is absent, as in NOS3-knockout mice, whereas some studies have shown that the EDHF pathway is dysfunctional in experimental models of hypertension. This article reviews our current knowledge regarding EDRFs in small arteries under normotensive and hypertensive conditions. PMID:25343007

  17. Rate of decline of forced vital capacity predicts future arterial hypertension: the Coronary Artery Risk Development in Young Adults Study.

    PubMed

    Jacobs, David R; Yatsuya, Hiroshi; Hearst, Mary O; Thyagarajan, Bharat; Kalhan, Ravi; Rosenberg, Sharon; Smith, Lewis J; Barr, R Graham; Duprez, Daniel A

    2012-02-01

    Lung function studies in middle-aged subjects predict cardiovascular disease mortality. We studied whether greater loss of forced vital capacity (FVC) early in life predicted incident hypertension. The sample was 3205 black and white men and women in the Coronary Artery Risk Development in Young Adults Study examined between 1985 and 1986 (Coronary Artery Risk Development in Young Adults year 0, ages 18-30 years) and 2005-2006 and who were not hypertensive by year 10. FVC was assessed at years 0, 2, 5, 10, and 20. Proportional hazard ratios and linear regression models predicted incident hypertension at years 15 or 20 (n=508) from the change in FVC (FVC at year 10 - peak FVC, where peak FVC was estimated as the maximum across years 0, 2, 5, and 10). Covariates included demographics, center, systolic blood pressure, FVC maximum, smoking, physical activity, asthma, and body mass index. Unadjusted cumulative incident hypertension was 25% in the lowest FVC loss quartile (Q1; median loss: 370 mL) compared with 12% cumulative incident hypertension in those who achieved peak FVC at year 10 (Q4). Minimally adjusted hazard ratio for Q1 versus Q4 was 2.21 (95% CI: 1.73-2.83), and this association remained significant in the fully adjusted model (1.37; 95% CI: 1.05-1.80). Decline in FVC from average age at peak (29.4 years) to 35 years old predicted incident hypertension between average ages 35 and 45 years. The findings may represent a common pathway that may link low normal FVC to cardiovascular disease morbidity and mortality.

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

    PubMed Central

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

    2017-01-01

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

  19. Pulmonary hypertension in COPD: a review and consideration of the role of arterial vasodilators.

    PubMed

    Burger, Charles D

    2009-04-01

    The possibility that pulmonary hypertension (PH) may develop in patients with chronic obstructive pulmonary disease (COPD) is well established, but prevalence data vary. The current World Health Organization clinical classification includes COPD in diagnostic group III: PH associated with disorders of the respiratory system or hypoxemia. The National Institute of Health defines PH as a mean pulmonary artery pressure of greater than 25 mmHg. Approximately 10% of the patients seen over the last decade in the PH Clinic at Mayo Clinic in Jacksonville, Florida, have PH due to COPD. The pathophysiology is likely complex and involves hypoxic pulmonary vasoconstriction. Ultimately, chronic hypoxia results in vascular remodeling with narrowing of the vascular lumen. The right heart is forced to generate increased driving pressures to overcome the increased vascular resistance. As the disease progresses, cor pulmonale may develop. The mortality in this setting is increased with five-year survival of 20% to 36% and seems to correlate with worsening PH and age. Fortunately, the PH in most cases is mild and occurs primarily in those with severe hypoxemia. Only 1% to 4% of patients have PH seemingly out of proportion to the severity of the COPD. This disproportionate subgroup may represent an important phenotype that requires a different therapeutic approach. Although supplemental oxygen remains the primary treatment for all PH in association with chronic hypoxia, pulmonary arterial vasodilators may have a therapeutic role in this subgroup. Vasodilators may worsen gas exchange, however, and to date, have no proven benefit. Rigorous future study will be required to determine whether there is a role for using pulmonary arterial vasodilators in this setting.

  20. Simple renal cysts and arterial hypertension: does their evacuation decrease the blood pressure?

    PubMed

    Zerem, Enver; Imamović, Goran; Omerović, Safet

    2009-10-01

    To evaluate the relationships between simple renal cysts and arterial hypertension and whether their evacuation decreases the blood pressure (BP). In a cross-sectional design, we analyzed 184 study participants with cysts and compared hypertensive and nonhypertensive among them. Outcomes were the number, the size and the location of a cyst. In a cross-over design, we first evaluated the change in absolute value of SBP, DBP and mean BP in 62 hypertensive patients who underwent percutaneous evacuation of a cyst and then the decrease of BP as a categorical variable that comprised all study participants. There were 55% giant renal cysts among hypertensive and 24% among nonhypertensive patients (P = 0.0001). The prevalence rates of multiple and peripheral cysts in hypertensive and nonhypertensive patients were similar to those of single and perihilar cysts, respectively. Significant differences in SBP, DBP and mean BP were found between pretreatment readings and 3 days, 1 month, 3 months and 6 months after cyst evacuation (P < 0001). The differences were significant in all hypertensive patients (P < 0.001). There were less hypertensive patients 3 days after treatment than before treatment (P < 0.0001). An apparent association between the size of a simple renal cyst and hypertension was found, and aspiration of cysts resulted in a reduction of BP. Location and number of cysts were not related to BP.

  1. The Minimal Important Difference in Borg Dyspnea Score in Pulmonary Arterial Hypertension.

    PubMed

    Khair, Rubina M; Nwaneri, Chisom; Damico, Rachel L; Kolb, Todd; Hassoun, Paul M; Mathai, Stephen C

    2016-06-01

    Despite therapeutic advances, pulmonary arterial hypertension remains a disease without a cure. Focusing on symptoms, such as dyspnea, is an important part of assessing response to therapy. To determine the minimal important differences for the Borg dyspnea score and the Borg fatigue score in adult patients undergoing initial therapy for pulmonary arterial hypertension. We studied 129 patients enrolled between 2003 and 2013 in the Pulmonary Arterial Hypertension Program registry at Johns Hopkins University Hospital in Baltimore, Maryland. We analyzed baseline demographics, clinical characteristics, 6-minute-walk test distance, and Borg dyspnea and fatigue scores at baseline and at follow up 3 months after initiation of pulmonary arterial hypertension therapy. The minimal important differences for the Borg dyspnea and fatigue scores were determined using distributional and anchor-based methods, using 6-minute-walk test distance as the anchor. Most subjects were in New York Heart Association functional class II or III and had moderate to severe pulmonary arterial hypertension. The baseline Borg dyspnea score was 3.4 ± 1.9 units; the baseline Borg fatigue score was 2.8 ± 2.2 units. After therapy, the average change in the dyspnea score was -0.16 ± 1.9 units and the average change in the fatigue score was -0.21 ± 2.4 units. Using distributional methods, the minimum important difference for Borg dyspnea score ranged from 0.7 to 1.24 units and for Borg fatigue score ranged from 0.73 to 1.39 units. Using anchor-based methods, the minimum important difference for the Borg dyspnea scales was 0.36; this could not be calculated for the Borg fatigue score. Using distributional and anchor-based methods, we estimate the minimum important difference for Borg dyspnea scale in pulmonary arterial hypertension is approximately 0.9 units. Using distributional methods only, we estimate the minimum important difference for the Borg fatigue scale is around 1 unit

  2. Assessment of energy requirement for the retinal arterial network in normal and hypertensive subjects.

    PubMed

    Liu, D; Wood, N B; Witt, N; Hughes, A D; Thom, S A; Xu, X Y

    2012-01-01

    The retinal arterial network structure can be altered by systemic diseases such as hypertension and diabetes. In order to compare the energy requirement for maintaining retinal blood flow and vessel wall metabolism between normal and hypertensive subjects, 3D hypothetical models of a representative retinal arterial bifurcation were constructed based on topological features derived from retinal images. Computational analysis of blood flow was performed, which accounted for the non-Newtonian rheological properties of blood and peripheral vessel resistance. The results suggested that the rate of energy required to maintain the blood flow and wall metabolism is much lower for normal subjects than for hypertensives, with the latter requiring 49.2% more energy for an entire retinal arteriolar tree. Among the several morphological factors, length-to-diameter ratio was found to have the most significant influence on the overall energy requirement.

  3. [Microabluminuria in arterial hypertension. Measurement, variables, interpretation, recommendations].

    PubMed

    Hornych, A; Marre, M; Mimran, A; Chaignon, M; Asmar, R; Fauvel, J P

    2000-11-01

    Permanent hypertension is frequently associated with increased glomerular permeability to albumin at an early stage, indicating renal involvement and endothelial dysfunction. The definition of microalbuminuria is an urinary albumin excretion of 30-300 mg/24 hrs, confirmed on two occasions over a 3 month period. It may also be expressed in microgram/min, m/l or mg/mmol of creatinine. Radio-immunological, immunonephelometric methods and Elisa are specific and the most sensitive methods of measurement. There is a large intra-individual variability (25-60%) making it essential to repeat measurements always by the same technique. The prevalence of microalbuminuria is 5-8% in the general population and 6-24% in hypertensive patients. When present, it is a marker of increased cardiovascular risk. Clinical recommendations suggest adaptation of urinary collection according to the context: screening, diagnosis or clinical research. It is always necessary to start by dip-stick detection of proteinuria, haematuria or urinary infection. Clinical research requires repeated measurement of 24 hour microalbuminuria, sometimes divided into two periods of day and night, often associated with ambulatory blood pressure recordings and renal function tests. Studies of the effects of anti-hypertensive drugs on microalbuminuria could provide better evaluation. In conclusion, measurement of microalbuminuria remains a tool of clinical research allowing an assessment of cardiovascular and renal risk of hypertensive patients.

  4. Comprehensive analysis of myocardial infarction due to left circumflex artery occlusion: comparison with infarction due to right coronary artery and left anterior descending artery occlusion

    SciTech Connect

    Huey, B.L.; Beller, G.A.; Kaiser, D.L.; Gibson, R.S.

    1988-11-01

    Forty consecutive patients with creatine kinase-MB confirmed myocardial infarction due to circumflex artery occlusion (Group 1) were prospectively evaluated and compared with 107 patients with infarction due to right coronary artery occlusion (Group 2) and 94 with left anterior descending artery occlusion (Group 3). All 241 patients underwent exercise thallium-201 scintigraphy, radionuclide ventriculography, 24 h Holter electrocardiographic (ECG) monitoring and coronary arteriography before hospital discharge and were followed up for 39 +/- 18 months. There were no significant differences among the three infarct groups in age, gender, number of risk factors, prevalence and type of prior infarction, Norris index, Killip class and frequency of in-hospital complications. Acute ST segment elevation was present in only 48% of patients in Group 1 versus 71 and 72% in Groups 2 and 3, respectively (p = 0.012), and 38% of patients with a circumflex artery-related infarct had no significant ST changes (that is, elevation or depression) on admission (versus 21 and 20% for patients in Groups 2 and 3, respectively) (p = 0.001). Abnormal R waves in lead V1 were more common in Group 1 than in Group 2 (p less than 0.003) as was ST elevation in leads I, aVL and V4 to V6 (p less than or equal to 0.048). These differences in ECG findings between Group 1 and 2 patients correlated with a significantly higher prevalence of posterior and lateral wall asynergy in the group with a circumflex artery-related infarct. Infarct size based on peak creatine kinase levels and multiple radionuclide variables was intermediate in Group 1 compared with that in Group 2 (smallest) and Group 3 (largest). During long-term follow-up, the probability of recurrent cardiac events was similar in the three infarct groups.

  5. Evaluation of diet and nutritional status in patients aged 45+ with diagnosed, pharmacologically treated arterial hypertension

    PubMed Central

    Śmidowicz, Angelika; Suliburska, Joanna; Bogdanski, Paweł

    2014-01-01

    Introduction Diet plays a significant role in the prevention and treatment of arterial hypertension. Appropriate diet makes it possible to maintain adequate body weight and improve biochemical blood parameters. The aim of the study was to assess nutritional status of arterial hypertension patients in terms of their diet. Material and methods The study involved 55 patients diagnosed with arterial hypertension aged 45-70 years. Diet was evaluated using a 24-hour 7-day diet recall interview. In the course of the diet recall interview arterial pressure was measured three times at regular times, after a 15-minute rest period, and the recorded values were averaged. Nutritional status was assessed based on anthropometric measurements (height, body weight, waist circumference, hip circumference) and the resulting nutrition status indexes, i.e. BMI (body mass index), WHR (waist-hip ratio) as well as values of biochemical blood parameters. Conclusions It was found that a considerable proportion of patients are overweight or obese, have an inappropriate lipid profile and elevated blood glucose levels. Daily food rations (DFR) were inappropriately balanced. Daily food rations were deficient in energy, carbohydrates, dietary fibre, PUFA and folates. It was found that inadequate diet was correlated with nutritional status, lipid profile parameters and arterial blood pressure. PMID:26327839

  6. Evaluation of diet and nutritional status in patients aged 45+ with diagnosed, pharmacologically treated arterial hypertension.

    PubMed

    Reguła, Julita; Śmidowicz, Angelika; Suliburska, Joanna; Bogdanski, Paweł

    2014-05-01

    Diet plays a significant role in the prevention and treatment of arterial hypertension. Appropriate diet makes it possible to maintain adequate body weight and improve biochemical blood parameters. The aim of the study was to assess nutritional status of arterial hypertension patients in terms of their diet. The study involved 55 patients diagnosed with arterial hypertension aged 45-70 years. Diet was evaluated using a 24-hour 7-day diet recall interview. In the course of the diet recall interview arterial pressure was measured three times at regular times, after a 15-minute rest period, and the recorded values were averaged. Nutritional status was assessed based on anthropometric measurements (height, body weight, waist circumference, hip circumference) and the resulting nutrition status indexes, i.e. BMI (body mass index), WHR (waist-hip ratio) as well as values of biochemical blood parameters. It was found that a considerable proportion of patients are overweight or obese, have an inappropriate lipid profile and elevated blood glucose levels. Daily food rations (DFR) were inappropriately balanced. Daily food rations were deficient in energy, carbohydrates, dietary fibre, PUFA and folates. It was found that inadequate diet was correlated with nutritional status, lipid profile parameters and arterial blood pressure.

  7. Invited Commentary: Hypertension and Arterial Stiffness—Origins Remain a Dilemma

    PubMed Central

    Jacobs, David R.; Duprez, Daniel A.; Shimbo, Daichi

    2016-01-01

    In this issue of the Journal, Chen et al. (Am J Epidemiol. 2016;183(7):599–608) present repeated measures of aorto-femoral pulse wave velocity, capacitive compliance (C1), and oscillatory compliance (C2) in the Bogalusa Heart Study, with the purpose of addressing which comes first: blood pressure elevation or arterial stiffening. After an average follow-up period of 7 years (2000–2010), the authors found that blood pressure at a mean age of 36 years predicted change in arterial stiffening by a mean age of 43 years, but not the reverse. Essential hypertension results from a mosaic of pathological mechanisms. It has been theorized that biological pathways involving increased sympathetic tone, insulin resistance, renin-angiotensin-aldosterone activation, and inflammation lead to hyperkinetic circulation, volume overload, and vascular remodeling. The resultant accelerated vascular aging may be assessed by determining the degree of arterial stiffness. The findings of Chen et al. add important empirical information to the literature but do not solve the dilemma regarding the origins of essential hypertension, partly because there are many techniques for estimating the many aspects of arterial stiffness which are not fully understood. Mathematical features of estimates might not be uniform across the age range. There is a need for tracking blood pressure and different aspects of arterial stiffness from childhood onward, with an aim of preventing hypertension in adult life. PMID:26960705

  8. Hypertensive emergency presenting with an isolated celiac artery dissection: A rare case study.

    PubMed

    Swergold, Natalie; Kozusko, Steven; Rivera, Carlos; Sturt, Cindy

    2016-01-01

    To our knowledge the most recent article on celiac dissection was published in 2015 and reported 24 known cases of spontaneous isolated celiac trunk dissection [2]. While some of those cases reported hypertension as a risk factor, no other case presents as hypertensive emergency with an isolated celiac artery dissection. A 43 year-old man with a past medical history of uncontrolled hypertension, for which he had reportedly been non-compliant with follow-up, presented with complaints of severe, sudden-onset epigastric pain which was non-radiating and constant for 1 hour prior to arrival. On CT an intimal flap was noted within the celiac trunk, starting at the origin and extending into the left gastric, splenic, and the common hepatic arteries. The most common symptom in patients with celiac artery dissection is acute or chronic epigastric or abdominal pain [2,4,9,11]. The crux of the diagnosis of this condition relies on contrast enhanced CT. The superiority of the CT scan is because of the contrast tracking capability [11]. The two most common risk factors for celiac artery dissection are hypertension followed by vasculitis. Patients can be managed nonoperatively or with one of a few operative procedures. Conservative treatment consists of anticoagulants, antihypertensives, and antiplatelet therapy [2]. To the best of our knowledge, we present the 25th case of isolated celiac artery dissection. This is the first case of hypertensive emergency induced spontaneous isolated celiac trunk dissection in literature. Our patient was managed primarily with a labetalol drip. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    PubMed

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

    2011-01-01

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

  10. Pulmonary artery segmentation and quantification in sickle cell associated pulmonary hypertension

    NASA Astrophysics Data System (ADS)

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

    2008-03-01

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

  11. Renal artery stenosis: An unusual etiology of hypertensive encephalopathy in a child with fanconi anemia.

    PubMed

    Purkait, Radheshyam; Mukherji, Aritra; Datta, Sucharita; Bhadra, Ramchandra

    2015-01-01

    A 9-year-old girl, diagnosed case of Fanconi anemia, presented with generalized convulsion with altered sensorium. She had fever, severe pallor, sinus tachycardia, blood pressure of 180/120 mmHg in both upper and lower limb, pan-systolic murmur of grade 2/6, abdominal bruit and bilateral papilledema. A provisional diagnosis of hypertensive encephalopathy was made and managed with continuous labetalol infusion. Detailed evaluation including magnetic resonance angiography of renal artery detected underlying atrophic and non-functioning right kidney secondary to severe renal artery stenosis on the same side. She was started with multiple antihypertensives, but her blood pressure was maintained poorly. Later on, she underwent rightsided nephrectomy. Following surgery, she was doing well and maintaining normal blood pressure without any antihypertensives. Our child is the second reported case of Fanconi anemia associated with renal artery stenosis presenting with hypertensive encephalopathy.

  12. Prophylactic Pulmonary Artery Reduction in a Young Female with Severe Pulmonary Hypertension from Complete Atrioventricular Septal Defect

    PubMed Central

    Lee, Sun Hyang; Kwon, Bo Sang; Bae, Eun Jung; Noh, Chung Il; Kim, Woong Han

    2017-01-01

    Management of severely dilated pulmonary artery (PA) associated with severe pulmonary hypertension from congenital heart disease remains controversial, primarily due to its rare nature and concern for perioperative unpredictable complications. Herein, we report a 25 year-old female with a severely dilated PA (up to 73 mm), who was successfully treated by a PA graft replacement by creating a Y-shaped conduit using a 28 mm hemashield tube in the main PA and a 20 mm hemashield tube in both proximal parts of the branch PA. PMID:28154602

  13. Horner's syndrome and headache due to carotid artery disease.

    PubMed Central

    West, T E; Davies, R J; Kelly, R E

    1976-01-01

    Horner's syndrome was accompanied by ipsilateral pain in the head, face, or neck in eight patients. In all cases angiography showed narrowing of the internal carotid artery in a pattern compatible with dissection within the arterial wall. In one patient in whom this diagnosis was substantiated by surgical exploration biopsy of the arterial wall showed changes typical of cystic medial necrosis. It is suggested that this clinical presentation constitutes a distinct syndrome. Images FIG 1 FIG 2 PMID:1260349

  14. Endothelin ETB1 receptor agonism as a new therapeutic strategy in pulmonary arterial hypertension and chronic heart failure.

    PubMed

    Ramirez, Giuseppe A

    2013-11-01

    Pulmonary arterial hypertension and post-ischemic chronic heart failure are highly prevalent diseases with high morbidity and mortality rates due to chronic vascular injury and extensive remodeling responses at the level of the vessel walls. Endothelins play a central role in this setting, through a complex signaling system that mainly affects endothelial and vascular smooth muscle cells. ETA and ETB2 endothelin receptors are thought to mediate pro-ischemic responses, while ETB1 receptor activity could account for the overall protective effect of ETB signaling in physiology. The pharmacologic modulation of the endothelin system has mainly focused on the dual non-selective blockade of ETA and ETB endothelin receptors or to the selective blockade of ETA-related pathways to date. Good clinical results were achieved in the setting of pulmonary hypertension but no advantage has been demonstrated for heart failure. Restoring and enhancing the physiological protective role of ETB1-signaling with concomitant blockade of ETB2 could possibly improve the efficacy of current therapies in the setting of pulmonary arterial hypertension and post-ischemic chronic heart failure. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Potassium Channel Subfamily K Member 3 (KCNK3) Contributes to the Development of Pulmonary Arterial Hypertension.

    PubMed

    Antigny, Fabrice; Hautefort, Aurélie; Meloche, Jolyane; Belacel-Ouari, Milia; Manoury, Boris; Rucker-Martin, Catherine; Péchoux, Christine; Potus, François; Nadeau, Valérie; Tremblay, Eve; Ruffenach, Grégoire; Bourgeois, Alice; Dorfmüller, Peter; Breuils-Bonnet, Sandra; Fadel, Elie; Ranchoux, Benoît; Jourdon, Philippe; Girerd, Barbara; Montani, David; Provencher, Steeve; Bonnet, Sébastien; Simonneau, Gérald; Humbert, Marc; Perros, Frédéric

    2016-04-05

    Mutations in the KCNK3 gene have been identified in some patients suffering from heritable pulmonary arterial hypertension (PAH). KCNK3 encodes an outward rectifier K(+) channel, and each identified mutation leads to a loss of function. However, the pathophysiological role of potassium channel subfamily K member 3 (KCNK3) in PAH is unclear. We hypothesized that loss of function of KCNK3 is a hallmark of idiopathic and heritable PAH and contributes to dysfunction of pulmonary artery smooth muscle cells and pulmonary artery endothelial cells, leading to pulmonary artery remodeling: consequently, restoring KCNK3 function could alleviate experimental pulmonary hypertension (PH). We demonstrated that KCNK3 expression and function were reduced in human PAH and in monocrotaline-induced PH in rats. Using a patch-clamp technique in freshly isolated (not cultured) pulmonary artery smooth muscle cells and pulmonary artery endothelial cells, we found that KCNK3 current decreased progressively during the development of monocrotaline-induced PH and correlated with plasma-membrane depolarization. We demonstrated that KCNK3 modulated pulmonary arterial tone. Long-term inhibition of KCNK3 in rats induced distal neomuscularization and early hemodynamic signs of PH, which were related to exaggerated proliferation of pulmonary artery endothelial cells, pulmonary artery smooth muscle cell, adventitial fibroblasts, and pulmonary and systemic inflammation. Lastly, in vivo pharmacological activation of KCNK3 significantly reversed monocrotaline-induced PH in rats. In PAH and experimental PH, KCNK3 expression and activity are strongly reduced in pulmonary