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  1. Pulmonary arterial hypertension due to pulmonary vascular amyloid deposition in a patient with multiple myeloma

    PubMed Central

    Hashimoto, Hirotsugu; Kurata, Atsushi; Mizuno, Hideaki; Nashiro, Tamaki; Hangaishi, Akira; Kuroda, Masahiko; Usuki, Kensuke; Horiuchi, Hajime

    2015-01-01

    Systemic amyloidosis is characterized by amyloid deposition throughout the body and subsequent dysfunction of various organs. Although pulmonary amyloidosis does occur, pulmonary hypertension (PH) caused by amyloidosis is extremely rare. In most of these cases, amyloid deposition occurred diffusely in alveolar septa, indicating that PH was due to lung disease and/or hypoxia. On the other hand, the mechanism of PH due to amyloid deposition in the pulmonary arteries has never been demonstrated. Here, we report the first case of PH due to amyloid deposition in pulmonary elastic arteries and muscular artery, which was complicated by multiple myeloma (MM). In the autopsy specimen of the patient, amyloid deposition was found mainly in the pulmonary arterial media, along with intimal thickening with luminal narrowing. PH thus appeared to be caused by marked decrease of pulmonary elasticity due to the amyloid deposition in the arterial media that resulted in stasis of the blood flow and subsequent luminal narrowing. Our present data demonstrates a new concept of PH caused by amyloidosis, namely, pulmonary arterial hypertension due to amyloidosis. PMID:26823900

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

    PubMed

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

    2006-08-01

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

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

    PubMed Central

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

    2014-01-01

    Idiopathic Pulmonary Hypertension (IPAH) is characterized by elevated pulmonary arterial pressure in the absence of an identifiable underlying cause. The condition is usually relentlessly progressive with a short survival in the absence of treatment.1 We describe a patient of IPAH in whom the pulmonary artery pressures significantly abated with complete disappearance of symptoms, following spontaneous development of a pulmonary arterio-venous malformation (PAVM). PMID:25443608

  4. 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. PMID:25490411

  5. 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

  6. Arterial hypertension and cancer.

    PubMed

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

    2014-05-15

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

  7. 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.

  8. 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

  9. 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

    2013-01-01

    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

  10. [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.

  11. The kidney and arterial hypertension.

    PubMed

    Ruilope, L M; Campo, C; Lahera, V

    1993-01-01

    It has been known for some time that a relationship exists between the kidney and blood pressure. The renal origin of arterial hypertension has been demonstrated in different animal models resembling human hypertension, with data from humans seeming to confirm this hypothesis. On the other hand, the renal vasculature also suffers the consequences of arterial hypertension, and renal insufficiency can develop as a result of elevated blood pressure levels. Antihypertensive therapy can prevent the development of renal damage secondary to hypertension. For example, calcium antagonists possess specific renal effects that not only facilitate their antihypertensive capacity but also protect the kidney from the development of renal failure.

  12. Pulmonary Arterial Hypertension

    MedlinePlus

    ... What Is Pulmonary Hypertension? To understand pulmonary hypertension (PH) it helps to understand how blood ows throughout ... is too high, it is called pulmonary hypertension (PH). How the pressure in the right side of ...

  13. Renal implications of arterial hypertension.

    PubMed

    Ruilope, L M

    1997-03-01

    Renal vascular damage caused by arterial hypertension participates in alterations of the systemic vascular function and structure. Nephrosclerosis seems to run in parallel with the systemic atherosclerosis that accounts for the increased cardiovascular morbidity and mortality seen in hypertensive patients. Parameters indicating the existence of an alteration in renal function (increased serum creatinine, proteinuria and microalbuminuria) are independent predictors for an increased cardiovascular morbidity and mortality. Hence, parameters of renal function must be considered in any stratification of cardiovascular risk in hypertensive patients.

  14. Immune Mechanisms in Arterial Hypertension.

    PubMed

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

    2016-03-01

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

  15. [Differential diagnosis of secondary arterial hypertension].

    PubMed

    Ruilope, L M

    1990-01-01

    The adequate performance of the differential diagnosis will permit us to classify any increase in blood pressure as due to primary or secondary causes. The data obtained in the clinical history and physical examination as well as those obtained through the minimal laboratory tests to be performed are the clues to identify secondary causes of arterial hypertension.

  16. Secondary arterial hypertension linked to Freon exposure.

    PubMed

    Voge, V M

    1996-05-01

    Freons are generally considered to be minimally toxic. There are no reports in the literature of Freons causing secondary arterial hypertension. We report two cases of acute, massive Freon exposure that preceded secondary arterial hypertension. We hypothesize that the arterial hypertension was precipitated by renal proximal tubular damage, although several other mechanisms are possible.

  17. [PREDICTORS OF RESISTANT ARTERIAL HYPERTENSION].

    PubMed

    Lazutkina, A Y; Gorbunov, V V

    2016-01-01

    The paper reports results of 6 year prospective observation of 7959 members of locomotive crews engaged at the Transbaikal Railways. The study aimed to estimate the probability and time of development of resistant arterial hypertension under effect of predictors of this disease. The data obtained are of value for diagnostic, prophylactic, and therapeutic practice. PMID:27522725

  18. [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.

  19. [Arterial hypertension and metabolic syndrome].

    PubMed

    Christ, Michael; Klima, Theresia; Maisch, Bernhard

    2003-12-01

    BACKGROUND AND THERAPY: The metabolic syndrome comprises a virulent and lethal group of atherosclerotic risk factors, including dyslipidemia, obesity, systemic hypertension and insulin resistance. The prevalence of the metabolic syndrome has continuously grown in industrialized and developing countries during the last decades, and affects tens of millions of people in Germany and Europe. Particularly prominent as a risk factor for the development of insulin resistance is central obesity, which is causally involved in the pathogenesis of insulin resistance in addition to genetic predisposition. The metabolic syndrome can easily be diagnosed in clinical practice (guidelines of the WHO and ATP III panel), and immediate treatment of the metabolic syndrome is mandatory because those patients are at increased risk to develop overt diabetes mellitus, coronary artery disease and stroke. The high risk for cardiovascular diseases is supported by findings that the risk for myocardial infarction in patients with insulin resistance is as high as the risk of patients after their first myocardial infarction. Intentional weight reduction reduces abdominal obesity and beneficially modulates all features of the metabolic syndrome, while the benefits of aerobic exercise training are discussed controversially. Thus, weight reduction causally undoes essential features of the metabolic syndrome, but effects are often not enduring. Therefore, the treatment of cardiovascular risk factors such as hypertension and dislipidemia is essential. Of note, antihypertensive treatment is more effective than tight glucose control to reduce cardiovascular events. Diuretics, ACE-inhibitors and angiotensin II type 1 receptor antagonists are suggested as first line therapeutics. However, at least two antihypertensives are usually necessary to achieve the suggested goals of blood pressure reduction. In conclusion, the prevalence of the metabolic syndrome is continuously growing. Due to its adverse impact

  20. 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. PMID:26730462

  1. 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.

  2. [Update arterial hypertension 2015].

    PubMed

    Rickenbacher, Peter

    2015-04-22

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

  3. Pulmonary arterial hypertension and pregnancy

    PubMed Central

    Terek, Demet; Kayikcioglu, Meral; Kultursay, Hakan; Ergenoglu, Mete; Yalaz, Mehmet; Musayev, Oktay; Mogulkoc, Nesrin; Gunusen, Ilkben; Akisu, Mete; Kultursay, Nilgun

    2013-01-01

    This is the case report of a pregnant woman who refused pregnancy termination when diagnosed with pulmonary arterial hypertension (PAH) functional class 2–3 at the 24th week of gestation and of her newborn. A pregnant woman with PAH functional class 2–3 was treated with inhaled prostacyclin analog (iloprost), oral sildenafil, oxygen, and low molecular weight heparin. She delivered at 32nd week by Cesarean section. The infant required oxygen up to 36th week postconceptional age and had a short steroid treatment. The mother needed close cardiovascular monitorization, intensive oxygen and pulmonary vasodilator therapy for 2 months and was discharged with oxygen and oral iloprost treatment. A multidisciplinary approach together with pulmonary vasodilator therapy may be succesful in such a high-risk pregnant woman. PMID:23900530

  4. [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.

  5. Exercise physiology and pulmonary arterial hypertension.

    PubMed

    Waxman, Aaron B

    2012-01-01

    The lungs are the only organ that receives the entire cardiac output with every stroke. The pulmonary circulation is normally a high-flow, low-resistance, low-pressure system that carries blood into the pulmonary microcirculation. In pulmonary artery hypertension (PAH)vascular remodeling contributes to a sustained elevation of pulmonary vascular resistance (PVR) and pulmonary artery pressure (PAP) as a result of vascular remodeling characterized largely by vascular smooth muscle cell proliferation and medial hypertrophy, and endothelial cell proliferation resulting in lumen obliteration. The loss of pulmonary arterial compliance and development of elevated PVR puts an excessive burden on the right ventricle due to the increased workload necessary to overcome the downstream pressure, ultimately leading to right-sided heart failure. The functional status of the pulmonary circulation and the levels of PVR and PAP ultimately determine the outcome of patients with PAH. Study of the pressure-flow relationships in the pulmonary vascular bed will provide an improved appreciation of the pathophysiology of pulmonary hypertension.

  6. Definition, classification, and epidemiology of pulmonary arterial hypertension.

    PubMed

    Hoeper, Marius M

    2009-08-01

    Pulmonary arterial hypertension (PAH) is a distinct subgroup of pulmonary hypertension that comprises idiopathic PAH, familial/heritable forms, and PAH associated with connective tissue disease, congenital heart disease, portal hypertension, human immunodeficiency virus (HIV) infection, and some other conditions. The hemodynamic definition of PAH was recently revised: PAH is now defined by a mean pulmonary artery pressure at rest > or =25 mm Hg in the presence of a pulmonary capillary wedge pressure < or =15 mm Hg. The exercise criterion (mean pulmonary artery pressure > or =30 mm Hg during exercise) that was used in the old definition of PAH has been removed because there are no robust data that would allow defining an upper limit of normal for the pulmonary pressure during exercise. The revised classification of pulmonary hypertension still consists of five major groups: (1) PAH, (2) pulmonary hypertension due to left heart disease, (3) pulmonary hypertension due to chronic lung disease and/or hypoxia, (4) chronic thromboembolic pulmonary hypertension, and (5) miscellaneous forms. Modifications have been made in some of these groups, such as the addition of schistosomiasis-related pulmonary hypertension and pulmonary hypertension in patients with chronic hemolytic anemia to group 1.

  7. Inflammation in pulmonary arterial hypertension.

    PubMed

    Price, Laura C; Wort, S John; Perros, Frédéric; Dorfmüller, Peter; Huertas, Alice; Montani, David; Cohen-Kaminsky, Sylvia; Humbert, Marc

    2012-01-01

    Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling of the precapillary pulmonary arteries, with excessive proliferation of vascular cells. Although the exact pathophysiology remains unknown, there is increasing evidence to suggest an important role for inflammation. Firstly, pathologic specimens from patients with PAH reveal an accumulation of perivascular inflammatory cells, including macrophages, dendritic cells, T and B lymphocytes, and mast cells. Secondly, circulating levels of certain cytokines and chemokines are elevated, and these may correlate with a worse clinical outcome. Thirdly, certain inflammatory conditions such as connective tissue diseases are associated with an increased incidence of PAH. Finally, treatment of the underlying inflammatory condition may alleviate the associated PAH. Underlying pathologic mechanisms are likely to be "multihit" and complex. For instance, the inflammatory response may be regulated by bone morphogenetic protein receptor type 2 (BMPR II) status, and, in turn, BMPR II expression can be altered by certain cytokines. Although antiinflammatory therapies have been effective in certain connective-tissue-disease-associated PAH, this approach is untested in idiopathic PAH (iPAH). The potential benefit of antiinflammatory therapies in iPAH is of importance and requires further study. PMID:22215829

  8. Drugs induced pulmonary arterial hypertension.

    PubMed

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

    2013-09-01

    Pulmonary arterial hypertension (PAH) is a rare disorder characterized by progressive obliteration of the pulmonary microvasculature, resulting in elevated pulmonary vascular resistance and premature death. According to the current classification, PAH can be associated with exposure to certain drugs or toxins, particularly appetite suppressant drugs, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market. The supposed mechanism is an increase in serotonin levels, which was demonstrated to act as a growth factor for the pulmonary arterial smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used but are also considered as possible risk factors for PAH. Dasatinib, a dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, in part reversible after its withdrawal. Recently several studies raised the potential endothelial dysfunction that could be induced by interferon, and few cases of PAH have been reported with interferon therapy. Other possible risk factors for PAH include: nasal decongestants, like phenylpropanolamine, dietary supplement - L-Tryptophan, selective serotonin reuptake inhibitors, pergolide and other drugs that could act on 5HT2B receptors. Interestingly, PAH remains a rare complication of these drugs, suggesting possible individual susceptibility and further studies are needed to identify patients at risk of drugs induced PAH. PMID:23972547

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

    PubMed

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

    2014-05-14

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

  10. Pulmonary hypertension and pulmonary artery dissection

    PubMed Central

    Corrêa, Ricardo de Amorim; Silva, Luciana Cristina dos Santos; Rezende, Cláudia Juliana; Bernardes, Rodrigo Castro; Prata, Tarciane Aline; Silva, Henrique Lima

    2013-01-01

    Pulmonary artery dissection is a fatal complication of long-standing pulmonary hypertension, manifesting as acute, stabbing chest pain, progressive dyspnea, cardiogenic shock, or sudden death. Its incidence has been underestimated, and therapeutic options are still scarce. In patients with pulmonary hypertension, new chest pain, acute chest pain, or cardiogenic shock should raise the suspicion of pulmonary artery dissection, which can result in sudden death. PMID:23670510

  11. 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.

  12. Arterial hypertension in liver transplant recipients.

    PubMed

    Hryniewiecka, E; Zegarska, J; Paczek, L

    2011-10-01

    Hypertension is an important cardiovascular risk factor that influences patient survival. This study sought to evaluate hypertension incidence and circadian rhythms of blood pressure (BP) among liver transplant recipients during the first posttransplant month. We also compared hypertension incidence according to clinical and automated blood pressure monitoring methods. BP was determined by clinical blood pressure monitoring (CBPM) methods and by automated blood pressure monitoring (ABPM) using the SpaceLabs device. We also assessed blood biochemistry, particularly kidney function parameters and immunosuppressive drug blood trough levels, among 32 white subjects (10 women and 22 men) of average age 47.58±14.19 years. The leading cause for transplantation was liver insufficiency due to viral hepatitis B and/or C infection (43.75%). The majority (93.75%) of patients was prescribed immunosuppressive treatment with tacrolimus. Although we observed hypertension in 28 patients (87.5%) by ABPM measurements and in 25 (78.12%) using CBPM method, the difference did not reach statistical significance. However, BP control was inadequate in 28 patients (87.5%) by ABPM assessment versus 3 (9.38%) according to CBPM readings (P=.025). The BP circadian rhythm was altered in 30 patients (93.75%) including 15 with higher nighttime BP readings. There was no correlation between tacrolimus blood levels and BP values or with kidney function as assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. We concluded that prevalence of arterial hypertension among liver transplant recipients within 1 month after transplantation is high. The majority of the patients show disturbed circadian rhythms in the early period after liver transplantation with loss or even reversal of the normal nocturnal decrease in BP. Owing to the fact that ABPM enables more adequate daily assessment of BP values, it is an optimal method to adjust antihypertensive therapy to optimal levels

  13. Arterial hypertension: A neglected risk for bleeding.

    PubMed

    Vogel, Birgit; Mehran, Roxana

    2016-08-01

    The impact of arterial hypertension, one of the most common comorbidities in CAD patients, on bleeding risk after PCI must not be underestimated. More rigorous control of blood pressure during PCI procedure, radial artery access and alternative anticoagulant strategy may be considered in these patients. Further investigation in a more contemporary setting of PCI procedure is warranted. PMID:27530190

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

    PubMed

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

    2013-12-01

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

  15. [Management of arterial hypertension in the elderly].

    PubMed

    Xhignesse, P; Saint-Remy, A; Krzesinski, J M

    2014-01-01

    High blood pressure is very frequent in the elderly; it represents a real threat for the patient's health and a source of huge costs for the economic system. Systolic hypertension is the most frequent form observed in the old, due to large arteries stiffness. Antihypertensive therapy has proven effective to decrease significantly the cardiovascular morbi-mortality and total mortality in this population. A non pharmacological approach is also very useful, but should not be too restrictive. Blood pressure target in patients older than 65 (and, particularly, in octogenarians) is 150/80 mmHg. Blood pressure should be checked in the upright position before changing the drug dosage. The first line therapy in the old should generally be a calcium channel antagonist or a low dose diuretic.

  16. 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.

  17. Medical treatment update on pulmonary arterial hypertension

    PubMed Central

    Burger, Charles

    2015-01-01

    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. PMID:26336595

  18. 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

  19. 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.

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

    PubMed

    Stepien, Rebecca L

    2009-09-01

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

  1. Elastin in large artery stiffness and hypertension.

    PubMed

    Wagenseil, Jessica E; Mecham, Robert P

    2012-06-01

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

  2. PRESSOR SUBSTANCES IN ARTERIAL HYPERTENSION

    PubMed Central

    Schroeder, Henry A.; Perry, H. Mitchell; Dennis, Evie G.; Mahoney, Laura E.

    1955-01-01

    Some pharmacological and chemical qualities of pherentasin, a vasoconstrictor substance procured from human hypertensive blood, were studied by a new assay method using the spirally cut rabbit aorta. Of a number of drugs tested, six metal-binding agents including hydralazine inactivated the active principle. The material was stable in acid but not in alkali. It was destroyed by drying. Chemical analysis and inactivation procedures suggested the presence of primary amine and considerable sulfur; a peptide linkage was suspected because of inactivation by manganous ion and papain. The material was remarkably resistant to most pharmacological agents and appeared to act directly on smooth muscle. PMID:13252186

  3. Immunity in arterial hypertension: associations or causalities?

    PubMed

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

    2015-12-01

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

  4. An Update on Pulmonary Arterial Hypertension

    PubMed Central

    Wapner, Joanna; Matura, Lea Ann

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disease that ultimately leads to right heart failure and death. PAH is defined as a mean pulmonary arterial pressure ≥ 25 mm Hg with a pulmonary capillary wedge pressure ≤ 15 mm Hg at rest. The diagnosis of PAH is one of exclusion; diagnostics include an extensive history, serology, chest radiograph, pulmonary function tests, ventilation/perfusion scan, transthoracic echocardiogram, and right heart catheterization. Treatment and care of patients with PAH can be complex. Therefore, the nurse practitioner is an integral member of the healthcare team caring for PAH patients, helping to ensure seamless care and support. PMID:25954140

  5. Hypertension and renal artery stenosis: a complex clinical scenario.

    PubMed

    Jaff, M R

    2000-10-01

    Hypertension remains the most common reason for patients to visit physicians in the United States. Although awareness of hypertension among patients continues to increase, adequate control of hypertension remains poor. In addition, as the population of patients with hypertension ages, atherosclerosis becomes increasingly prevalent. Atherosclerotic renal artery stenosis is the most common secondary cause of hypertension and can cause hypertension to be difficult to control. Atherosclerotic renal artery stenosis may also result in chronic renal insufficiency. The physician must be aware of the clinical scenarios in which renal artery stenosis may occur, methods of diagnosis, and indications for intervention.

  6. Management of pulmonary arterial hypertension.

    PubMed

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

    2015-05-12

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

  7. Pulmonary arterial hypertension: a clot in question.

    PubMed

    Patel, Bhavin; Pakala, Aneesh; Aronson, Willard; Magharyous, Hany; Brown, Brent

    2014-07-01

    Pulmonary arterial hypertension (PAH) is a group of disorders characterized by a progressive increase in pulmonary vascular resistance leading to right heart failure and premature death. We present an unusual case of PAH diagnosed initially as Idiopathic PAH (IPAH) after secondary causes were excluded which was successfully managed for a number of years with vasodilators and anticoagulation. Over the months after stopping anticoagulation (because of recurring small bowel hemorrhaging) patient developed progressive findings of right heart failure, which failed to respond to escalating doses of prostacyclin. The patient died and an autopsy revealed the surprising finding of extensive organized central pulmonary artery thrombi as is seen in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We discuss the question of whether these thrombi are generally embolic or develop in situ and recommend that clinicians have a high index of suspicion for central thrombi in patients with IPAH were anticoagulation is contraindicated. PMID:25223151

  8. [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

  9. Vitamin D, arterial hypertension & cerebrovascular disease.

    PubMed

    Kienreich, Katharina; Grubler, Martin; Tomaschitz, Andreas; Schmid, Johannes; Verheyen, Nicolas; Rutters, Femke; Dekker, Jacqueline M; Pilz, Stefan

    2013-04-01

    Vitamin D is mainly derived from endogenous ultraviolet-B induced vitamin D synthesis in the skin, and the current high prevalence of vitamin D deficiency can, therefore, largely be attributed to lifestyle related low sunlight exposure. Regulation of bone and mineral metabolism is a classic vitamin D effect, but the identification of the vitamin D receptor (VDR) in almost all human cells suggests a role for vitamin D also in extra-skeletal diseases. Experimental studies demonstrated several antihypertensive and vascular protective effects of vitamin D, such as suppression of the renin angiotensin aldosterone system, beneficial modulation of classic cardiovascular risk factors, and anti-atherosclerotic properties including improvements of endothelial function. Additional neuroprotective actions of vitamin D have also been reported. In line with this, epidemiological studies have largely shown that vitamin D deficiency is an independent risk factor for arterial hypertension and strokes. Data from randomized controlled trials (RCTs) are, however, limited and less promising, with currently no confirmation that vitamin D reduces stroke incidence. Whereas some RCTs suggest that vitamin D supplementation might modestly reduce blood pressure, this has not been consistently observed in all studies. It is, therefore, premature to recommend vitamin D supplementation for the prevention and treatment of arterial hypertension and stroke. Nevertheless, the fact that patients with arterial hypertension and cerebrovascular disease are at a relatively high risk of vitamin D deficiency, and therewith associated musculoskeletal diseases can serve as a rationale for the evaluation, prevention and treatment of vitamin D deficiency in these patients.

  10. Update on pulmonary arterial hypertension pharmacotherapy.

    PubMed

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

    2016-06-01

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

  11. Targeted therapies in pulmonary arterial hypertension.

    PubMed

    Montani, David; Chaumais, Marie-Camille; Guignabert, Christophe; Günther, Sven; Girerd, Barbara; Jaïs, Xavier; Algalarrondo, Vincent; Price, Laura C; Savale, Laurent; Sitbon, Olivier; Simonneau, Gérald; Humbert, Marc

    2014-02-01

    Pulmonary arterial hypertension (PAH) is a rare disorder characterized by progressive obliteration of small pulmonary arteries that leads to elevated pulmonary arterial pressure and right heart failure. During the last decades, an improved understanding of the pathophysiology of the disease has resulted in the development of effective therapies targeting endothelial dysfunction (epoprostenol and derivatives, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors). These drugs allow clinical, functional and hemodynamic improvement. Even though, no cure exists for PAH and prognosis remains poor. Recently, several additional pathways have been suggested to be involved in the pathogenesis of PAH, and may represent innovative therapies. In this summary, we review conventional therapy, pharmacological agents currently available for the treatment of PAH and the benefit/risk ratio of potential future therapies. PMID:24134901

  12. [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.

  13. [Serotonin hypothesis and pulmonary artery hypertension].

    PubMed

    Kloza, Monika; Baranowska-Kuczko, Marta; Pędzińska-Betiuk, Anna; Jackowski, Konrad; Kozłowska, Hanna

    2014-06-06

    Pulmonary arterial hypertension (PAH) is a progressive, complex disease leading to the right ventricular failure and premature death. PAH is characterized by increased pulmonary arterial pressure, increased vascular resistance, pulmonary vascular remodeling and endothelial dysfunction. Pathomechanism of this disease is still unknown. It has been suggested, that endothelial dysfunction is caused by unbalance between vasodilators and vasoconstrictors e.g. serotonin (5-HT). Previously, serotonin hypothesis was linked to the anorexigens, derivatives of fenfluramine, which are serotonin transporter (SERT) substrates. Nowadays, it has been proved that all elements of serotonergic system within pulmonary circulation participate in the developement of PAH. The tryptophan hydroxylase 1 (Tph-1) catalyses synthesis of 5-HT from tryptophan in the pulmonary arterial endothelial cells. 5-HT mediates contraction of pulmonary vessels via 5-HT1B and 5-HT2A receptors. 5-HT is also transported into pulmonary arterial smooth muscle cells via SERT and through activation of reactive oxygen species and Rho-kinase may contribute to contraction or/and, via stimulation of transcription factors, lead to proliferation and remodelling. There is also increasing number of evidence about functional interaction between 5-HT1B receptor and SERT in modulation of vasoconstriction and proliferation in pulmonary arteries. This review discusses the role of 5-HT in the development of PAH and highlights possible therapeutic targets within serotonergic system.

  14. Novel biomarkers for pulmonary arterial hypertension.

    PubMed

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

    2016-01-01

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

  15. [Perinantal programming of arterial hypertension in child].

    PubMed

    Kovtun, O P; Tsyv'ian, P B

    2013-01-01

    There is a growing number of evidence linking fetal intrauterine malnutrition, other adverse events or exposures and arterial hypertension during the following life. After important epidemiological studiesfrom many countries, research now focuses on mechanisms of organ dysfunction and on refining the understanding of the interaction between common elements ofadverse perinatal conditions and normal development. This review focused on advances in comprehension of the influence of intrauterine malnutrition on developmental programming of hypertension. Significant decrease in nephrons number was demonstrated as a result of fetal asymmetrical growth restriction syndrome both in human and experimental animal model. The role of malnutrition and dexametasone induced rennin-angiotensin system inhibition in fetal and newborn nephrogenesis is discussed. Recent studies have revealed important mechanisms of altered vascular function and structure as well as sympathetic regulation of the cardiovascular system in perinatal hypertension models. Some of adverse effects on nephrogenesis and blood pressure regulation could be reversed by special diet and treatment during first two years of life. While the complexity of the interactions between antenatal and postnatal influences on blood pressure is increasingly recognized, the importance of early postnatal life in modulating developmental programming offers the hope of a critical 1000 days window of opportunity to reverse programming and prevent or reduce child hypertension.

  16. [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. PMID:21536178

  17. 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. PMID:26341985

  18. Severe gastric variceal haemorrhage due to splenic artery thrombosis and consecutive arterial bypass

    PubMed Central

    2011-01-01

    Background Upper gastrointestinal haemorrhage is mainly caused by ulcers. Gastric varicosis due to portal hypertension can also be held responsible for upper gastrointestinal bleeding. Portal hypertension causes the development of a collateral circulation from the portal to the caval venous system resulting in development of oesophageal and gastric fundus varices. Those may also be held responsible for upper gastrointestinal haemorrhage. Case presentation In this study, we describe the case of a 69-year-old male with recurrent severe upper gastrointestinal bleeding caused by arterial submucosal collaterals due to idiopathic splenic artery thrombosis. The diagnosis was secured using endoscopic duplex ultrasound and angiography. The patient was successfully treated with a laparoscopic splenectomy and complete dissection of the short gastric arteries, resulting in the collapse of the submucosal arteries in the gastric wall. Follow-up gastroscopy was performed on the 12th postoperative week and showed no signs of bleeding and a significant reduction in the arterial blood flow within the gastric wall. Subsequent follow-up after 6 months also showed no further gastrointestinal bleeding as well as subjective good quality of life for the patient. Conclusion Submucosal arterial collaterals must be excluded by endosonography via endoscopy in case of recurrent upper gastrointestinal bleeding. Laparoscopic splenectomy provides adequate treatment in preventing any recurrent bleeding, if gastric arterial collaterals are caused by splenic artery thrombosis. PMID:21711534

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

    PubMed

    Kawut, Steven M

    2014-06-01

    Epidemiologic patterns of pulmonary arterial hypertension differ by era and region and may shed light on the pathophysiology and treatment of the disease. New efforts to target one or more of the recently studied therapies could establish personalized medicine as standard care in pulmonary arterial hypertension. PMID:25164214

  20. [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.

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  3. 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.

  4. 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

  5. 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. PMID:27590754

  6. 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.

  7. 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

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

    PubMed

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

    2015-06-01

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

  9. 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.

  10. Reversible pre-capillary pulmonary hypertension due to dasatinib.

    PubMed

    Buchelli Ramirez, Herminia L; Álvarez Álvarez, Celso M; Rodríguez Reguero, José J; García Clemente, Marta M; Casan Clarà, Pere

    2014-05-01

    Pulmonary arterial hypertension and secondary pleural effusion have been reported in association with long-term therapy with the multi-tyrosine kinase inhibitor dasatinib, approved for the treatment of chronic myeloid leukemia. Here, we present the case of a 50-year-old man, diagnosed with chronic myeloid leukemia in August 2003, who developed pulmonary arterial hypertension after > 4 years of treatment with dasatinib. The complete remission of pulmonary arterial hypertension following dasatinib discontinuation suggests an etiological role of the drug in its development, although the administration of sildenafil may have played a therapeutic role. PMID:24149673

  11. Pulmonary arterial hypertension: a review in pharmacotherapy.

    PubMed

    Patel, Bhaumik B; Feng, Ying; Cheng-Lai, Angela

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disease that remains incurable. The past 2 decades have witnessed many advances in PAH-directed therapies. More recently, 3 new oral agents have become available in the United States within the past 2 years. Treprostinil is now available in extended-release oral tablets. Macitentan is the third endothelin receptor antagonist approved for use, demonstrating benefits on morbidity and mortality among patients with PAH in an event-driven study. Riociguat is the first soluble guanylate cyclase stimulator that has been approved for use in the United States. This article reviews the clinical efficacy and safety of these 3 agents and the roles they play in the management of PAH. Additionally, we review the limitations of using surrogate markers such as change in 6-minute walk distance to assess disease progression.

  12. [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. PMID:23859515

  13. Right Ventricular Dysfunction in Systemic Sclerosis Associated Pulmonary Arterial Hypertension

    PubMed Central

    Tedford, Ryan J.; Mudd, James O.; Girgis, Reda E.; Mathai, Stephen C.; Zaiman, Ari L.; Housten-Harris, Traci; Boyce, Danielle; Kelemen, Benjamin W.; Bacher, Anita C.; Shah, Ami A.; Hummers, Laura K.; Wigley, Fredrick M.; Russell, Stuart D.; Saggar, Rajeev; Saggar, Rajan; Maughan, W. Lowell; Hassoun, Paul M.; Kass, David A.

    2013-01-01

    Background Systemic sclerosis associated pulmonary artery hypertension (SScPAH) has a worse prognosis compared to idiopathic pulmonary arterial hypertension (IPAH), with a median survival of 3 years after diagnosis often due to right ventricular (RV) failure. We tested if SScPAH or systemic sclerosis related pulmonary hypertension with interstitial lung disease (SSc-ILD-PH) imposes a greater pulmonary vascular load than IPAH and/or leads to worse RV contractile function. Methods and Results We analyzed pulmonary artery pressures and mean flow in 282 patients with pulmonary hypertension (166 SScPAH, 49 SSc-ILD-PH, 67 IPAH). An inverse relation between pulmonary resistance (RPA) and compliance (CPA) was similar for all three groups, with a near constant resistance × compliance product. RV pressure-volume loops were measured in a subset, IPAH (n=5) and SScPAH (n=7) as well as SSc without PH (SSc-no-PH, n=7) to derive contractile indexes (end-systolic elastance [Ees] and preload recruitable stroke work [Msw]), measures of right ventricular load (arterial elastance [Ea]), and RV-pulmonary artery coupling (Ees/Ea). RV afterload was similar in SScPAH and IPAH (RPA=7.0±4.5 vs. 7.9±4.3 Wood units; Ea=0.9±0.4 vs. 1.2±0.5 mmHg/mL; CPA=2.4±1.5 vs. 1.7±1.1 mL/mmHg; p>0.3 for each). Though SScPAH did not have greater vascular stiffening compared to IPAH, RV contractility was more depressed (Ees=0.8±0.3 vs. 2.3±1.1, p<0.01; Msw=21±11 vs. 45±16, p=0.01), with differential RV-PA uncoupling (Ees/Ea=1.0±0.5 vs. 2.1±1.0, p=.03). This ratio was higher in SSc-no-PH (Ees/Ea = 2.3±1.2, p=0.02 vs. SScPAH). Conclusions RV dysfunction is worse in SScPAH compared to IPAH at similar afterload, and may be due to intrinsic systolic function rather than enhanced pulmonary vascular resistive and/or pulsatile loading. PMID:23797369

  14. Macitentan for the treatment of pulmonary arterial hypertension.

    PubMed

    Spikes, L; Williamson, T; Satterwhite, L

    2014-06-01

    Macitentan is a novel, dual endothelin receptor antagonist recently approved for the treatment of WHO Group I pulmonary arterial hypertension. Its pharmacologic mechanism of action as well as the pharmacokinetics, pharmacodynamics and potential drug-drug interactions have been demonstrated in multiple phase I and II trials. The pivotal randomized, placebo-controlled, event-driven clinical trial revealed a significant reduction in morbidity. The most common adverse events were rarely clinically significant, nor did they result in a high rate of discontinuation. Of note, macitentan is contraindicated in pregnant women due to embryo-fetal toxicity.

  15. 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.

  16. A Contemporary Approach to Pulmonary Arterial Hypertension.

    PubMed

    Krishnan, Udhay; Horn, Evelyn M

    2016-09-01

    In recent years, there have been major changes in the landscape of pulmonary arterial hypertension therapy with the introduction of novel agents and innovative treatment strategies for this progressive disease. The aim of this review is to discuss the evolution in trial design in this field and highlight the salient features of recently published studies. We also summarize our approach to therapy selection in this chronic disease and identify areas for future exploration. The therapeutic armamentarium now includes 13 approved therapies. While most of these agents have been studied in small, short-term trials using the 6-min walk distance as a primary endpoint, there has been a shift in recent years toward larger, long-term, event-driven trials that utilize combined morbidity and mortality endpoints. The SERAPHIN and GRIPHON trials were two such studies, which led to the approval of the dual endothelin-receptor antagonist macitentan and the selective prostacyclin receptor antagonist selexipag, respectively. Other event-driven trials, like AMBITION and COMPASS-2, have provided valuable insight into the use of combined oral therapies in symptomatic patients. In conclusion, despite being a more manageable disease in the modern treatment era, pulmonary hypertension is still associated with considerable morbidity and much more work remains to be done in this field. Important questions remain about the most optimal way to manage patients and conduct trials going forward. PMID:27491673

  17. Genetics Home Reference: pulmonary arterial hypertension

    MedlinePlus

    ... Primary pulmonary hypertension 2 Primary pulmonary hypertension 3 Primary pulmonary hypertension 4 ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific articles on PubMed (1 link) PubMed OMIM (4 links) ...

  18. 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. PMID:24582963

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

    PubMed

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

    2013-08-01

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

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

    PubMed

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

    2016-06-01

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

  1. [New guidelines 2007 for the management of arterial hypertension].

    PubMed

    Krzesinski, J M; Xhignesse, P

    2007-09-01

    New guidelines for the management of arterial hypertension have just been released by the European Societies of Cardiology and Arterial Hypertension. The global cardiovascular risk is again at the center of this management. The control of high blood pressure goes through an adequate use of antihypertensive agents and the application of healthy lifestyle and diet recommendations. Again, management of all the cardiovascular risk factors is stimulated.

  2. Epistatic interactions in idiopathic pulmonary arterial hypertension

    PubMed Central

    Vadapalli, Shivani; Satyanarayana, M. L.; Chaitra, K. L.; Rani, H. Surekh; Sastry, B.K.S.; Nallari, Pratibha

    2012-01-01

    BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is a poorly understood complex disorder, which results in progressive remodeling of the pulmonary artery that ultimately leads to right ventricular failure. A two-hit hypothesis has been implicated in pathogenesis of IPAH, according to which the vascular abnormalities characteristic of PAH are triggered by the accumulation of genetic and/or environmental insults in an already existing genetic background. The multifactor dimensionality reduction (MDR) analysis is a statistical method used to identify gene–gene interaction or epistasis and gene–environment interactions that are associated with a particular disease. The MDR method collapses high-dimensional genetic data into a single dimension, thus permitting interactions to be detected in relatively small sample sizes. AIM: To identify and characterize polymorphisms/genes that increases the susceptibility to IPAH using MDR analysis. MATERIALS AND METHODS: A total of 77 IPAH patients and 100 controls were genotyped for eight polymorphisms of five genes (5HTT, EDN1, NOS3, ALK-1, and PPAR-γ2). MDR method was adopted to determine gene–gene interactions that increase the risk of IPAH. RESULTS: With MDR method, the single-locus model of 5HTT (L/S) polymorphism and the combination of 5HTT(L/S), EDN1(K198N), and NOS3(G894T) polymorphisms in the three-locus model were attributed to be the best models for predicting susceptibility to IPAH, with a P value of 0.05. CONCLUSION: MDR method can be useful in understanding the role of epistatic and gene–environmental interactions in pathogenesis of IPAH. PMID:22754222

  3. Breath Analysis in Pulmonary Arterial Hypertension

    PubMed Central

    Cikach, Frank S.; Tonelli, Adriano R.; Barnes, Jarrod; Paschke, Kelly; Newman, Jennie; Grove, David; Dababneh, Luma; Wang, Sihe

    2014-01-01

    Background: Pulmonary arterial hypertension (PAH) is a progressive and devastating condition characterized by vascular cell proliferation and is associated with several metabolic derangements. We hypothesized that metabolic derangements in PAH can be detected by measuring metabolic by-products in exhaled breath. Methods: We collected breath and blood samples from patients with PAH at the time of right-sided heart catheterization (n = 31) and from healthy control subjects (n = 34). Breath was analyzed by selected ion flow tube-mass spectrometry in predetermined training and validation cohorts. Results: Patients with PAH were 51.5 ± 14 years old, and 27 were women (85%). Control subjects were 38 ± 13 years old, and 22 were women (65%). Discriminant analysis in the training set identified three ion peaks (H3O+29+, NO+56+, and O2+98+) and the variable age that correctly classified 88.9% of the individuals. In an independent validation cohort, 82.8% of the individuals were classified correctly. The concentrations of the volatile organic compounds 2-propanol, acetaldehyde, ammonia, ethanol, pentane, 1-decene, 1-octene, and 2-nonene were different in patients with PAH compared with control subjects. Exhaled ammonia was higher in patients with PAH (median [interquartile range]: 94.7 parts per billion (ppb) [70-129 ppb] vs 60.9 ppb [46-77 ppb], P < .001) and was associated with right atrial pressure (ρ = 0.57, P < .001), mean pulmonary artery pressure (ρ = 0.43, P = .015), cardiac index by thermodilution (ρ = −0.39, P = .03), pulmonary vascular resistance (ρ = 0.40, P = .04), mixed venous oxygen (ρ = −0.59, P < .001), and right ventricular dilation (ρ = 0.42, P = .03). Conclusions: Breathprint is different between patients with PAH and healthy control subjects. Several specific compounds, including ammonia, were elevated in the breath of patients with PAH. Exhaled ammonia levels correlated with severity of disease. PMID:24091389

  4. Controversies in pulmonary hypertension due to left heart disease

    PubMed Central

    Cheli, Martino

    2015-01-01

    Left heart failure is currently the most prevalent cause of pulmonary hypertension (PH) worldwide and this is due mainly to the increased left ventricular and pulmonary venous pressures seen in this condition. Still, a quota of patients with left heart failure will have a pulmonary arterial disease “disproportionate” to the initial increase of left-sided pressures. Whatever the mechanism involved, the appearance of PH is a powerful marker, as it determines decreased exercise tolerance and survival. To date, all trials using therapies approved for pulmonary arterial hypertension (PAH) failed to demonstrate a benefit in the context of heart failure (HF) without or with PH. In addition, the comparison among studies is limited by relevant differences in definitions, methodology, and timing of assessment. A novel rigorous hemodynamic classification based on the diastolic pulmonary gradient has been recently proposed to better characterize this form of PH. This will promote uniformity in patient populations and end-points for future clinical trials. PMID:25705390

  5. [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. PMID:27284843

  6. [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.

  7. CD133+ cells in pulmonary arterial hypertension.

    PubMed

    Foris, Vasile; Kovacs, Gabor; Marsh, Leigh M; Bálint, Zoltán; Tötsch, Martin; Avian, Alexander; Douschan, Philipp; Ghanim, Bahil; Klepetko, Walter; Olschewski, Andrea; Olschewski, Horst

    2016-08-01

    Circulating mononuclear cells may play an important role for the vascular remodelling in pulmonary arterial hypertension (PAH), but studies addressing multiple progenitor populations are rare and inconsistent.We used a comprehensive fluorescence-activated cell sorting analysis of circulating mononuclear cells in 20 PAH patients and 20 age- and sex-matched controls, and additionally analysed CD133(+) cells in the lung tissue of five PAH transplant recipients and five healthy controls (donor lungs).PAH patients were characterised by increased numbers of circulating CD133(+) cells and lymphopenia as compared with control. In PAH, CD133(+) subpopulations positive for CD117 or CD45 were significantly increased, whereas CD133(+)CD309(+), CD133(+)CXCR2(+) and CD133(+)CD31(+) cells were decreased. In CD133(+) cells, SOX2, Nanog, Ki67 and CXCR4 were not detected, but Oct3/4 mRNA was present in both PAH and controls. In the lung tissue, CD133(+) cells included three main populations: type 2 pneumocytes, monocytes and undifferentiated cells without significant differences between PAH and controls.In conclusion, circulating CD133(+) progenitor cells are elevated in PAH and consist of phenotypically different subpopulations that may be up- or downregulated. This may explain the inconsistent results in the literature. CD133(+) type 2 pneumocytes in the lung tissue are not associated with circulating CD133(+) mononuclear cells. PMID:27103380

  8. Updated treatment algorithm of pulmonary arterial hypertension.

    PubMed

    Galiè, Nazzareno; Corris, Paul A; Frost, Adaani; Girgis, Reda E; Granton, John; Jing, Zhi Cheng; Klepetko, Walter; McGoon, Michael D; McLaughlin, Vallerie V; Preston, Ioana R; Rubin, Lewis J; Sandoval, Julio; Seeger, Werner; Keogh, Anne

    2013-12-24

    The demands on a pulmonary arterial hypertension (PAH) treatment algorithm are multiple and in some ways conflicting. The treatment algorithm usually includes different types of recommendations with varying degrees of scientific evidence. In addition, the algorithm is required to be comprehensive but not too complex, informative yet simple and straightforward. The type of information in the treatment algorithm are heterogeneous including clinical, hemodynamic, medical, interventional, pharmacological and regulatory recommendations. Stakeholders (or users) including physicians from various specialties and with variable expertise in PAH, nurses, patients and patients' associations, healthcare providers, regulatory agencies and industry are often interested in the PAH treatment algorithm for different reasons. These are the considerable challenges faced when proposing appropriate updates to the current evidence-based treatment algorithm.The current treatment algorithm may be divided into 3 main areas: 1) general measures, supportive therapy, referral strategy, acute vasoreactivity testing and chronic treatment with calcium channel blockers; 2) initial therapy with approved PAH drugs; and 3) clinical response to the initial therapy, combination therapy, balloon atrial septostomy, and lung transplantation. All three sections will be revisited highlighting information newly available in the past 5 years and proposing updates where appropriate. The European Society of Cardiology grades of recommendation and levels of evidence will be adopted to rank the proposed treatments. PMID:24355643

  9. Mitochondrial Haplogroups and Risk of Pulmonary Arterial Hypertension.

    PubMed

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

    2016-01-01

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

  10. Mitochondrial Haplogroups and Risk of Pulmonary Arterial Hypertension

    PubMed Central

    Farha, Samar; Hu, Bo; Comhair, Suzy; Zein, Joe; Dweik, Raed

    2016-01-01

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

  11. Effects of portal hypertension on responsiveness of rat mesenteric artery and aorta.

    PubMed Central

    Cawley, T; Geraghty, J; Osborne, H; Docherty, J R

    1995-01-01

    1. We have examined the effects of pre-hepatic portal hypertension on the responsiveness of rat small mesenteric arteries and aorta. Rats were made portal hypertensive by creating a calibrated portal vein stenosis, or sham-operated. 2. In rat mesenteric arteries, there was no significant difference between portal hypertensive and sham-operated animals in the contractile potency of noradrenaline (NA), but the maximum contractile responses to NA, U46619 and KCl were significantly increased in vessels from portal hypertensive animals. This altered maximum contractile response was not due to alterations in smooth muscle mass. 3. In rat mesenteric arteries, there were no significant differences between portal hypertensive and sham-operated animals in endothelium-dependent relaxations to acetylcholine (ACh). The difference between portal hypertensive and sham-operated rats in the maximum response to U46619 was maintained following a combination of methylene blue (1 microM) and NG-monomethyl-L-arginine (100 microM), suggesting that any differences in endothelial function do not explain differences in the response to vasoconstrictors. 4. In rat aorta, there were no significant differences between portal hypertensive and sham-operated animals in the contractile response to NA or KCl or in the endothelium-dependent relaxations to ACh. 5. In pithed rats, there was no difference between portal hypertensive and sham-operated animals in the pressor potency of NA. 6. It is concluded that portal hypertension produces an increase in the contractile response to the vasoconstrictors NA, U46619 and KCl in rat mesenteric arteries but not in the aorta. This suggests that the diminished responsiveness to vasoconstrictors reported in portal hypertensive rats in vivo is not due to a diminished responsiveness at the level of the vascular smooth muscle. PMID:7773539

  12. [Arterial hypertension in special situations: mild, systolic and in pregnancy].

    PubMed

    Luque Otero, M; Fernández Pinilla, C

    1990-01-01

    Mild hypertension is very common, 50% of hypertensives being with their diastolic BP between 90 and 104 mmHg. Many large studies, especially HDFP, had shown not only the deleterious cardiovascular effects of mild hypertension but also the benefits obtained with the therapy. The non-pharmacological approach should be the first step in the treatment of mild hypertension. Isolated systolic hypertension have a high prevalence in the elderly, increasing the cardiovascular morbidity and mortality. Sodium restriction and, if necessary, vasodilators increasing the arterial compliance seem to be the logical approach to treat isolated systolic hypertension. Finally, eclampsia is the most serious complication of pregnancy - induced hypertension. The treatment with bed rest and either betablockers or methyldopa is beneficial. If eclampsia occurs hydralazine, magnesium sulphate or nifedipine should be used.

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

    PubMed

    Di Daniele, Nicola

    2015-12-01

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

  14. Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension.

    PubMed

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

    2014-06-20

    This review summarizes an expanding body of knowledge indicating that failure to resolve inflammation and altered immune processes underlie the development of pulmonary arterial hypertension. The chemokines and cytokines implicated in pulmonary arterial hypertension that could form a biomarker platform are discussed. Pre-clinical studies that provide the basis for dysregulated immunity in animal models of the disease are reviewed. In addition, we present therapies that target inflammatory/immune mechanisms that are currently enrolling patients, and discuss others in development. We show how genetic and metabolic abnormalities are inextricably linked to dysregulated immunity and adverse remodeling in the pulmonary arteries. PMID:24951765

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

    PubMed

    Pietri, Panagiota; Vlachopoulos, Charalambos; Tousoulis, Dimitris

    2015-01-01

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

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

    PubMed

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

    2002-07-01

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

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

    PubMed

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

    2015-01-01

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

  18. Two rare conditions in an Eisenmenger patient: left main coronary artery compression and Ortner's syndrome due to pulmonary artery dilatation.

    PubMed

    Andjelkovic, Kristina; Kalimanovska-Ostric, Dimitra; Djukic, Milan; Vukcevic, Vladan; Menkovic, Nemanja; Mehmedbegovic, Zlatko; Topalovic, Mirko; Tesic, Milorad

    2013-01-01

    The left-main coronary artery extrinsic compression due to enlarged pulmonary artery has been described in several case series. Ortner's syndrome is also a rare condition in some cardiovascular disorders. There have been no reports about these two rare conditions in the same patient. Hence, we report a very rare case of an Eisenmenger patient with severe pulmonary hypertension and dilated pulmonary artery which has compressed the left main coronary artery, severely narrowing it, and the left laryngeal recurrent nerve with subsequent Ortner's syndrome and brief literature review. PMID:23831302

  19. 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

  20. 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. PMID:26084306

  1. 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.

  2. [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. PMID:10517096

  3. In vivo hypertensive arterial wall uptake of radiolabeled liposomes

    SciTech Connect

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

    1990-06-01

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

  4. [Primary and secondary arterial hypertension - update 2016].

    PubMed

    Sanner, Bernd; Hausberg, Martin

    2016-06-01

    In patients with hypertension without diabetes and with an increased risk of cardiovascular complications a blood pressure of below 130 mmHg should be targeted. Hypertensive patients with an age above 80 years should be treated in the same way as younger hypertensive patients if they are otherwise healthy and functionally independent. On the other hand frail elderly patients could have an increased morbidity and mortality with intensive blood pressure control. In patients with resistant hypertension spironolactone was the most effective drug when given in addition to their baseline drugs (ACE-inhibitor/angiotensin receptor antagonist, calcium channel blocker and thiazide diuretic). PMID:27254628

  5. Novel Strategies in the Treatment of Pulmonary Arterial Hypertension.

    PubMed

    Madonna, Rosalinda; Cocco, Nino

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a pathophysiological condition characterized by increased pulmonary vascular resistance (PVR), initially due to abnormal pulmonary vasoconstriction in response to endothelial injury. Recent studies confirmed the key role of endothelin (ET)-1 in the vasoconstriction and remodeling of pulmonary microcirculation during PAH. In responders patients, classical treatments for PAH are prostanoids, phosphodiesterase (PDE)-5 inhibitors and endothelin receptor antagonists (ERAs), which target prostaglandin I2, nitric oxide and endothelin pathways, respectively. Randomised, placebo-controlled trials have shown that ERAs improves haemodynamic parameters of the pulmonary circulation, functional capacity and clinical outcome in patients affected by PAH. Here, we will review the definition, classification and pathophysiology of PH. Furthermore, we will provide an up-to-date overview of currently recommended diagnostic and therapeutic work-up in PAH. PMID:26201488

  6. [Vascular damage in arterial hypertension: its noninvasive assessment].

    PubMed

    Novo, S; Failla, G; Liquori, M; Longo, B; Gennaro, C; Corda, M; Barbagallo, M; Abrignani, M G; Barbagallo Sangiorgi, G; Strano, A

    1991-12-01

    Arterial hypertension is a definite risk factor for the atherosclerotic disease and thus has a primary role in the genesis of cardiovascular diseases, but it acts also though a direct structural damage of great and small arteries and arterioles. Up to date, clinical research and technological advancements have made possible the development of instruments and methods for the evaluation of the vascular damage. Ultrasonographic methods are now the better non invasive tools for the study of arterial diseases, allowing a definition power comparable to angiography, and giving useful data on characters and composition of plaques, also minimal, at the level of the arterial district of lower limbs, epiaortic, renal, and abdominal vessels. These methods allow the study of the vascular lesion under the hemodynamic (CW or pulsed Doppler with spectral signal analysis) and the morphological profile (high resolution echotomography) or both echo-Doppler duplex scanning or color flow imaging). Arterial compliance of great vessels can be studied through the Doppler evaluation of pulsed wave velocity along the arterial tree. Other useful parameters are the aortic distensibility (ratio between % change in arterial volume and blood pressure), the elastic module, the index of arterial rigidity and the aortic index (ratio between pulse pressure and stroke volume). By using this latter parameter we demonstrated a significant decrease of arterial compliance that is proportional to the severity of blood pressure values. Small vessels may be studied through strain-gauge plethysmography, that allows to obtain the regional blood flows at the hand and forearm (skin circulation) and the calf (muscular circulation) both in basal conditions and after ischaemic stimulus. From the ratio between mean arterial pressure and post-ischemic blood flow it is possible to obtain minimal vascular resistances, expression of the maximal vasodilatation capacity in the arteriolar bed. With this method we showed

  7. [Arterial hypertension among oil-drilling workers exposed to noise].

    PubMed

    Souto Souza, N S; Carvalho, F M; de Cássia Pereira Fernandes, R

    2001-01-01

    A cross-sectional study with a retrospective component was conducted to evaluate occupational noise exposure as a potential risk factor for arterial hypertension among 775 workers from an oil-drilling industry. Hypertension was defined as >/= 140/90mmHg. Occupational noise exposure was measured as: (1) exposure to sound pressure levels >/= 85dbA for 10 years or more and (2) moderate-to-severe noise-induced hearing loss (NIHL). The effects of age, education, shift work, and obesity were evaluated by stratification and logistic regression analysis. A positive association between occupational noise exposure and hypertension was found, using both the level/duration of noise exposure (RP = 1.8; 95% CI: 1.3-2.4) and NIHL (RP = 1.5; 95% CI: 1.1-2.0) as exposure indicators. Considering the study limits, long-term occupational noise exposure thus appears to be a risk factor for arterial hypertension. PMID:11784909

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

    PubMed

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

    2016-01-01

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

  9. [Arterial hypertension in gravidity - a risk factor for cardiovascular diseases].

    PubMed

    Kováčová, M; Kiňová, S

    2012-12-01

    Gravidity is a dynamic process and complications may occur at any stage and anytime during a thus far physiological gravidity. Such gravidity puts the mother, the foetus and, later, the newborn at a greater risk. The incidence of arterial hypertension is between 7 and 15% and is one of the 4 main causes of maternal and perinatal mortality. Cardiovascular stress test, such as gravidity, might help to identify women at a greater risk of cardiovascular diseases or with a subclinical vascular disease. Women with a history of preeclampsia are more likely to develop chronic arterial hypertension in the future either alone or associated with a cardiovascular disease. Arterial hypertension during gravidity should be considered as a risk factor for cardiovascular diseases during later stages of maternal life. Prevention of cardiovascular diseases should be a life-long aspiration.

  10. Hypercorticism--a risk factor in arterial hypertension and atherosclerosis.

    PubMed

    Berceanu-Gabrielescu, A; Mănciulescu, D; Marinescu, I; Popovici, D; Dinulescu, E; Juvină, E; Ioaniţiu, D; Tache, A; Cristoveanu, A; Ciocirdia, C; Bunea, M; Sooliuc, E; Panaitiu, G; Augustin, M

    1981-01-01

    The present work has attempted an analysis of the role hypercorticism as a risk factor in arterial hypertension and atherosclerosis. Our series consisted of 149 male and female patients of various ages. The incidence of cardiovascular disorders in relation to age and the glucidic lipidic metabolic disorders were also investigated. The results showed that hypercorticism may trigger in very young patients as well arterial hypertension (AH) and glucidic-lipid metabolic disorders both incriminated as risk factors in including atherosclerosis. Hypercorticism was proved to be an aggravating factor of pre-existing cardiopathy. Efficient management of adrenocortical hormones excess brings complete resolution of arterial hypertension and glucidic lipid metabolic disorders in young patients and most adult patients who had no cardiovascular complaints prior to the endocrine syndrome.

  11. 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.

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

    PubMed

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

    2015-01-01

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

  13. Notch3 signaling promotes the development of pulmonary arterial hypertension.

    PubMed

    Li, Xiaodong; Zhang, Xiaoxue; Leathers, Robin; Makino, Ayako; Huang, Chengqun; Parsa, Pouria; Macias, Jesus; Yuan, Jason X-J; Jamieson, Stuart W; Thistlethwaite, Patricia A

    2009-11-01

    Notch receptor signaling is implicated in controlling smooth muscle cell proliferation and in maintaining smooth muscle cells in an undifferentiated state. Pulmonary arterial hypertension is characterized by excessive vascular resistance, smooth muscle cell proliferation in small pulmonary arteries, leading to elevation of pulmonary vascular resistance, right ventricular failure and death. Here we show that human pulmonary hypertension is characterized by overexpression of NOTCH3 in small pulmonary artery smooth muscle cells and that the severity of disease in humans and rodents correlates with the amount of NOTCH3 protein in the lung. We further show that mice with homozygous deletion of Notch3 do not develop pulmonary hypertension in response to hypoxic stimulation and that pulmonary hypertension can be successfully treated in mice by administration of N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a gamma-secretase inhibitor that blocks activation of Notch3 in smooth muscle cells. We show a mechanistic link from NOTCH3 receptor signaling through the Hairy and enhancer of Split-5 (HES-5) protein to smooth muscle cell proliferation and a shift to an undifferentiated smooth muscle cell phenotype. These results suggest that the NOTCH3-HES-5 signaling pathway is crucial for the development of pulmonary arterial hypertension and provide a target pathway for therapeutic intervention. PMID:19855400

  14. Macitentan in pulmonary arterial hypertension: The SERAPHIN trial.

    PubMed

    Said, Karim

    2014-01-01

    Major limitations of pulmonary arterial hypertension (PAH) drug trials include the small number of enrolled patients, short term follow up (12-16 weeks), and lack of morbidity and mortality primary endpoints. The recently published SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial Hypertension to Improve cliNical outcome) trial represents an important landmark in the history of clinical trials in PAH being the largest and longest clinical study conducted thus far in PAH patients with morbidity and mortality events as primary endpoint. SERAPHIN trial investigated whether long-term treatment with the new endothelin receptor antagonist macitentan would reduce the risk of mortality and morbidity in PAH patients.

  15. 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

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

    PubMed

    Sarigianni, Maria; Dimitrakopoulos, Konstantinos; Tsapas, Apostolos

    2014-05-01

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

  17. Severe Pulmonary Arterial Hypertension: Comprehensive Evaluation by Magnetic Resonance Imaging

    PubMed Central

    Ibrahim, El-Sayed H.; Bajwa, Abubakr A.

    2015-01-01

    Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary artery (PA) pressure, which negatively affects the right ventricular (RV) function. This report shows a patient with severe PAH, on whom a comprehensive MRI exam was performed to evaluate both PA and RV. New imaging sequences were implemented for obtaining additional parameters about the patient's condition. The results show the capabilities of the developed exam of providing complete picture of the cardiovascular system in PAH, which helps the physician optimize treatment. PMID:26435871

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

    PubMed

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

    2016-10-01

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

  19. [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. PMID:27303586

  20. 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

  1. [Health beliefs for the control of arterial hypertension].

    PubMed

    Pires, Cláudia Geovana da Silva; Mussi, Fernanda Carneiro

    2008-12-01

    Health beliefs can interfere with the adherence to arterial hypertension therapy. The aim of this descriptive-exploratory study that adopted the Model of Health Beliefs as a theoretical reference was to estimate percentages of health beliefs about the benefits of prevention and control measures of arterial hypertension and to identify the social-demographic factors associated with these beliefs. The study was conducted in a Health Center in the city of Salvador, with 106 adults self-declared as black, and with a medical diagnosis of arterial hypertension. For the interviews we used a "Scale of Health Beliefs" about 13 behaviors related to disease prevention and control measures. The data analysis was based on percentage rates, frequency of cases and scores and the social-demographic factors associated to these beliefs were analyzed based on the prevalence rate. The global analysis showed predominance in the category "beliefs about benefits" for 12 behaviors. Men and women realized different benefits from these behaviors. The socio-economically less favored strata, young adults and individuals living without a partner tended to perceive less benefits from the prevention and control measures of arterial hypertension.

  2. [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. PMID:25577549

  3. [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.

  4. [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.

  5. Resistant Hypertension due to Fibromuscular Dysplasia in a Young Male: A Rare Case Report.

    PubMed

    Vakili, Hossein; Khaheshi, Isa; Memaryan, Mehdi; Sadeghi, Roxana; Naderian, Mohammadreza

    2016-06-01

    Fibromuscular Dysplasia (FMD) is a sporadic non-atherosclerotic disease. FMD has been established in nearly every arterial bed. However, the most frequent arteries affected are the renal and carotid arteries. Disease presentation may vary broadly, depending upon the arterial bed complication and the severity of illness. Hypertension, particularly resistant type, headache and dizziness are the most common presentations. String of beads appearance in angiographic views due to post-stenotic aneurysms is the characteristic view. It is most commonly described in young aged females; but in rare male cases has also been reported. Moreover, balloon angioplasty is standard and effective therapy for FMD. We present a young 28-year-old man who was referred for evaluation of resistant hypertension for nearly 3 years without comprehensive workup. The patient underwent renal artery angiography which confirmed beading narrowing of the right renal artery with significant stenosis at mid portion compatible with FMD; and balloon angioplasty was done. This case highlights that FMD should be kept in mind as a rare cause of resistant hypertension in young males; although it is most common in young females. PMID:27504335

  6. Extracellular matrix protein gene expression in atherosclerotic hypertensive pulmonary arteries.

    PubMed Central

    Botney, M. D.; Kaiser, L. R.; Cooper, J. D.; Mecham, R. P.; Parghi, D.; Roby, J.; Parks, W. C.

    1992-01-01

    Lobar pulmonary arteries from patients with unexplained pulmonary hypertension were obtained at the time of single-lung transplantation to determine the response of large elastic vessels to increased intraluminal pressure. Specifically, human pulmonary arteries were examined to determine if remodeling remained active at the time of surgery and whether remodeling was similar to previously reported remodeling observed in several animal models. Grossly, the hypertensive vessels appeared atherosclerotic. Histochemical stains revealed a thick, diffuse neointima in hypertensive vessels compared with normal vessels. Immunohistochemistry demonstrated elastin protein in the neointima and in situ hybridization studies demonstrated tropoelastin mRNA largely in the neointima. Similarly, immunohistochemistry and in situ hybridization detected cellular fibronectin, thrombospondin and type I collagen protein and mRNA within the thickened intima from hypertensive vessels. These studies provide evidence that hypertensive vessels in patients with severe chronic pulmonary hypertension are actively remodeling but that the pattern of remodeling is different from previously described animal models. Images Figure 1 Figure 2 Figure 3 PMID:1739129

  7. Prevalence of coronary artery-pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension.

    PubMed

    Lee, Noel S; Blanchard, Daniel G; Knowlton, Kirk U; McDivit, Anna M; Pretorius, Victor; Madani, Michael M; Fedullo, Peter F; Kerr, Kim M; Kim, Nick H; Poch, David S; Auger, William R; Daniels, Lori B

    2015-06-01

    This study sought to determine the prevalence of coronary artery-pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to correlate their presence with the degree of clot burden. CTEPH is a treatable cause of severe pulmonary hypertension and right heart failure. Bronchopulmonary collateral vessels have been used as a supplementary diagnostic and prognostic tool for this disease. Coronary artery-pulmonary artery collaterals in this population have not been described. The coronary angiograms of 300 consecutive patients with CTEPH evaluated for pulmonary thromboendarterectomy (PTE) between January 1, 2007, and May 1, 2014, were examined. Of these patients, 259 (50% male; mean age, 58.3 ± 10.6 years) had cineangiographic images deemed adequate to definitively assess for the presence of coronary artery-pulmonary artery collaterals and were included in the final analyses. Pulmonary angiogram reports were reviewed for extent of pulmonary artery obstruction. The coronary angiograms of 259 age- and sex-matched control patients were also examined. Among 259 CTEPH patients with definitive imaging, 34 coronary artery-pulmonary artery collaterals were found in 28 patients (10.8%), versus 1 coronary artery-pulmonary artery collateral among control subjects (0.4%; P < 0.001). Compared with CTEPH patients without collaterals, patients with collaterals had a significantly higher prevalence of total occlusion of their right or left main pulmonary artery (P < 0.001) or lobar arteries (P < 0.001). In conclusion, the prevalence of coronary artery-pulmonary artery collaterals in CTEPH patients undergoing coronary angiography for possible PTE is approximately 11%. These vessels are associated with more severe pulmonary artery occlusion. PMID:26064456

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

    PubMed Central

    Fallah, Flora

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a disease characterized by an elevation in pulmonary artery pressure that can lead to right ventricular failure and death. The pulmonary circulation has to accommodate the entire cardiac output in each cardiac cycle and evolution has adapted to this by making it a low-pressure high-flow system. However, pathology can affect both the arterial and venous components of this system. Pulmonary venous hypertension mainly refers to diseases that result in elevated venous pressure and occurs mainly from mitral valve and left-sided heart disease. Standard treatment options include oral anticoagulation, diuretics, oxygen supplementation, and for a small percentage of patients, calcium channel blockers. Newer treatments include prostacyclin analogues, endothelin receptor antago¬nists, and phosphodiesterase type 5 inhibitors. This article reviews the current treatments strategies for PAH and provides guidelines for its management. PMID:25946920

  9. Gene-environment interactions of selected pharmacogenes in arterial hypertension.

    PubMed

    Bochud, Murielle; Guessous, Idris

    2012-11-01

    Hypertension affects approximately 1 billion people worldwide. Owing to population aging, hypertension-related cardiovascular burden is expected to rise in the near future. In addition to genetic variants influencing the blood pressure response to antihypertensive drugs, several genes encoding for drug-metabolizing or -transporting enzymes have been associated with blood pressure and/or hypertension in humans (e.g., ACE, CYP1A2, CYP3A5, ABCB1 and MTHFR) regardless of drug treatment. These genes are also involved in the metabolism and transport of endogenous substances and their effects may be modified by selected environmental factors, such as diet or lifestyle. However, little is currently known on the complex interplay between environmental factors, endogenous factors, genetic variants and drugs on blood pressure control. This review will discuss the respective role of population-based primary prevention and personalized medicine for arterial hypertension, taking a pharmacogenomics' perspective focusing on selected pharmacogenes. PMID:23234325

  10. Arterial hypertension in diabetes mellitus: from theory to clinical practice.

    PubMed

    Sampanis, C; Zamboulis, C

    2008-04-01

    Diabetes mellitus and arterial hypertension are two common diseases that often coexist. Patients with diabetes have much higher rate of hypertension than that in general population. The co-existence of these disorders appears to accelerate microvascular and macrovascular complications and greatly increases the cardiovascular risk, risk of stroke and end stage renal disease. Arterial hypertension is clearly related to nephropathy in subjects with type 1 diabetes. In patients with type 2 diabetes insulin resistance seems to play a pivotal role in the pathogenesis of hypertension. Several well designed randomized controlled trials have provided evidence that patients with diabetes will benefit from a more aggressive treatment of hypertension. This benefit is seen at blood pressure level<130/80 mmHg. Moreover, most diabetic patients with hypertension require combination therapy to achieve optimal blood pressure goals. Angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, diuretics, beta-adrenoreceptor blockers and calcium- channel blockers are all effective antihypertensive agents in type 2 diabetes mellitus and no comparative trial showed the superiority of any particular class in either lowering blood pressure or reducing cardiovascular morbidity and mortality. On the basis of experimental arguments and clinical observations that have shown their apparent superiority in slowing diabetic nephropathy, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers are preferred as the first choice alone or in combination with diuretics. Second choice should be long-acting calcium-channel blockers or cardioselective beta blockers. Clinicians should be aware of the need for aggressive treatment of hypertension and spend more time in order to provide maximal benefit to the treatment of diabetes mellitus and hypertension. PMID:18923653

  11. Arterial hypertension in diabetes mellitus: from theory to clinical practice

    PubMed Central

    Sampanis, C; Zamboulis, C

    2008-01-01

    Diabetes mellitus and arterial hypertension are two common diseases that often coexist. Patients with diabetes have much higher rate of hypertension than that in general population. The co-existence of these disorders appears to accelerate microvascular and macrovascular complications and greatly increases the cardiovascular risk, risk of stroke and end stage renal disease. Arterial hypertension is clearly related to nephropathy in subjects with type 1 diabetes. In patients with type 2 diabetes insulin resistance seems to play a pivotal role in the pathogenesis of hypertension. Several well designed randomized controlled trials have provided evidence that patients with diabetes will benefit from a more aggressive treatment of hypertension. This benefit is seen at blood pressure level < 130/80 mmHg. Mopreover, most diabetic patients with hypertension require combination therapy to achieve optimal blood pressure goals. Angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, diuretics, β-adrenoreceptor blockers and calcium- channel blockers are all effective antihypertensive agents in type 2 diabetes mellitus and no comparative trial showed the superiority of any particular class in either lowering blood pressure or reducing cardiovascular morbidity and mortality. On the basis of experimental arguments and clinical observations that have shown their apparent superiority in slowing diabetic nephropathy, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers are preferred as the first choice alone or in combination with diuretics. Second choice should be long-acting calcium-channel blockers or cardioselective β blockers. Clinicians should be aware of the need for aggressive treatment of hypertension and spend more time in order to provide maximal benefit to the treatment of diabetes mellitus and hypertension. PMID:18923653

  12. [Heart failure and arterial hypertension disclosing amyloidosis].

    PubMed

    Habbal, R; Noureddine, M; Hachim, K; Zahraoui, M; Azzouzi, L; Fadouach, S; Zaid, D; Chraibi, N

    1997-01-01

    Amyloidosis results from protein infiltration of the extracellular space of organs and tissues. Several amyloidosis proteins have been identified. Protein AL, (deriving from immunoglobulin light chain), protein AA and prealbumin are the most involved in this disease. When AL amyloidosis involves the heart, the illness is often terminal. Most clinical symptoms are heart failure and arrhythmia or block conduction. This case was characterised by the unusual combination of hypertension and amyloidosis. The diagnosis suggested by the echocardiographic but was confirmed by the damaged organ's biopsy. The present case concerns a young woman, who has hypertension and a pulmonary oedema. The echocardiographic scan showed a septal hypertrophy with a shining and granite-like aspect which is compatible with heart amyloidosis. Systolic and diastolic disorder with mitral and aortic regurgitation were also revealed. The kidney and rectum biopsies confirmed amyloidosis AL of the Kappa dysglobulinemia type, without extraosseous plasmocytoma. The heart and kidney failure symptoms disappeared after treatment with diuretics and ACE inhibitors.

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

    PubMed Central

    Papathanasiou, Athanasios; Nakos, George

    2015-01-01

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

  14. 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.

  15. [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.

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

    PubMed

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

    2015-03-01

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

  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. PMID:25076995

  18. Macitentan for the treatment of pulmonary arterial hypertension.

    PubMed

    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.

  19. 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

  20. [Relevance of arterial hypertension in primary open-angle glaucoma].

    PubMed

    Erb, C; Predel, H-G

    2014-02-01

    Primary open-angle glaucoma is a multifactorial disease with a lot of different risk factors. Beside the fact that intraocular pressure (IOP) is the most important risk factor, the reduction of IOP alone is in most cases not sufficient to stop the progression of glaucoma. Therefore, other risk factors play also an important role. One of them is arterial hypertension, the most common systemic disease in glaucoma patients. Arterial hypertension increases IOP slightly, but has an important negative effect on ocular perfusion. Especially the endothelial dysfunction with a disturbed retinal autoregulation plays an important role. Therefore, ischaemic and reperfusion effects alter the optic nerve head and have negative input to the glaucomatous optic neuropathy. In future glaucoma patients should be monitored by ophthalmologists as well as by general physicians/cardiologists to optimise their treatment and to stabilise their glaucoma as well as possible.

  1. 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.

  2. 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

  3. Depression as a risk factor for arterial hypertension.

    PubMed

    Vashadze, Sh

    2011-12-01

    The aim of the subject is to represents the connection of the Arterial Hypertension and thrombocyte number in blood and to find prevention ways. A clinical case of depression symptoms as outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) is a disorder with both physical and mental characteristics that negatively disrupts an individual's ability to function day to day in social and work environments. According to the DSM, real depression is a condition of this nature that lasts for more than two weeks. The subject is actual because Arterial Hypertension according to WHO's data's is one the 1stplace, while Depression - one the 2nd.According to Georgian Disease Controlling and Medical Statistic National Centre data's, depression is characterized from 15% to 25% of people. We've searched for the clinical methods in Batumi Republic Hospital departments. 30 patient is studied by us - 15 women and 15 men. Among them, 20 patients was fallen ill with Arterial Hypertension, 5 with Ischemic insult and 5 - with Discirculating Encephalopathy. We've the question are of Beck. According to which we were able to ascertain the depression quality. The question are consists of 21 questions; by them it was possible to ascertain depression qualities light, medium and complex. The depression quality was defined as follows: the absence of depression in 13%; mild depression in 17%; medium - 30% and severe in 60%. Thus, Depression quality is very high in people with Arterial Hypertension. The number of thrombocyte is high also. Thrombocytes depression causes significant changes in the function, Thrombocytes Activation, Thrombosis increases the risk. So, it's necessary to treat this patient with Antithrombotic medicines and Antidepressants. That will contribute to solving the problem.

  4. [The cell immunity in patients with arterial hypertension and obesity].

    PubMed

    Trushina, É N; Mustafina, O K; Soto, S Kh; Bogdanov, A R; Sentsova, T B; Zaletova, T S; Kuznetsov, V D

    2012-01-01

    In the present study the relative quantity subpopulations of lymphocytes, activated T- lymphocytes and CD95-antigen (Fas/APO-1) expression on lymphocytes in the peripheral blood of patients with arterial hypertension and obesity in comparison with the healthy persons was determined. The cells were analyzed by the method of flow cytometry using Beckman Coulter FC 500 cytometer. The following of cells subsets: CD19+, CD3+, CD3+CD4+, CD3+CD8+, CD3-CD16+CD56+, CD3+CD16+CD56+, CD3+CD25+, CD3+HLA-DR+, CD45+CD95+ were investigated. In this research was establish the rise of immunoregulatory index (CD3+CD4+/CD3+CD8+) in consequence of increase the percentages of T-helper and decrease the cytotoxic T-lymphocytes in patients with arterial hypertension and obesity in comparison with the healthy persons. In the peripheral blood of patients with arterial hypertension and obesity were observed a greater level of activated T-lymphocytes (CD3+CD25+, CD3+HLA-DR+), that reflect the increase activity of T-cell immunity. In these patients a greater level of NKT-cells (CD3+CD16+CD56+) and lymphocytes expression of CD95-antigen in comparison with the healthy persons also was noted. The direct correlation between the increased quantity of T-helper lymphocytes, activated T-lymphocytes, NKT-cells, lymphocytes expression of CD95-antigen, and index of body mass in patients with arterial hypertension and obesity was found.

  5. [Pulmonary arterial hypertension, bone marrow, endothelial cell precursors and serotonin].

    PubMed

    Ayme-Dietrich, Estelle; Banas, Sophie M; Monassier, Laurent; Maroteaux, Luc

    2016-01-01

    Serotonin and bone-marrow-derived stem cells participate together in triggering pulmonary hypertension. Our work has shown that the absence of 5-HT2B receptors generates permanent changes in the composition of the blood and bone-marrow in the myeloid lineages, particularly in endothelial cell progenitors. The initial functions of 5-HT2B receptors in pulmonary arterial hypertension (PAH) are restricted to bone-marrow cells. They contribute to the differentiation/proliferation/mobilization of endothelial progenitor cells from the bone-marrow. Those bone-marrow-derived cells have a critical role in the development of pulmonary hypertension and pulmonary vascular remodeling. These data indicate that bone-marrow derived endothelial progenitors play a key role in the pathogenesis of PAH and suggest that interactions involving serotonin and bone morphogenic protein type 2 receptor (BMPR2) could take place at the level of the bone-marrow. PMID:27687599

  6. Pulmonary arterial hypertension combined with a high cardiac output state: Three remarkable cases

    PubMed Central

    Spruijt, Onno A.; Bogaard, Harm-Jan; Vonk-Noordegraaf, Anton

    2013-01-01

    A congenital extrahepatic portosystemic venous shunt (CEPVS), also known as an Abernethy malformation, is a rare cause of pulmonary arterial hypertension (PAH). In this case series, we describe three male patients of 30, 23, and 27 years of age with PAH due to a CEPVS. In all three patients, a right heart catheterization revealed a high cardiac output. The aim of this case series is to make pulmonary hypertension physicians aware of the possibility of a CEPVS when PAH is accompanied with a high cardiac output state. PMID:24015348

  7. [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. PMID:27284844

  8. [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.

  9. 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

  10. [Usefulness of Doppler ultrasound in the diagnosis of renal artery stenosis in hypertensive children. Two case reports and review of the literature].

    PubMed

    Favilli, Silvia; Capuzzo, Leila; Pollini, Iva; Calabri, Giovanni; De Simone, Luciano; Pela, Ivana; Seracini, Daniela; Bini, Roberta M

    2004-06-01

    Renal artery stenosis, mainly due to fibromuscular dysplasia, is the second more common cause of arterial hypertension in children, after aortic coarctation. Two children sent to our Center of Pediatric Cardiology, one for arterial hypertension and the other for renal failure (associated with severe hypertension not previously recognized) are reported. In both of them the diagnosis of renal artery stenosis was established at Doppler ultrasonography, performed at the time of Doppler echocardiography. Both children were submitted to successful percutaneous transluminal angioplasty; short- and medium-term results are evaluated by Doppler ultrasonography. Renovascular disease is a potentially curable cause of renal artery stenosis in children. Renal artery evaluation by Doppler ultrasound is recommended in all hypertensive children who undergo Doppler echocardiography. PMID:15471155

  11. 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

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

    PubMed

    Olowu, Wasiu Adekunle

    2015-11-01

    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 > 90(th) 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

  13. Hyponatraemic-hypertensive syndrome in a 15-month-old child with renal artery stenosis.

    PubMed

    Seracini, Daniela; Pela, Ivana; Favilli, Silvia; Bini, Roberta M

    2006-07-01

    In this report we present the case of a 15-month-old girl with hyponatraemic-hypertensive syndrome (HHS) caused by stenosis of the left renal artery. On sonographic examination the contralateral non-stenotic kidney appeared enlarged and with cortical hyperechogenicity mimicking a parenchymal lesion. After successful percutaneous transluminal angioplasty, when the girl became normotensive, her serum electrolyte and acid-base balance became normal within a few days. The contralateral non-stenotic kidney hyperechogenicity also disappeared, but only after a period of 6 months, suggesting parenchymal damage due to tubulointerstitial injury, even though reversible. Our case confirms that renovascular hypertension may rarely also be present with HHS in children and that metabolic and morphological alterations are reversible after the resolution of arterial stenosis. PMID:16773417

  14. Altered artery mechanics and structure in monocrotaline pulmonary hypertension.

    PubMed

    Langleben, D; Szarek, J L; Coflesky, J T; Jones, R C; Reid, L M; Evans, J N

    1988-11-01

    Pulmonary hypertension in rats, induced by an injection of monocrotaline, is associated with changes in the wall structure of the pulmonary arterial bed. We have studied the effects of this remodeling on mechanical properties of cylindrical pulmonary artery segments from rats 21 days after monocrotaline (MCT) injection. Resting and active (KCl induced) circumference-tension relationships were established for segments of extrapulmonary and intrapulmonary arteries isolated from the hilum and the fifth lateral branch from the axial pathway (all preacinar). The thicknesses of the vessel wall, the media, and adventitia were measured at several positions around the circumference of the artery by computerized analysis of histological cross sections of the segments fixed at a standard circumference. Resting and active stress were also calculated. The study shows that active circumferential tension and active stress are reduced in vessels from MCT-treated rats. Based on our findings, it is unlikely that altered contractile function of preacinar arteries contributes significantly to the increased vascular resistance seen in this model. PMID:3145283

  15. Arterial Stiffening Provides Sufficient Explanation for Primary Hypertension

    PubMed Central

    Pettersen, Klas H.; Bugenhagen, Scott M.; Nauman, Javaid; Beard, Daniel A.; Omholt, Stig W.

    2014-01-01

    Hypertension is one of the most common age-related chronic disorders, and by predisposing individuals for heart failure, stroke, and kidney disease, it is a major source of morbidity and mortality. Its etiology remains enigmatic despite intense research efforts over many decades. By use of empirically well-constrained computer models describing the coupled function of the baroreceptor reflex and mechanics of the circulatory system, we demonstrate quantitatively that arterial stiffening seems sufficient to explain age-related emergence of hypertension. Specifically, the empirically observed chronic changes in pulse pressure with age and the impaired capacity of hypertensive individuals to regulate short-term changes in blood pressure arise as emergent properties of the integrated system. The results are consistent with available experimental data from chemical and surgical manipulation of the cardio-vascular system. In contrast to widely held opinions, the results suggest that primary hypertension can be attributed to a mechanogenic etiology without challenging current conceptions of renal and sympathetic nervous system function. PMID:24853828

  16. Biomarkers and prognostic indicators in pulmonary arterial hypertension.

    PubMed

    Jardim, Carlos; Souza, Rogerio

    2015-06-01

    Our understanding of the pathophysiology of pulmonary arterial hypertension (PAH) has increased substantially in the past decades. More accurate diagnosis and increased options for treatment have given researchers the opportunity to better explore the response to medical therapy and prognosis. As a result, the use of biomarkers and prognostic indicators for this devastating disease has been widely investigated. Biomarkers and prognostic indicators have also been more frequently incorporated into the design of new clinical trials. This approach has helped the pulmonary hypertension (PH) community step forward in the search for effective treatments for PAH. However, no single biomarker has shown significant superiority in predicting prognosis or patient response and an integrative approach is necessary to understand which combination of markers should be used in each of the clinical scenarios that characterize the management of PAH.

  17. [Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology].

    PubMed

    Vonk-Noordegraaf, Anton; Haddad, François; Chin, Kelly M; Forfia, Paul R; Kawut, Steven M; Lumens, Joost; Naeije, Robert; Newman, John; Oudiz, Ronald J; Provencher, Steve; Torbicki, Adam; Voelkel, Norbert F; Hassoun, Paul M

    2014-10-01

    Survival in patients with pulmonary arterial hypertension (PAH) is closely related to right ventricular (RV) function. Although pulmonary load is an important determinant of RV systolic function in PAH, there remains a significant variability in RV adaptation to pulmonary hypertension. In this report, the authors discuss the emerging concepts of right heart pathobiology in PAH. More specifically, the discussion focuses on the following questions. 1) How is right heart failure syndrome best defined? 2) What are the uderlying molecular mechanisms of the failing right ventricle in PAH? 3) How are RV contractility and function and their prognostic implications best assessed? 4) What is the role of targeted RV therapy? Throughout the report, the authors highlight differences between right and left heart failure and outline key areas of future investigation. (J Am Coll Cardiol 2013;62:D22-33) a 2013 by the American College of Cardiology Foundation).

  18. Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology.

    PubMed

    Vonk-Noordegraaf, Anton; Haddad, François; Chin, Kelly M; Forfia, Paul R; Kawut, Steven M; Lumens, Joost; Naeije, Robert; Newman, John; Oudiz, Ronald J; Provencher, Steve; Torbicki, Adam; Voelkel, Norbert F; Hassoun, Paul M

    2013-12-24

    Survival in patients with pulmonary arterial hypertension (PAH) is closely related to right ventricular (RV) function. Although pulmonary load is an important determinant of RV systolic function in PAH, there remains a significant variability in RV adaptation to pulmonary hypertension. In this report, the authors discuss the emerging concepts of right heart pathobiology in PAH. More specifically, the discussion focuses on the following questions. 1) How is right heart failure syndrome best defined? 2) What are the underlying molecular mechanisms of the failing right ventricle in PAH? 3) How are RV contractility and function and their prognostic implications best assessed? 4) What is the role of targeted RV therapy? Throughout the report, the authors highlight differences between right and left heart failure and outline key areas of future investigation.

  19. Pregnancy as a possible trigger for heritable pulmonary arterial hypertension.

    PubMed

    Limoges, Maude; Langleben, David; Fox, Benjamin D; Shear, Roberta; Wieczorek, Paul; Rudski, Lawrence G; Hirsch, Andrew M; Schlesinger, Robert D; Lesenko, Lyda

    2016-09-01

    It is unclear whether pregnancy is a trigger or accelerant for idiopathic pulmonary arterial hypertension (PAH). Alternatively, its frequency close to the onset of symptoms and diagnosis in the idiopathic PAH population may represent a coincidence in a disease that predominates in young women. We describe a carrier of a BMPR2 gene mutation who had an uneventful first pregnancy but had aggressive PAH during her second pregnancy and now has ongoing heritable PAH. The possible role of pregnancy as a trigger in this vulnerable patient is discussed. Databases of patients with heritable PAH should be explored to see whether pregnancy is related to overt manifestation of the disease. PMID:27683615

  20. Pregnancy as a possible trigger for heritable pulmonary arterial hypertension

    PubMed Central

    Langleben, David; Fox, Benjamin D.; Shear, Roberta; Wieczorek, Paul; Rudski, Lawrence G.; Hirsch, Andrew M.; Schlesinger, Robert D.; Lesenko, Lyda

    2016-01-01

    Abstract It is unclear whether pregnancy is a trigger or accelerant for idiopathic pulmonary arterial hypertension (PAH). Alternatively, its frequency close to the onset of symptoms and diagnosis in the idiopathic PAH population may represent a coincidence in a disease that predominates in young women. We describe a carrier of a BMPR2 gene mutation who had an uneventful first pregnancy but had aggressive PAH during her second pregnancy and now has ongoing heritable PAH. The possible role of pregnancy as a trigger in this vulnerable patient is discussed. Databases of patients with heritable PAH should be explored to see whether pregnancy is related to overt manifestation of the disease. PMID:27683615

  1. 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. PMID:27598071

  2. Pulmonary arterial hypertension associated with neurofibromatosis type 1.

    PubMed

    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

  3. Pregnancy as a possible trigger for heritable pulmonary arterial hypertension

    PubMed Central

    Langleben, David; Fox, Benjamin D.; Shear, Roberta; Wieczorek, Paul; Rudski, Lawrence G.; Hirsch, Andrew M.; Schlesinger, Robert D.; Lesenko, Lyda

    2016-01-01

    Abstract It is unclear whether pregnancy is a trigger or accelerant for idiopathic pulmonary arterial hypertension (PAH). Alternatively, its frequency close to the onset of symptoms and diagnosis in the idiopathic PAH population may represent a coincidence in a disease that predominates in young women. We describe a carrier of a BMPR2 gene mutation who had an uneventful first pregnancy but had aggressive PAH during her second pregnancy and now has ongoing heritable PAH. The possible role of pregnancy as a trigger in this vulnerable patient is discussed. Databases of patients with heritable PAH should be explored to see whether pregnancy is related to overt manifestation of the disease.

  4. Depression in pulmonary arterial hypertension: An undertreated comorbidity

    PubMed Central

    Verma, Sameer; Sahni, Sonu; Vijayan, Vannan K; Talwar, Arunabh

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a debilitating condition leading to progressive decline in functional capacity. As a result, PAH can lead to psychological impairment that can impact the overall disease status. The medical community has developed several screening questionnaires in order to assess depression in their patients allowing physicians to be at the forefront of recognizing clinical depression. There is a suggestion that depression symptomatology is more prevalent in the PAH population. The aim of this article is to review the current thought process about diagnosis and management of depression in PAH patients. PMID:26933309

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

    PubMed

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

    2016-06-01

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

  6. 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

  7. 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

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

    PubMed

    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

  9. Role of oxidized lipids in pulmonary arterial hypertension.

    PubMed

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

    2016-09-01

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

  10. Role of oxidized lipids in pulmonary arterial hypertension.

    PubMed

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

    2016-09-01

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

  11. 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

  12. 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.

  13. Pulmonary arterial hypertension: a comparison between children and adults.

    PubMed

    Barst, R J; Ertel, S I; Beghetti, M; Ivy, D D

    2011-03-01

    The characteristics of pulmonary arterial hypertension (PAH), including pathology, symptoms, diagnosis and treatment are reviewed in children and adults. The histopathology seen in adults is also observed in children, although children have more medial hypertrophy at presentation. Both populations have vascular and endothelial dysfunction. Several unique disease states are present in children, as lung growth abnormalities contribute to pulmonary hypertension. Although both children and adults present at diagnosis with elevations in pulmonary vascular resistance and pulmonary artery pressure, children have less heart failure. Dyspnoea on exertion is the most frequent symptom in children and adults with PAH, but heart failure with oedema occurs more frequently in adults. However, in idiopathic PAH, syncope is more common in children. Haemodynamic assessment remains the gold standard for diagnosis, but the definition of vasoreactivity in adults may not apply to young children. Targeted PAH therapies approved for adults are associated with clinically meaningful effects in paediatric observational studies; children now survive as long as adults with current treatment guidelines. In conclusion, there are more similarities than differences in the characteristics of PAH in children and adults, resulting in guidelines recommending similar diagnostic and therapeutic algorithms in children (based on expert opinion) and adults (evidence-based).

  14. Arterial hypertension: which targets in over-75-year people?

    PubMed

    Mureddu, Gian Francesco

    2016-01-01

    Arterial hypertension has always been considered the main risk factor in cardiovascular prevention. However, the goals of anti-hypertensive treatment (targets) in the elderly has long been under discussion. The results of the studies in favor of the hypothesis "the lower the better" than those that argue against the existence of the phenomenon of the J-curve, that is, the hypothesis according to which mortality increases to too low pressure values lower than 115/75 mmHg, are still controversial. However, in elderly patients the association between blood pressure lowering and increased cardiovascular events seems to depend on the general health status, that means the presence of comorbidity, frailty and / or disability. Recent data from the SPRINT study show that the benefit of an intensive blood pressure target (SBP <120 mmHg) compared to a usual target (SBP <140 mmHg), appears to be greater in the oldest hypertensive patients (≥75 years). The cardio-geriatric functional assessment can provide useful information to better stratify the elderly and to define more accurately the pressure targets, the choice is individual. PMID:27374038

  15. Arterial lesions and hypertension induced by saline, unilateral nephrectomy, and deoxycorticosterone in spontaneously hypertensive SHR rats.

    PubMed

    Wexler, B C

    1979-07-01

    Male and female, 100 days old, spontaneously hypertensive rats (SHR) were divided into two major groups: intact and uninephrectomized, given either no treatment, 1p.100 saline drinking water, 1p.100 saline + Deoxycorticosterone (DOC), or DOC alone. The DOC (Percorten pivalate) was given subcutaneously 2 times weekly, at a dose level of 2 mg/rat for 8 weeks. At autopsy, the combination of DOC + saline caused: the greatest exacerbation of blood pressure, marked catabolism, adrenal hypertrophy and thymic involution, little increase in heart weight, but a marked increase in kidney weight, elevated triglyceride and free fatty acids, cerebral and myocardial necrosis, fibrinous hyalinization of the cerebral, coronary, mesenteric, renal, testicular and ovarian arteries, foci of aortic cartilaginous metaplasia, PAN, foci of hepatic necrosis, and extensive lipid depletion from the zonae glomerulosa. Circulating corticosterone levels were suppressed to below normal levels. Excursion of circulating CPK levels coincided with the finding of myocardial necrosis and cerebral damage. It is suggested that the genetically-mediated hypertension of SHR is programmed through abnormal activity of the hypothalamic-pituitary axis and the specific morphologic make-up of arterial lesions is dependent upon the variety of adrenal or gonadal steroids secreted and their conditioning effect on the arterial wall.

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2016-04-01

    Pulmonary arteriovenous fistulas (PAVFs) are rare. Diffuse type PAVFs with pulmonary arterial hypertension (PAH) are even rarer and can elude anatomy imaging like a plain chest film or a computed tomography. The rapid blood flow that ensues due to lack of a capillary bed leads to various degrees of ischemia depending on the number and size of the PAVF. This is a case report of diffuse PAVF in a patient with PAH.This case report describes a patient with recurrent hemoptysis and chest pain. Systemic examination was unremarkable except for P2 attenuation on auscultation. Echocardiograghy showed confirmed pulmonary hypertension with mild dilation of right atrium and ventricle and a tricuspid regurgitation pressure gradient of 40 mm Hg and ruled out congenital heart diseases. Right heart catheterization revealed precapillary PAH with mean pulmonary arterial pressure of 88 mm Hg. Pulmonary angiography showed enlarged pulmonary arterial trunk and diffuse spiral tortuous pulmonary arterial branches indicting diffuse PAVFs. The patient was diagnosed as PAH and began treatment of 25 mg tid of sildenafil.The case highlights a rare and unique presentation of PAH. PMID:27057843

  18. Impact of residual stretch and remodeling on collagen engagement in healthy and pulmonary hypertensive calf pulmonary arteries at physiological pressures.

    PubMed

    Tian, Lian; Lammers, Steven R; Kao, Philip H; Albietz, Joseph A; Stenmark, Kurt R; Qi, H Jerry; Shandas, Robin; Hunter, Kendall S

    2012-07-01

    Understanding the mechanical behavior of proximal pulmonary arteries (PAs) is crucial to evaluating pulmonary vascular function and right ventricular afterload. Early and current efforts focus on these arteries' histological changes, in vivo pressure-diameter behavior and mechanical properties under in vitro mechanical testing. However, the in vivo stretch and stress states remain poorly characterized. To further understand the mechanical behavior of the proximal PAs under physiological conditions, this study computed the residual stretch and the in vivo circumferential stretch state in the main pulmonary arteries in both control and hypertensive calves by using in vitro and in vivo artery geometry data, and modeled the impact of residual stretch and arterial remodeling on the in vivo circumferential stretch distribution and collagen engagement in the main pulmonary artery. We found that the in vivo circumferential stretch distribution in both groups was nonuniform across the vessel wall with the largest stretch at the outer wall, suggesting that collagen at the outer wall would engage first. It was also found that the circumferential stretch was more uniform in the hypertensive group, partially due to arterial remodeling that occurred during their hypoxic treatment, and that their onset of collagen engagement occurred at a higher pressure. It is concluded that the residual stretch and arterial remodeling have strong impact on the in vivo stretch state and the collagen engagement and thus the mechanical behavior of the main pulmonary artery in calves. PMID:22237861

  19. [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.

  20. [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. PMID:27172721

  1. [Role of arterial hypertension in the cardiac involvement of acromegaly].

    PubMed

    Morvan, D; Komajda, M; Grimaldi, A; Turpin, G; Grosgogeat, Y

    1990-09-01

    Cardiac disease is common in acromegaly. Several mechanisms have been implicated: hypertension, coronary artery disease, valvular heart disease, endocrinopathies including "acromegalic cardiomyopathy". Fifteen consecutive patients with acromegaly, aged 48 +/- 13 years and treated for 4 +/- 5 years, underwent Doppler echocardiography. The patients had no cardiovascular symptoms: 6 had hypertension for 10 +/- 7 years and were compared with a group of 10 control subjects of the same age (48 +/- 17 years). The myocardial mass index (MMI) was higher in acromegaly (110 +/- 32 vs 82 +/- 12 g/m2, p = 0.02), left ventricular enddiastolic dimensions where comparable (48 +/- 7 vs 48 +/- 5 mm, NS) fractional shortening was slightly greater (0.37 +/- 0.04 vs 0.34 +/- 0.04, p = 0.07) as was velocity of shortening (NS) and the ratio of systolic time intervals (NS). The mitral EF slope was decreased (80 +/- 21 vs 101 +/- 30 ms; p less than 0.02); the ratio of the amplitudes of the E and A waves was a little decreased and the isovolumic relaxation phase was increased (92 +/- 13 vs 69 +/- 16 ms; p less than 0.01). Hypertensives (N = 6) had higher MMI (133 +/- 27 vs 94 +/- 24 g/m2, p = 0.02). Normotensive patients had larger isovolumic relaxation periods than control subjects (90 +/- 11 vs 69 +/- 16 ms, p less than 0.05). These results show that in the infraclinical phase, the heart in acromegaly is hypertrophied, not dilated. Hypertension plays a significant role in the development of this hypertrophy. Left ventricular systolic function is normal but diastolic function is impaired.

  2. 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.

  3. 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

  4. Versican accumulates in vascular lesions in pulmonary arterial hypertension.

    PubMed

    Chang, Ya-Ting; 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

    2016-09-01

    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 [(35)S]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

  5. 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.

  6. 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

  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. [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

  9. 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

  10. 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

  11. Psychosocial Burdens of Pulmonary Arterial Hypertension: A Discussion Paper.

    PubMed

    Doyle-Cox, Carolyn; Brousseau, Carolynne; Tulloch, Heather; Mielniczuk, Lisa M; Davies, Ross A; Sherrard, Heather; Clark, Lorraine

    2016-01-01

    Pulmonary arterial hypertension is an uncommon and devastating chronic illness with no known cure. Little is known about the disease, and even less about the psychosocial burdens. While it is important to create awareness about the physical aspects of the disease, it is equally important to create awareness about the psychosocial burdens patients and their families face. We reviewed the literature to better understand these psychosocial burdens, which include impact from physical limitations, emotional strains, financial burdens, social isolation, lack of intimacy in relationships, and an overall lack of information. The findings can be used to assist health care providers to understand the psychosocial challenges that are being experienced by patients and families in order to better provide supportive care. The creation of a standardized tool to assess the psychosocial burdens at each clinic visit can benefit health care providers by addressing challenges faced and facilitate subsequent referral to appropriate specialists.

  12. Macitentan for the treatment of pulmonary arterial hypertension.

    PubMed

    DuBrock, Hilary M; Channick, Richard N

    2014-08-01

    Macitentan is a novel dual endothelin receptor antagonist recently approved for the treatment of symptomatic pulmonary arterial hypertension (PAH). Compared to other endothelin receptor antagonists, in vitro and in vivo studies have demonstrated that macitentan has improved tissue targeting, a longer duration of action and an improved safety profile. Macitentan is available as a once daily oral medication and has been well tolerated in clinical trials. The recently published Study with an Endothelin Receptor Antagonist in PAH to Improve cliNical Outcomes (SERAPHIN), which was the first event-driven trial ever done in PAH, also demonstrated the benefit of macitentan on reducing the likelihood of a composite endpoint of morbidity and mortality events without a significant difference in mortality.

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

    PubMed

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

    2014-07-01

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

  14. Connective tissue disease-related pulmonary arterial hypertension.

    PubMed

    Thakkar, Vivek; Lau, Edmund M T

    2016-02-01

    Over the past two decades, there have been several advances in the assessment and management of connective tissue disease-related pulmonary arterial hypertension (CTD-PAH) that improved outcomes of the treatment of this lethal disease, and this will be the focus of this study. Systemic sclerosis is the leading cause of CTD-PAH, followed by systemic lupus erythematosus, mixed connective tissue disease, idiopathic inflammatory myositis, rheumatoid arthritis, and Sjogren's syndrome. Clinical registries have been invaluable in informing about the burden of disease, risk and prognostic factors, and temporal trends with respect to treatment and outcome in CTD-PAH. The major advances have centered on improved disease classification and diagnostic criteria, screening and early diagnosis, the emergence of evidence-based therapies including combination goal-orientated treatment strategies, and the establishment of centers with expertise in PAH.

  15. Connective tissue disease-related pulmonary arterial hypertension.

    PubMed

    Thakkar, Vivek; Lau, Edmund M T

    2016-02-01

    Over the past two decades, there have been several advances in the assessment and management of connective tissue disease-related pulmonary arterial hypertension (CTD-PAH) that improved outcomes of the treatment of this lethal disease, and this will be the focus of this study. Systemic sclerosis is the leading cause of CTD-PAH, followed by systemic lupus erythematosus, mixed connective tissue disease, idiopathic inflammatory myositis, rheumatoid arthritis, and Sjogren's syndrome. Clinical registries have been invaluable in informing about the burden of disease, risk and prognostic factors, and temporal trends with respect to treatment and outcome in CTD-PAH. The major advances have centered on improved disease classification and diagnostic criteria, screening and early diagnosis, the emergence of evidence-based therapies including combination goal-orientated treatment strategies, and the establishment of centers with expertise in PAH. PMID:27421214

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

    PubMed

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

    2013-12-24

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

  17. Psychosocial Burdens of Pulmonary Arterial Hypertension: A Discussion Paper.

    PubMed

    Doyle-Cox, Carolyn; Brousseau, Carolynne; Tulloch, Heather; Mielniczuk, Lisa M; Davies, Ross A; Sherrard, Heather; Clark, Lorraine

    2016-01-01

    Pulmonary arterial hypertension is an uncommon and devastating chronic illness with no known cure. Little is known about the disease, and even less about the psychosocial burdens. While it is important to create awareness about the physical aspects of the disease, it is equally important to create awareness about the psychosocial burdens patients and their families face. We reviewed the literature to better understand these psychosocial burdens, which include impact from physical limitations, emotional strains, financial burdens, social isolation, lack of intimacy in relationships, and an overall lack of information. The findings can be used to assist health care providers to understand the psychosocial challenges that are being experienced by patients and families in order to better provide supportive care. The creation of a standardized tool to assess the psychosocial burdens at each clinic visit can benefit health care providers by addressing challenges faced and facilitate subsequent referral to appropriate specialists. PMID:27159936

  18. 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.

  19. [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.

  20. 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

  1. An international physician survey of pulmonary arterial hypertension management.

    PubMed

    Preston, Ioana R; Hinzmann, Barbara; Heinz, Sabina; Gall, Henning; Jenkins, David; Kim, Nick H; Lang, Irene

    2016-09-01

    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.

  2. Epigenetic modulation as a therapeutic approach for pulmonary arterial hypertension

    PubMed Central

    Kim, Jun-Dae; Lee, Aram; Choi, Jihea; Park, Youngsook; Kang, Hyesoo; Chang, Woochul; Lee, Myeong-Sok; Kim, Jongmin

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a rare but progressive and currently incurable disease, which is characterized by vascular remodeling in association with muscularization of the arterioles, medial thickening and plexiform lesion formation. Despite our advanced understanding of the pathogenesis of PAH and the recent therapeutic advances, PAH still remains a fatal disease. In addition, the susceptibility to PAH has not yet been adequately explained. Much evidence points to the involvement of epigenetic changes in the pathogenesis of a number of human diseases including cancer, peripheral hypertension and asthma. The knowledge gained from the epigenetic study of various human diseases can also be applied to PAH. Thus, the pursuit of novel therapeutic targets via understanding the epigenetic alterations involved in the pathogenesis of PAH, such as DNA methylation, histone modification and microRNA, might be an attractive therapeutic avenue for the development of a novel and more effective treatment. This review provides a general overview of the current advances in epigenetics associated with PAH, and discusses the potential for improved treatment through understanding the role of epigenetics in the development of PAH. PMID:26228095

  3. Epigenetic modulation as a therapeutic approach for pulmonary arterial hypertension.

    PubMed

    Kim, Jun-Dae; Lee, Aram; Choi, Jihea; Park, Youngsook; Kang, Hyesoo; Chang, Woochul; Lee, Myeong-Sok; Kim, Jongmin

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a rare but progressive and currently incurable disease, which is characterized by vascular remodeling in association with muscularization of the arterioles, medial thickening and plexiform lesion formation. Despite our advanced understanding of the pathogenesis of PAH and the recent therapeutic advances, PAH still remains a fatal disease. In addition, the susceptibility to PAH has not yet been adequately explained. Much evidence points to the involvement of epigenetic changes in the pathogenesis of a number of human diseases including cancer, peripheral hypertension and asthma. The knowledge gained from the epigenetic study of various human diseases can also be applied to PAH. Thus, the pursuit of novel therapeutic targets via understanding the epigenetic alterations involved in the pathogenesis of PAH, such as DNA methylation, histone modification and microRNA, might be an attractive therapeutic avenue for the development of a novel and more effective treatment. This review provides a general overview of the current advances in epigenetics associated with PAH, and discusses the potential for improved treatment through understanding the role of epigenetics in the development of PAH. PMID:26228095

  4. 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.

  5. An international physician survey of pulmonary arterial hypertension management.

    PubMed

    Preston, Ioana R; Hinzmann, Barbara; Heinz, Sabina; Gall, Henning; Jenkins, David; Kim, Nick H; Lang, Irene

    2016-09-01

    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

  6. [Drug therapy of pulmonary arterial hypertension in 2014].

    PubMed

    Aschermann, Michael; Jansa, Pavel

    2014-04-01

    Pulmonary arterial hypertension (PAH) is a primary pulmonary arteriolar disease, characterized by a progressive increase in pulmonary vascular resistance and pressure in the pulmonary circulation. It progressively leads to hypertrophy of the right ventricle and with no treatment to its failure and patient´s death. Etiology of pulmonary hypertension (PH) has been reclassified repeatedly, most recently during the 4th World Symposium on Pulmonary Hypertension held in 2008 [1]. Currently, the first group contains PAH with either unknown or known cause (systemic connective tissue disease, liver disease, congenital heart disease, HIV infection, abuse of anorexic agents). Current drug therapy of PAH is divided into conventional (anticoagulant therapy, calcium channel blockers, therapy of chronic heart failure) and specific (prostanoids, endothelium receptor antagonists, phosphodiesterase 5 inhibitors). Patients with positive vasodilator test are indicated for the high doses treatment of calcium channel blockers. Patients with negative vasodilator test are indicated for chronic anticoagulant therapy and specific drug therapy either as mono-therapy, or as combined therapy. Recent years have brought a wide range of new treatments modalities, especially in the field of pharmacotherapy. In addition, other treatment modalities have been tested, for example application of stem cells. Drugs in research include several groups: 1. vasodilators: fasudil, adrenonedullin, activators and stimulators of guanylate cyclase, vasoactive intestinal peptide (VIP); 2. Anti-inflammatory agents: inhibitor of elastase, antagonist of B cells, immunosuppressive agents, inhibitor of HDAC1; 3. agents affecting metabolism: nitrites, PPAR antagonists, antioxidants, serotonin receptor antagonist and serotonin transporter blockers, statins, inhibitors of Rho-kinase; 4. apoptosis inductors of smooth muscle cells: tyrosine-kinase inhibitors, elastase inhibitors; 5. agents influencing vascular regeneration

  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. 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. PMID:25251989

  9. 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. PMID:6839814

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

    PubMed Central

    Liu, Qian-Qian; Jing, Zhi-Cheng

    2015-01-01

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

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

    PubMed

    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

  12. 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

  13. Comparative Effectiveness of Oral Medications for Pulmonary Arterial Hypertension.

    PubMed

    Igarashi, Ataru; Inoue, Sachie; Ishii, Tomonori; Tsutani, Kiichiro; Watanabe, Hiroshi

    2016-07-27

    Pulmonary arterial hypertension (PAH) is a disease that imposes a significant burden on patients. Although multiple treatment options for PAH are available, head-to-head comparisons are difficult to conduct. Network meta-analysis (NMA) can be a useful alternative for direct comparison to estimate the relative effectiveness of multiple treatments. The objective of the present study was to conduct a systematic review and NMA to evaluate the relative effectiveness among oral PAH medications.Data collection was performed by searching the Cochrane Central Register of Controlled Trials (CENTRAL) and Ichushi-Web. Randomized controlled trials (RCTs) assessing at least 1 of the following 3 outcome measurements; 6-minute walk distance test (6MWD), WHO functional class (WHOFC), and mean pulmonary artery pressure (mPAP) were included (PROSPERO registration number: CRD42015016557). Outcomes were evaluated by estimating the differences in the mean change from baseline or by estimating the odds ratios. Analyses were performed using WinBUGS 1.4.3.Seven double-blind RCTs were eligible. NMA results showed similar improvements in 6MWD for all medications assessed. Bosentan and sildenafil caused a statistically significant improvement in WHOFC compared to other medications.The relative effectiveness of oral PAH medications could be compared using NMA, which suggested the superiority of bosentan and sildenafil in the improvement of WHOFC. PMID:27385603

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

    PubMed

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

    2013-09-01

    Pulmonary arterial hypertension (PAH) is a rare disorder characterised by progressive obliteration of the pulmonary microvasculature resulting in elevated pulmonary vascular resistance and premature death. According to the current classification PAH can be associated with exposure to certain drugs or toxins, particularly to appetite suppressant intake drugs, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market. The supposed mechanism is an increase in serotonin levels, which was demonstrated to act as a growth factor for the pulmonary artery smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used, but are considered possible risk factors, for PAH. Dasatinib, dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, potentially in part reversible after dasatinib withdrawal. Recently, several studies have raised the issue of potential endothelial dysfunction that could be induced by interferon, and a few cases of PAH have been reported with interferon therapy. PAH remains a rare complication of these drugs, suggesting possible individual susceptibility, and further studies are needed to identify patients at risk of drug-induced PAH. PMID:23997051

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

    PubMed

    Liu, Qian-Qian; Jing, Zhi-Cheng

    2015-01-01

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

  16. Imatinib in pulmonary arterial hypertension: c-Kit inhibition.

    PubMed

    Farha, Samar; Dweik, Raed; Rahaghi, Franck; Benza, Raymond; Hassoun, Paul; Frantz, Robert; Torres, Fernando; Quinn, Deborah A; Comhair, Suzy; Erzurum, Serpil; Asosingh, Kewal

    2014-09-01

    Pulmonary arterial hypertension (PAH) is a progressive disease characterized by severe remodeling of the pulmonary artery resulting in increased pulmonary artery pressure and right ventricular hypertrophy and, ultimately, failure. Bone marrow-derived progenitor cells play a critical role in vascular homeostasis and have been shown to be involved in the pathogenesis of PAH. A proliferation of c-Kit(+) hematopoietic progenitors and mast cells has been noted in the remodeled vessels in PAH. Imatinib, a tyrosine kinase inhibitor that targets c-Kit, has been shown to be beneficial for patients with PAH. Here we hypothesize that the clinical benefit of imatinib in PAH could be related to c-Kit inhibition of progenitor cell mobilization and maturation into mast cells. As a corollary to the phase 3 study using imatinib in PAH, blood samples were collected from 12 patients prior to starting study drug (baseline) and while on treatment at weeks 4 and 24. Eight were randomized to imatinib and 4 to placebo. Circulating c-Kit(+) and CD34(+)CD133(+) hematopoietic progenitors as well as biomarkers of mast cell numbers and activation were measured. Circulating CD34(+)CD133(+) and c-Kit(+) progenitor cells as well as c-Kit(+)/CD34(+)CD133(+) decreased with imatinib therapy (all P < 0.05). In addition, total tryptase, a marker of mast cell load, dropped with imatinib therapy (P = 0.02) and was related to pulmonary vascular resistance (R = 0.7, P = 0.02). The findings support c-Kit inhibition as a potential mechanism of action of imatinib in PAH and suggest that tryptase is a potential biomarker of response to therapy. PMID:25621158

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

    PubMed

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

    2014-02-01

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

  18. [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. PMID:12852007

  19. 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.

  20. 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. PMID:27456526

  1. 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

  2. Vertebrojugular arteriovenous fistula and pseudoaneurysm formation due to penetrating vertebral artery injury: case report and review of the literature.

    PubMed

    Yilmaz, Muhammet Bahadır; Donmez, Halil; Tonge, Mehmet; Senol, Serkan; Tekiner, Ayhan

    2015-01-01

    Vertebral artery injury including thrombosis, arteriovenous fistula (AVF), pseudo-aneurysm and hemorrhage may be iatrogenic or due to penetrating or blunt trauma. Although mostly asymptomatic, vertebral artery injury may also present with vertebrobasilar insufficiency findings, cephalgia, radicular pain or myelopathy due to blockade of arterial flow, arterial steal phenomenon and venous hypertension. The gold standard for diagnosis is digital subtraction angiography (DSA). Doppler ultrasonography, magnetic resonance-angiography and computerized tomography-angiography are also helpful. Endovascular treatment is now used more commonly. We present a case with sharp bread knife injury of the vertebral artery that was also complicated with a vertebrojugular fistula and pseudo-aneurysm together with the diagnostic and management options and a review of the current literature. PMID:25640560

  3. Soluble Guanylate Cyclase: A new therapeutic target for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

    PubMed Central

    Das Gupta, Asish; Bowman, Lindsay; D’Arsigny, Christine L.; Archer, Stephen L.

    2014-01-01

    Nitric oxide (NO) activates soluble guanylate cyclase (sGC) by binding its prosthetic heme group, thereby catalyzing cyclic guanosine monophosphate (cGMP) synthesis. cGMP causes vasodilation and may inhibit smooth muscle cell proliferation and platelet aggregation. The NO-sGC-cGMP pathway is disordered in pulmonary arterial hypertension (PAH), a syndrome in which pulmonary vascular obstruction, inflammation, thrombosis, and constriction ultimately lead to death from right heart failure. Expression of sGC is increased in PAH but its function is reduced by decreased NO bioavailability, sGC oxidation and the related loss of sGC’s heme group. Two classes of sGC modulators offer promise in PAH. sGC stimulators (e.g. riociguat) require heme-containing sGC to catalyze cGMP production, whereas sGC activators (e.g. cinaciguat) activate heme-free sGC. Riociguat is approved for PAH and yields functional and hemodynamic benefits similar to other therapies. Its main serious adverse effect is dose-dependent hypotension Riociguat is also approved for inoperable chronic thromboembolic pulmonary hypertension. PMID:25670386

  4. Information experiences and needs in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension.

    PubMed

    Ivarsson, Bodil; Ekmehag, Björn; Sjöberg, Trygve

    2014-01-01

    Background. Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are fatal, noncurable, but treatable diseases that strongly affect the patients. Objective. To describe patients' experience of information relating to PAH or CTEPH. Methods. A qualitative method using content analysis was applied. Seventeen patients (thirteen women and four men) aged 28-73 years from a regional PAH centre were individually interviewed. Results. Three categories that describe patients' experiences of information emerged: handling of information, struggling with feelings that also affect others, and vulnerability associated with uncertainty. The patients would have welcomed more information to relatives from the healthcare professionals. Shortcomings on communicating a prognosis were experienced. The mediated information and knowledge gave the patients insight into physical or psychosocial problems. Mutual exchange of information between patients and healthcare professionals were marred by different experiences of attitudes, behaviour, and ownership. Conclusions. In the future, healthcare organizations must struggle to achieve a holistic healthcare by making it more person-centred, and they must also promote cooperation between PAH centres and local healthcare providers. It is essential to determine the most appropriate and valuable path of information and communication and, thereby, the most cost-effective management of PAH or CTEPH. PMID:25197567

  5. Copper Dependence of Angioproliferation in Pulmonary Arterial Hypertension in Rats and Humans

    PubMed Central

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

    2012-01-01

    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. PMID:22162909

  6. 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

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

    PubMed Central

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

    2015-01-01

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

  8. 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.

  9. 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.

  10. Updated Evidence-Based Treatment Algorithm in Pulmonary Arterial Hypertension

    PubMed Central

    Barst, Robyn J.; Gibbs, J. Simon; Ghofrani, Hossein A.; Hoeper, Marius M.; McLaughlin, Vallerie V.; Rubin, Lewis J.; Sitbon, Olivier; Tapson, Victor; Galiè, Nazzareno

    2009-01-01

    Uncontrolled and controlled clinical trials with different compounds and procedures are reviewed to define the risk-benefit profiles for therapeutic options in pulmonary arterial hypertension (PAH). A grading system for the level of evidence of treatments based on the controlled clinical trials performed with each compound is used to propose an evidence-based treatment algorithm. The algorithm includes drugs approved by regulatory agencies for the treatment of PAH and/or drugs available for other indications. The different treatments have been evaluated mainly in idiopathic PAH, heritable PAH, and in PAH associated with the scleroderma spectrum of diseases or with anorexigen use. Extrapolation of these recommendations to other PAH subgroups should be done with caution. Oral anticoagulation is proposed for most patients; diuretic treatment and supplemental oxygen are indicated in cases of fluid retention and hypoxemia, respectively. High doses of calcium channel blockers are indicated only in the minority of patients who respond to acute vasoreactivity testing. Nonresponders to acute vasoreactivity testing, or responders who remain in World Health Organization (WHO) functional class III, should be considered candidates for treatment with either an oral phosphodiesterase-5 inhibitor or an oral endothelin-receptor antagonist. Continuous intravenous administration of epoprostenol remains the treatment of choice in WHO functional class IV patients. Combination therapy is recommended for patients treated with PAH monotherapy who remain in New York Heart Association functional class III. Atrial septostomy and lung transplantation are indicated for refractory patients or where medical treatment is unavailable. PMID:19555861

  11. Development of macitentan for the treatment of pulmonary arterial hypertension.

    PubMed

    Selej, Mona; Romero, Alain J; Channick, Richard N; Clozel, Martine

    2015-11-01

    Pulmonary arterial hypertension (PAH) is a serious, chronic condition that, without early recognition and treatment, leads to progressive right heart failure and death. The dual endothelin receptor antagonist macitentan was designed through a deliberate discovery process to maximize endothelin-axis blockade while improving adverse-effect profiles compared with previous compounds. Macitentan's efficacy was demonstrated in an event-driven morbidity and mortality study of treatment-naive and background PAH therapy-treated symptomatic patients. Compared to placebo, 10 mg of macitentan significantly reduced the relative risk of morbidity and mortality by 45%, primarily by delaying PAH worsening, most prominently in World Health Organization (WHO) functional class II and III PAH patients. Macitentan reduced the incidence of the composite end point of PAH-related hospitalizations and mortality and improved WHO FC and exercise capacity (6-min walk distance). Furthermore, it significantly improved cardiopulmonary hemodynamics and quality of life, and had a favorable safety and tolerability profile. To date, this was the largest and longest prospective trial for PAH. Macitentan, currently the only approved oral PAH treatment shown to be safe and effective in delaying long-term progression and reducing PAH-related hospitalizations, has changed treatment paradigms from goal-directed to long-term outcome-oriented therapy.

  12. 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

  13. 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

  14. Connective tissue disease-associated pulmonary arterial hypertension

    PubMed Central

    Howard, Luke S.

    2015-01-01

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

  15. Apoptosis-based therapy to treat pulmonary arterial hypertension

    PubMed Central

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

    2016-01-01

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

  16. 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

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

    PubMed Central

    2015-01-01

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

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

    PubMed

    Fessel, Joshua P; West, James D

    2015-12-01

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

  19. 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

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

    PubMed

    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

  1. [Early digitalisation of patients with arterial hypertension (author's transl)].

    PubMed

    Nechwatal, W; König, E; Eversmann, A; Lehnert, J

    1977-07-01

    Haemodynamic tests were performed at rest and during exercise in 41 patients with arterial hypertension and early impairment of left-ventricular function, before and after administration of a single dose of 0.6 mg beta-methyl-digoxin. After clinical, ECG and coronary-angiographic studies, the patients were assigned to two groups. Group I: 17 patients with transmural infarcts in the chronic stage or with angina. Cardiac output was within normal limits at rest and on exercise and was not significantly altered by administration of beta-methyl-digoxin. There was no significant fall during exercise of the abnormally elevated pulmonary "wedge" pressure or of other pressures in the lesser circulation after digitalis. Group II: 24 patients without signs of coronary heart disease. They, too, had a normal cardiac output at rest and on exercise, not significantly changed by digitalisation with beta-methyl-digoxin. But pulmonary "wedge" pressure and right-atrial mean pressure were significantly reduced during exercise. Before beta-methyl-digoxin the mean "wedge" pressure rose on exercise to an average of 27.3 +/- 5.4 mm Hg, but after beta-methyl-digoxin to only 21.7 +/- 5.1 mm Hg (P less than 0.001). The mean right atrial pressure changed similar. These results indicate that acute digitalisation at the stated dosage in general has an effect on abnormal myocardial function only if there is no additional coronary heart disease. PMID:880903

  2. [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. PMID:26047999

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

    PubMed

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

    2016-06-01

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

  4. [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.

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

    PubMed Central

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

    2014-01-01

    Persistent pulmonary hypertension of the newborn (PPHN) is a clinical syndrome that is characterized by high pulmonary vascular resistance due to changes in lung vascular growth, structure, and tone. PPHN has been primarily considered as a disease of the small pulmonary arteries (PA), but proximal vascular stiffness has been shown to be an important predictor of morbidity and mortality in other diseases associated with pulmonary hypertension (PH). The objective of this study is to characterize main PA (MPA) stiffness in experimental PPHN and to determine the relationship of altered biomechanics of the MPA with changes in extracellular matrix (ECM) content and orientation of collagen and elastin fibers. MPAs were isolated from control and PPHN fetal sheep model and were tested by planar biaxial testing to measure stiffness in circumferential and axial vessel orientations. Test specimens were fixed for histological assessments of the vascular wall ECM constituents collagen and elastin. MPAs from PPHN sheep had increased mechanical stiffness (P < 0.05) and altered ECM remodeling compared with control MPA. A constitutive mathematical model and histology demonstrated that PPHN vessels have a smaller contribution of elastin and a greater role for collagen fiber engagement compared with the control arteries. We conclude that exposure to chronic hemodynamic stress in late-gestation fetal sheep increases proximal PA stiffness and alters ECM remodeling. We speculate that proximal PA stiffness further contributes to increased right ventricular impedance in experimental PPHN, which contributes to abnormal transition of the pulmonary circulation at birth. PMID:25326575

  6. Effect of Leonurus cardiaca oil extract in patients with arterial hypertension accompanied by anxiety and sleep disorders.

    PubMed

    Shikov, Alexander N; Pozharitskaya, Olga N; Makarov, Valery G; Demchenko, Dmitry V; Shikh, Evgenia V

    2011-04-01

    Leonurus cardiaca L. (Lamiaceae) is used traditionally for its sedative, hypotensive and cardiotonic effects. Due to the lack of clinical data regarding its effect in patients, a study was carried out to assess the clinical efficacy of Leonurus oil extract (LOE) in patients with arterial hypertension stages 1 and 2, accompanied by anxiety and sleep disorders. Fifty patients were treated for 28 days with 1200 mg LOE per day. Positive effects of LOE on psycho-emotional status and arterial blood pressure in patients with stage 1 hypertension were observed 1 week earlier than in patients with stage 2 hypertension. According to the Clinical Global Impression (CGI) scale, a significant improvement in the symptoms of anxiety and depression was observed in 32% of patients, a moderate improvement in 48% and a weak effect in 8%; 12% of patients did not respond to therapy. Side effects were minimal in all groups. Leonurus oil extract may therefore be a potentially effective therapeutic agent for patients with arterial hypertension and concurrent psycho-neurological disorders.

  7. Effect of Leonurus cardiaca oil extract in patients with arterial hypertension accompanied by anxiety and sleep disorders.

    PubMed

    Shikov, Alexander N; Pozharitskaya, Olga N; Makarov, Valery G; Demchenko, Dmitry V; Shikh, Evgenia V

    2011-04-01

    Leonurus cardiaca L. (Lamiaceae) is used traditionally for its sedative, hypotensive and cardiotonic effects. Due to the lack of clinical data regarding its effect in patients, a study was carried out to assess the clinical efficacy of Leonurus oil extract (LOE) in patients with arterial hypertension stages 1 and 2, accompanied by anxiety and sleep disorders. Fifty patients were treated for 28 days with 1200 mg LOE per day. Positive effects of LOE on psycho-emotional status and arterial blood pressure in patients with stage 1 hypertension were observed 1 week earlier than in patients with stage 2 hypertension. According to the Clinical Global Impression (CGI) scale, a significant improvement in the symptoms of anxiety and depression was observed in 32% of patients, a moderate improvement in 48% and a weak effect in 8%; 12% of patients did not respond to therapy. Side effects were minimal in all groups. Leonurus oil extract may therefore be a potentially effective therapeutic agent for patients with arterial hypertension and concurrent psycho-neurological disorders. PMID:20839214

  8. Pulmonary artery endothelium resident endothelial colony-forming cells in pulmonary arterial hypertension

    PubMed Central

    Duong, Heng T.; Comhair, Suzy A.; Aldred, Micheala A.; Mavrakis, Lori; Savasky, Benjamin M.; Erzurum, Serpil C.; Asosingh, Kewal

    2011-01-01

    Proliferative pulmonary vascular remodeling is the pathologic hallmark of pulmonary arterial hypertension (PAH) that ultimately leads to right heart failure and death. Highly proliferative endothelial cells known as endothelial colony-forming cells (ECFC) participate in vascular homeostasis in health as well as in pathological angiogenic remodeling in disease. ECFC are distinguished by the capacity to clonally proliferate from a single cell. The presence of ECFC in the human pulmonary arteries and their role in PAH pathogenesis is largely unknown. In this study, we established a simple technique for isolating and growing ECFC from cultured pulmonary artery endothelial cells (PAEC) to test the hypothesis that ECFC reside in human pulmonary arteries and that the proliferative vasculopathy of PAH is related to greater numbers and/or more proliferative ECFC in the pulmonary vascular wall. Flow cytometric forward and side scatter properties and aggregate correction were utilized to sort unmanipulated, single PAEC to enumerate ECFC in primary PAEC cultures derived from PAH and healthy lungs. After 2 weeks, wells were assessed for ECFC formation. ECFC derived from PAH PAEC were more proliferative than control. A greater proportion of PAH ECFC formed colonies following subculturing, demonstrating the presence of more ECFC with high proliferative potential among PAH PAEC. Human androgen receptor assay showed clonality of progeny, confirming that proliferative colonies were single cell-derived. ECFC expressed CD31, von Willebrand factor, endothelial nitric oxide synthase, caveolin-1 and CD34, consistent with an endothelial cell phenotype. We established a simple flow cytometry method that allows ECFC quantification using unmanipulated cells. We conclude that ECFC reside among PAEC and that PAH PAEC contain ECFC that are more proliferative than ECFC in control cultures, which likely contributes to the proliferative angiopathic process in PAH. PMID:22530103

  9. 5-Hydroxytryptamine receptors mediating vasoconstriction in pulmonary arteries from control and pulmonary hypertensive rats.

    PubMed Central

    MacLean, M. R.; Sweeney, G.; Baird, M.; McCulloch, K. M.; Houslay, M.; Morecroft, I.

    1996-01-01

    1. We investigated 5-hydroxytryptamine (5-HT)-receptor mediated vasoconstriction in the main, first branch and resistance pulmonary arteries removed from control and pulmonary hypertensive rats. Contractile responses to 5-HT, 5-carboxamidotryptamine (5-CT, non-selective 5-HT1 agonist), and sumatriptan (5-HT1D-like receptor agonist) were studied. The effects of methiothepin (non-selective 5-HT1 + 2-receptor antagonist) and ketanserin (5-HT2A receptor antagonist) and GR55562 (a novel selective 5-HT1D receptor antagonist) on 5-HT-mediated responses were also studied. Basal levels of adenosine 3':5'-cyclic monophosphate ([cyclic AMP]i) and guanosine 3':5'-cyclic monophosphate ([cyclic GMP]i) were determined and we assessed the degree of inherent tone in the vessels under study. 2. 5-HT was most potent in the resistance arteries. pEC50 values were 5.6 +/- 0.1, 5.3 +/- 0.1, 5.0 +/- 0.2 in the resistance arteries, pulmonary branch and main pulmonary artery, respectively (n = at least 5 from 5 animals). The sensitivity to, and maximum response of, 5-HT was increased in all the arteries removed from the chronic hypoxic (CH) rats. In CH rats the pEC50 values were 5.9 +/- 0.2, 6.3 +/- 0.2, 6.4 +/- 0.2 and the increase in the maximum response was 35%, 51% and 41% in the resistance arteries, pulmonary branch and main pulmonary artery, respectively. Sumatriptan did not contract any vessel from the control rats whilst 5-CT did contract the resistance arteries. In the CH rats, however, they both contracted the resistance arteries (responses to sumatriptan were small) (pEC50: 5-CT; 5.4 +/- 0.2) and the pulmonary artery branches (pEC50: sumatriptan, 5.4 +/- 0.2; 5-CT, 5.4 +/- 0.2). 5-CT also caused a contraction in the main pulmonary artery (pEC50: 6.0 +/- 0.3). 3. Ketanserin (1 nM-1 microM) caused a competitive antagonism of the 5-HT response in all vessels tested. In control rats, the estimated pKb values for ketanserin in resistance arteries, pulmonary branches and main pulmonary

  10. [Cardiovascular risk factors in young adults with arterial hypertension and/or diabetes mellitus].

    PubMed

    Moreira, Thereza Maria Magalhães; Gomes, Emiliana Bezerra; dos Santos, Jênifa Cavalcante

    2010-12-01

    In this study we aimed to investigate the risk factors associated with arterial hypertension and diabetes mellitus in young adults assisted in six Family Health Units (UBASF), of Fortaleza, Ceará, Brazil. This is a descriptive and documental study, based on the records of the Care Program to Arterial Hypertension and Diabetes Mellitus (HIPERDIA). The sample was composed of 60 records, including hypertensive, diabetics and patients with the two diagnoses. The results showed prevalence of young female adults (78%). Regarding the risk factors, arterial hypertension (n=45), family history (n=33), overweight (n=33) and sedentary lifestyle (n=27) stood out. Regarding the cardiovascular risk stratification, most presented Medium additional risk for cardiovascular disease. We concluded that the individualized evaluation of risk factors supports an action addressed for possible events, being necessary investments in prevention and also in training and maintenance of the HIPERDIA system.

  11. 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.

  12. Complement C1q-induced activation of β-catenin signalling causes hypertensive arterial remodelling

    PubMed Central

    Sumida, Tomokazu; Naito, Atsuhiko T.; Nomura, Seitaro; Nakagawa, Akito; Higo, Tomoaki; Hashimoto, Akihito; Okada, Katsuki; Sakai, Taku; Ito, Masamichi; Yamaguchi, Toshihiro; Oka, Toru; Akazawa, Hiroshi; Lee, Jong-Kook; Minamino, Tohru; Offermanns, Stefan; Noda, Tetsuo; Botto, Marina; Kobayashi, Yoshio; Morita, Hiroyuki; Manabe, Ichiro; Nagai, Toshio; Shiojima, Ichiro; Komuro, Issei

    2015-01-01

    Hypertension induces structural remodelling of arteries, which leads to arteriosclerosis and end-organ damage. Hyperplasia of vascular smooth muscle cells (VSMCs) and infiltration of immune cells are the hallmark of hypertensive arterial remodelling. However, the precise molecular mechanisms of arterial remodelling remain elusive. We have recently reported that complement C1q activates β-catenin signalling independent of Wnts. Here, we show a critical role of complement C1-induced activation of β-catenin signalling in hypertensive arterial remodelling. Activation of β-catenin and proliferation of VSMCs were observed after blood-pressure elevation, which were prevented by genetic and chemical inhibition of β-catenin signalling. Macrophage depletion and C1qa gene deletion attenuated the hypertension-induced β-catenin signalling, proliferation of VSMCs and pathological arterial remodelling. Our findings unveil the link between complement C1 and arterial remodelling and suggest that C1-induced activation of β-catenin signalling becomes a novel therapeutic target to prevent arteriosclerosis in patients with hypertension. PMID:25716000

  13. 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.

  14. 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

  15. [Anesthetic Management for Non-cardiac Surgery in a Patient with Severe Pulmonary Arterial Hypertension].

    PubMed

    Ohno, Sho; Niiyama, Yukitoshi; Murouchi, Takeshi; Yamakage, Michiaki

    2016-05-01

    Severe pulmonary arterial hypertension is a significant risk factor for anesthetic management in patients undergoing even non-cardiac surgery. A 64-year-old female patient with severe pulmonary arterial hypertension was scheduled to undergo inguinal hernioplasty. Preoperative systolic pulmonary arterial pressure was 115 mmHg. We selected monitored anesthesia care with 0.2-0.5 μg x kg(-1) x hr(-1) dexmedetomidine and ultrasound-guided iliohypogastric block. Thereafter, LiDCOrapid was used to acquire the hemodynamic responses during surgery. Continuous iliohypogastric block produced postoperative pain relief and the supplemental analgesic was not needed. The monitored anesthesia care by dexmedetomidine and ultrasound guided continuous iliohypogastric block would be a safe procedure for patients with severe pulmonary arterial hypertension undergoing non-cardiac surgery. LiDCO rapid could be low invasive and useful as a hemodaynamic monitor in such a case. PMID:27319099

  16. [Metabolic syndrome with vascular risk and arterial hypertension].

    PubMed

    Wassermann, A O; Grosso, C P

    1996-01-01

    Hypertension is associated with metabolic disturbances that may be related to hyperinsulinemia, both resulting from our lifestyle. Insulin resistance generated by central obesity, and complex relations with sympathetic activity, dyslipemia, atherosclerosis, sodium retention, altered vascular reactivity and hypertension, lead to pathophysiological connections, that are still to be understood. Even if obesity and hypertension were not related through hyperinsulinemia, the metabolic syndrome increases either vascular risk or hypertension, and it has to be re-evaluated whether essential hypertension is an adequate diagnosis for these patients.

  17. [Metabolic syndrome with vascular risk and arterial hypertension].

    PubMed

    Wassermann, A O; Grosso, C P

    1996-01-01

    Hypertension is associated with metabolic disturbances that may be related to hyperinsulinemia, both resulting from our lifestyle. Insulin resistance generated by central obesity, and complex relations with sympathetic activity, dyslipemia, atherosclerosis, sodium retention, altered vascular reactivity and hypertension, lead to pathophysiological connections, that are still to be understood. Even if obesity and hypertension were not related through hyperinsulinemia, the metabolic syndrome increases either vascular risk or hypertension, and it has to be re-evaluated whether essential hypertension is an adequate diagnosis for these patients. PMID:8935572

  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. 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

  20. Clinical Implications of Hemoptysis in Patients with Pulmonary Arterial Hypertension

    PubMed Central

    Cantu, Jose; Wang, Degang; Safdar, Zeenat

    2013-01-01

    Introduction Pulmonary arterial hypertension (PAH) is a disabling disease that may result in haemoptysis. Patients with congenital heart disease associated PAH (CHD-APAH) may have a survival advantage when compared with patients with other types of PAH presenting with haemoptysis. The effects of aetiology and sub-sequent management choice of haemoptysis in PAH patients is not well-defined. Methods We conducted outcome analysis in CHD-APAH vs. all other subtypes of PAH patients presenting with haemoptysis to The Methodist Hospital. Twenty-one patients were identified, thirteen patients in the CHD-APAH group and eight patients in the non-CHD group. We evaluated outcomes related to treatment (bronchial artery embolization vs. conservative management), hospital length of stay, mortality rates and survival in this cohort. Results The CHD-APAH and non-CHD groups had similar baseline demographic, haemodynamic and laboratory values except BMI was higher in the non-CHD group and haematocrit was higher in the CHD-APAH group. Twenty-eight-day mortality (0% vs. 31%) and 1-year mortality (0% vs. 54%) was lower in the CHD-APAH patients as compared with non-CHD group. A statistically significant difference was found in the survival rate in favour of CHD-APAH group for the total follow-up period (p = 0.02). Although not statistically significant, patients treated with BAE had shorter length of stay (4.0 days ± 4.0 vs. 13.7 days ± 22.5; p = 0.26). There was recurrent haemoptysis in 43% of patients treated with BAE. Conclusion Haemoptysis in PAH patients is a serious event with a high mortality rate. CHD-APAH seems to confer a survival advantage, independent of therapy utilised. Termination of haemoptysis with BAE is rapid with relatively few complications except for frequent re-bleeding episodes. Further studies are needed to determine the risk factors that may predispose PAH patients to excessive mortality from haemoptysis and to identify an optimal therapeutic modality. PMID

  1. Novel biomarkers for risk stratification in pulmonary arterial hypertension

    PubMed Central

    Zelniker, Thomas; Uhlmann, Lorenz; Spaich, Sebastian; Friedrich, Jörg; Preusch, Michael R.; Meyer, Franz J.; Katus, Hugo A.

    2015-01-01

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

  2. The heart and pulmonary arterial hypertension in systemic sclerosis.

    PubMed

    Vandecasteele, Els H; De Pauw, Michel; Brusselle, Guy; Decuman, Saskia; Piette, Yves; De Keyser, Filip; Smith, V

    2016-02-01

    Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vasculopathy and progressive fibrosis of the skin and visceral organs (gastrointestinal tract, heart, kidneys and lungs). Although the prevalence is low, SSc is a disease with high morbidity and mortality. Since pulmonary arterial hypertension (PAH) associated with SSc (SSc-PAH) and clinically evident cardiac involvement is associated with increased mortality, the cardiac complications and PAH in SSc are reviewed. Both diffuse cutaneous (DcSSc) and limited cutaneous (LcSSc) subgroups are at risk for cardiac involvement and SSc-PAH. Cardiac involvement can be divided in pericardial involvement, myocardial involvement and rhythm disturbances and mostly occurs asymptomatically. However, when symptomatic, it is associated with a poor prognosis. Screening for asymptomatic cardiac involvement should be considered in SSc in order to initiate treatment in an early stage. However, there are no randomized controlled trials on treatment options for cardiac involvement in SSc. SSc-PAH is a devastating complication of SSc, which can develop early in DcSSc and LcSSc. Screening for PAH should be performed since screening leads to earlier diagnosis and earlier treatment is associated with a better prognosis. Today, screening is performed by clinical judgement and echocardiography. Recently the DETECT algorithm, a 2-step screening algorithm is proposed in a SSc-subgroup at increased risk for PAH, but further validation is needed. Despite current treatment options with prostacyclins, endothelin-1 receptor antagonists and phosphodiesterase type-5 inhibitors, mortality remains high. Several promising new treatment options for PAH are evaluated in phase II and III clinical trials. PMID:27075793

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

    PubMed Central

    Schilz, Robert; Mediratta, Anuj; Addetia, Karima; Coslet, Sandra; Thomeas, Vasiliki; Gillies, Hunter; Oudiz, Ronald J.

    2015-01-01

    Abstract Pulmonary arterial hypertension (PAH) causes right ventricular ischemia, dysfunction, and failure. PAH patients may benefit from antianginal agents based on a shared pathophysiology with left ventricular ischemia. A single-center, randomized, placebo-controlled trial (1∶1) to assess the acute vasoreactivity and safety of ranolazine in PAH was conducted. Plasma samples for pharmacokinetic (PK) studies were drawn during hemodynamic measurements at 0, 60, 90, 120, 240, and 360 minutes from a Swan-Ganz catheter. All patients received 500-mg doses, uptitrated to 1,000 mg at week 4, monthly evaluations, and a complete objective assessment after 12 weeks, followed by an open-label extension. Thirteen patients were randomized and 12 enrolled (6 ranolazine, 6 placebo). All patients completed the acute phase; 10 completed the 12-week study. There were no acute changes in invasive hemodynamics. At 12 weeks ranolazine was well tolerated. Only 1 of the 5 patients on ranolazine had a serum concentration considered to be in the therapeutic range. Two serious adverse events required early withdrawal (both in the ranolazine group); gastrointestinal complaints were the most common adverse event. Efficacy measures did not demonstrate any differences between treatment groups. During the open-label trial, 2 additional patients reached a therapeutic concentration. Ranolazine in PAH appears safe, without acute hemodynamic effects after a 500-mg dose. Ranolazine administrated to PAH patients receiving background PAH therapies did not consistently reach therapeutic levels. Future studies should first perform PK analysis in PAH patients receiving PAH therapies and explore the safety and tolerability of the higher doses perhaps necessary to achieve therapeutic levels in PAH patients. (Trial registration: Clinicaltrials.gov identifier NCT01757808.) PMID:26697176

  4. Bisoprolol in idiopathic pulmonary arterial hypertension: an explorative study.

    PubMed

    van Campen, Jasmijn S J A; de Boer, Karin; van de Veerdonk, Mariëlle C; van der Bruggen, Cathelijne E E; Allaart, Cor P; Raijmakers, Pieter G; Heymans, Martijn W; Marcus, J Tim; Harms, Hendrik J; Handoko, M Louis; de Man, Frances S; Vonk Noordegraaf, Anton; Bogaard, Harm-Jan

    2016-09-01

    While beta-blockers are considered contraindicated in pulmonary arterial hypertension (PAH), the prognostic significance of sympathetic nervous system over-activity suggests a potential benefit of beta-blocker therapy. The aim of this randomised, placebo-controlled, crossover, single centre study was to determine the effects of bisoprolol on right ventricular ejection fraction (RVEF) in idiopathic PAH (iPAH) patients. Additional efficacy and safety parameters were explored.Patients with optimally treated, stable iPAH (New York Heart Association functional class II/III) were randomised to placebo or bisoprolol. Imaging and functional measurements were performed at baseline, crossover and end of study.18 iPAH patients were included, because inclusion faltered before enrolment of the targeted 25 patients. 17 patients completed 6 months of bisoprolol, 15 tolerated bisoprolol, one patient required intravenous diuretics. Bisoprolol was associated with a lower heart rate (17 beats per minute, p=0.0001) but RVEF remained unchanged. A drop in cardiac index (0.5 L·min(-1)·m(-2), p=0.015) was observed, along with a trend towards a decreased 6-min walking distance (6MWD).Although careful up-titration of bisoprolol was tolerated by most patients and resulted in a decreased heart rate, no benefit of bisoprolol in iPAH was demonstrated. Decreases in cardiac index and 6MWD suggest a deteriorated cardiac function. The results do not favour the use of bisoprolol in iPAH patients. PMID:27390285

  5. Pulmonary arterial hypertension among Filipino patients with connective tissue diseases.

    PubMed

    Santos Estrella, Paul V; Lin, Yih Chang; Navarra, Sandra V

    2007-01-01

    We describe the clinical features, therapies, and clinical course of pulmonary arterial hypertension (PAH) in a group of Filipinos with connective tissue diseases (CTDs). We retrospectively reviewed the records of patients diagnosed with PAH by a two-dimensional echocardiogram as a tricuspid regurgitant jet of more than 25 mmHg. All patients had underlying CTDs, defined by the American College of Rheumatology criteria, and were seen at the rheumatology clinics of the University of Santo Tomas Hospital and the St. Luke's Medical Center, Philippines. Of the 33 patients (32 women) included in the analysis, there were 14 patients with systemic lupus erythematosus (SLE), 12 with scleroderma, 5 with mixed connective tissue disease (MCTD), 1 with primary antiphospholipid syndrome (APS), and 1 with dermatomyositis. The average age at PAH diagnosis was 38 +/- 14 years (mean +/- SD), and the mean duration of illness from CTD to PAH diagnosis was 53 +/- 52 months. Twelve patients had died at the time of this report, with a median duration of 15 months (range 1-57 months) from PAH diagnosis to mortality: six of these had scleroderma, five with SLE, and one with APS. The following therapies were used in this group of patients: low molecular weight heparin, warfarin, calcium-channel blockers, aspirin, cyclophosphamide, bosentan, iloprost, and sildenafil. We have described the clinical profile of PAH in a group of Filipino patients with CTDs, most commonly SLE. Various forms of pharmacologic therapies were used among these patients. Mortality remains high, particularly among those with underlying scleroderma. Early recognition and treatment are crucial in order to provide a better outcome for these patients.

  6. Noninvasive pulmonary artery wave intensity analysis in pulmonary hypertension.

    PubMed

    Quail, Michael A; Knight, Daniel S; Steeden, Jennifer A; Taelman, Liesbeth; Moledina, Shahin; Taylor, Andrew M; Segers, Patrick; Coghlan, Gerry J; Muthurangu, Vivek

    2015-06-15

    Pulmonary wave reflections are a potential hemodynamic biomarker for pulmonary hypertension (PH) and can be analyzed using wave intensity analysis (WIA). In this study we used pulmonary vessel area and flow obtained using cardiac magnetic resonance (CMR) to implement WIA noninvasively. We hypothesized that this method could detect differences in reflections in PH patients compared with healthy controls and could also differentiate certain PH subtypes. Twenty patients with PH (35% CTEPH and 75% female) and 10 healthy controls (60% female) were recruited. Right and left pulmonary artery (LPA and RPA) flow and area curves were acquired using self-gated golden-angle, spiral, phase-contrast CMR with a 10.5-ms temporal resolution. These data were used to perform WIA on patients and controls. The presence of a proximal clot in CTEPH patients was determined from contemporaneous computed tomography/angiographic data. A backwards-traveling compression wave (BCW) was present in both LPA and RPA of all PH patients but was absent in all controls (P = 6e(-8)). The area under the BCW was associated with a sensitivity of 100% [95% confidence interval (CI) 63-100%] and specificity of 91% (95% CI 75-98%) for the presence of a clot in the proximal PAs of patients with CTEPH. In conclusion, WIA metrics were significantly different between patients and controls; in particular, the presence of an early BCW was specifically associated with PH. The magnitude of the area under the BCW showed discriminatory capacity for the presence of proximal PA clot in patients with CTEPH. We believe that these results demonstrate that WIA could be used in the noninvasive assessment of PH. PMID:25659483

  7. 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

  8. Predictors and outcomes of resistant hypertension among patients with coronary artery disease and hypertension

    PubMed Central

    Smith, Steven M.; Gong, Yan; Handberg, Eileen; Messerli, Franz H.; Bakris, George L.; Ahmed, Ali; Bavry, Anthony A.; Pepine, Carl J.; Cooper-DeHoff, Rhonda M.

    2014-01-01

    Objective Resistant hypertension (res-HTN) is a challenging problem, but little is known of res-HTN in patients with coronary artery disease (CAD). In this post-hoc INternational VErapamil SR-Trandolapril STudy (INVEST) analysis, we assessed prevalence, predictors, and impact on outcomes of res-HTN in CAD patients with hypertension. Methods Participants (n=17 190) were divided into three groups according to achieved blood pressure (BP): controlled (BP <140/90 mmHg on three or fewer drugs); uncontrolled (BP ≥140/90mmHg on two or fewer drugs); or resistant (BP ≥140/90 mmHg on three drugs or any patient on at least four drugs). Results The prevalence of res-HTN was 38%: significant predictors of res-HTN included heart failure [odds ratio (OR) 1.73], diabetes (OR 1.63), Black race (OR 1.50), and US residence (OR 1.50). Compared with controlled HTN, res-HTN had multivariate-adjusted association with higher risk of adverse outcomes {first occurrence of all-cause death, nonfatal myocardial infarction, or nonfatal stroke [hazard ratio 1.27, 95% confidence interval (CI) 1.13–1.43], and individual outcomes of all-cause death (hazard ratio 1.29, 95% CI 1.13–1.48), cardiovascular mortality (hazard ratio 1.47, 95% CI 1.21–1.78), and nonfatal stroke (hazard ratio 1.61, 95% CI 1.17–2.22), but not nonfatal myocardial infarction (hazard ratio 0.98, 95% CI 0.72–1.34)}. Adverse outcomes, except nonfatal stroke, did not differ in patients with res-HTN compared to uncontrolled HTN. Conclusions Res-HTN is common in patients with CAD and hypertension, associated with poor prognosis, and linked with a number of conditions. Emphasis should be placed on recognizing those at risk for res-HTN and future studies should examine whether more aggressive treatment of res-HTN improves outcomes. PMID:24299915

  9. 17β-Estradiol Attenuates Conduit Pulmonary Artery Mechanical Property Changes With Pulmonary Arterial Hypertension.

    PubMed

    Liu, Aiping; Tian, Lian; Golob, Mark; Eickhoff, Jens C; Boston, Madison; Chesler, Naomi C

    2015-11-01

    Pulmonary arterial hypertension (PAH), a rapidly fatal vascular disease, strikes women more often than men. Paradoxically, female PAH patients have better prognosis and survival rates than males. The female sex hormone 17β-estradiol has been linked to the better outcome of PAH in females; however, the mechanisms by which 17β-estradiol alters PAH progression and outcomes remain unclear. Because proximal pulmonary arterial (PA) stiffness, one hallmark of PAH, is a powerful predictor of mortality and morbidity, we hypothesized that 17β-estradiol attenuates PAH-induced changes in mechanical properties in conduit proximal PAs, which imparts hemodynamic and energetic benefits to right ventricular function. To test this hypothesis, female mice were ovariectomized and treated with 17β-estradiol or placebo. PAH was induced in mice using SU5416 and chronic hypoxia. Extra-lobar left PAs were isolated and mechanically tested ex vivo to study both static and frequency-dependent mechanical behaviors in the presence or absence of smooth muscle cell activation. Our static mechanical test showed significant stiffening of large PAs with PAH (P<0.05). 17β-Estradiol restored PA compliance to control levels. The dynamic mechanical test demonstrated that 17β-estradiol protected the arterial wall from the PAH-induced frequency-dependent decline in dynamic stiffness and loss of viscosity with PAH (P<0.05). As demonstrated by the in vivo measurement of PA hemodynamics via right ventricular catheterization, modulation by 17β-estradiol of mechanical proximal PAs reduced pulsatile loading, which contributed to improved ventricular-vascular coupling. This study provides a mechanical mechanism for delayed disease progression and better outcome in female PAH patients and underscores the therapeutic potential of 17β-estradiol in PAH. PMID:26418020

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

    PubMed

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

    2016-03-01

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

  11. Genistein treatment reduces arterial contractions by inhibiting tyrosine kinases in ovariectomized hypertensive rats.

    PubMed

    Nevala, Riikka; Lassila, Markus; Finckenberg, Piet; Paukku, Kirsi; Korpela, Riitta; Vapaatalo, Heikki

    2002-09-27

    The aim of the present study was to evaluate the vascular effects of genistein in a short-term study. The ovariectomized spontaneously hypertensive rats (SHR) were divided into four groups (n = 8 in each), which received the following subcutaneous treatments either for 2 days or for 2 weeks: (1) solvent control (96% dimethylsulphoxide (DMSO) 1 ml/kg), (2) estradiol-17beta (25 microg/kg), (3) genistein (2.5 mg/kg; low-dose), and (4) genistein (25 mg/kg; high-dose). The renal arterial rings were studied using organ bath system. The renal artery contractions were attenuated by the 2-day low-dose genistein treatment as follows: angiotensin II (46%), noradrenaline (42%) KCl (36%), and endothelin-1 (34%). Only the angiotensin II-induced contractions were reduced by the 2-week treatment with estradiol-17beta (38%) and with the low-dose of genistein (31%). The 2-day genistein treatment reduced tyrosine phosphorylation, while the other treatments or treatment times had no effect. The 2-day low-dose genistein treatment had no estrogenic effect on the uterine morphology. The mechanism for attenuated contractility in the renal arteries after the 2-day low-dose genistein treatment is independent of the estrogenic effect of genistein, but is due to the tyrosine kinase inhibitory property of genistein.

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

    PubMed Central

    Lee, Jae Chul; Kim, Kwan Chang

    2016-01-01

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

  13. Diagnostic and therapeutic strategies for resistant arterial hypertension--focus on countries with emerging economies.

    PubMed

    Zhanatbekova, A K; Karazhanova, L K; Begalina, A M; Filipova, S

    2014-01-01

    Arterial hypertensionis an important worldwide health problem. Its relevance relates both to the high incidence and prevalence in all adult communities and to the high risk of serious and potentially fatal cardiovascular events due to hypertension. Resistant hypertension is defined as a blood pressure (BP) remaining above goal (>140/90 mm Hg) despite the use of at least 3 optimally dosed antihypertensive drugs from different classes, with one of the drugs being a diuretic. The exact prevalence of RH is unknown, but it is generally estimated at 10-20% of hypertensive patients. The aim of this review article is to address several important issues: (1) How to diagnose true RH ? (2) What is the optimal state-of-art management of RH in the light of the most recent scientific evidence and what is the role of various medical specialties in this process ? (3) Are there any country specific issues related to diagnosing and treating of RH in Kazakhstan and if so, how to tackle them ?Long-lasting resistant hypertension increases by 50-80% the risk of major cardiovascular events (myocardial infarction, stroke) and end-organ damage. (heart failure, vascular dementia, chronic kidney disease). Adherence to well chosen therapy is the key factor in achieving blood pressure control and this must be based on adequate patient education and universal access to drug therapy. Thus, early recognition and appropriate management of RH must be among the top priorities of all public health initiatives to reduce the burden of cardiovascular diseases (Tab. 2, Fig. 1, Ref. 31).

  14. Macular circulation in patients with diabetes mellitus with and without arterial hypertension

    PubMed Central

    Arend, O; Ruffer, M; Remky, A

    2000-01-01

    BACKGROUND—Previous fluorescein angiographic studies have shown alterations in the macular microcirculation in patients with diabetes mellitus and arterial hypertension. In both diseases capillary blood velocity was reduced and capillary density decreased. These changes were more pronounced in diabetic patients. We have examined the influence of arterial hypertension in combination with diabetes mellitus.
METHODS—62 patients with diabetes mellitus and arterial hypertension (group 1) were matched with patients with diabetes mellitus but without arterial hypertension (group 2, match criteria: ETDRS stage of retinopathy). In all subjects fluorescein angiograms were performed with a scanning laser ophthalmoscope. Macular capillary blood velocity (CBV), perifoveal intercapillary area (PIA), the coefficient of variation of both parameters, the area of the foveal avascular zone (FAZ), and the arteriovenous passage time (AVP) were assessed by digital image analysis.
RESULTS—Systolic and diastolic blood pressures were significantly increased in the patients with arterial hypertension (systolic p=0.0008; diastolic p=0.03). Neither dynamic measures (AVP: 1.64 (0.49) seconds (group 1), 1.72 (0.58) seconds (group 2); CBV: 1.98 (0.39) mm/s (group 1), 2.09 (0.43) mm/s (group 2)) nor morphological measures (PIA: 7985 (3137) µm2 (group 1), 8338 (3376) µm2 (group 2); FAZ: 0.319 (0.206) mm2 (group 1), 0.363 (0.237) mm2 (group 2)) were significantly different between the two groups of diabetic patients.
CONCLUSION—Arterial hypertension did not result in more severe macular capillary dropout than diabetes without hypertension. This might be explained by the fact that most of the patients were being treated with antihypertensive drugs.

 PMID:11090480

  15. Arterial wall metabolism in experimental hypertension of coarctation of the aorta of short duration

    PubMed Central

    Hollander, William; Kramsch, Dieter M.; Farmelant, Melvin; Madoff, Irving M.

    1968-01-01

    Coarctation of the mid-thoracic aorata was surgically produced in mongrel dogs which were sacrificed from 4-12 wk after the operation. As compared to the findings in control animals, the sodium, chloride, and water content of the hypetensive portion of the coarcted thoracic aorta was significantly elevated, whereas the electrolyte and water content of the relatively normotensive portion of the coarcted aorta was normal. The sodium, potassium, and water content of the pulmonary artery, skeletal muscle, and cardiac muscle of the coarcted dog was not altered. These observations suggest that an elevated arterial pressure may influence the electrolyte and water composition of the arteries. The arterial pressure also may influence the content and synthesis of acid mucopolysaccharides (MPS) in the arteries since the content of sulfated MPS and the incorporation of injected radiosulfate into sulfated MPS were significantly increased in the hypertensive portion of the coarcted thoracic aorta but were significantly reduced in the relatively normotensive (“hypotensive”) portion of the coarcted aorta. The observed increase in MPS may have been a factor directly responsible for the increase in the sodium content of the hypertensive aorta since MPS can act as polyelectrolytes and bind cations. Although the arterial pressure may influence certain metabolic functions in the arteries, it did not appear to have a direct effect on the arterial lipids since the lipid content of the hypertensive and of the relatively normotensive portions of the coarcted aorta were comparable to the values found in the normal aorta. Images PMID:5645864

  16. Stiffening of the Extrapulmonary Arteries From Rats in Chronic Hypoxic Pulmonary Hypertension.

    PubMed

    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

  17. Pulmonary vascular disease in mice xenografted with human BM progenitors from patients with pulmonary arterial hypertension

    PubMed Central

    Farha, Samar; Lichtin, Alan; Graham, Brian; George, Deepa; Aldred, Micheala; Hazen, Stanley L.; Loyd, James; Tuder, Rubin

    2012-01-01

    Hematopoietic myeloid progenitors released into the circulation are able to promote vascular remodeling through endothelium activation and injury. Endothelial injury is central to the development of pulmonary arterial hypertension (PAH), a proliferative vasculopathy of the pulmonary circulation, but the origin of vascular injury is unknown. In the present study, mice transplanted with BM-derived CD133+ progenitor cells from patients with PAH, but not from healthy controls, exhibited morbidity and/or death due to features of PAH: in situ thrombi and endothelial injury, angioproliferative remodeling, and right ventricular hypertrophy and failure. Myeloid progenitors from patients with heritable and/or idiopathic PAH all produced disease in xenografted mice. Analyses of hematopoietic transcription factors and colony formation revealed underlying abnormalities of progenitors that skewed differentiation toward the myeloid-erythroid lineage. The results of the present study suggest a causal role for hematopoietic stem cell abnormalities in vascular injury, right ventricular hypertrophy, and morbidity associated with PAH. PMID:22745307

  18. 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.

  19. 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

  20. Pathways and Drugs in Pulmonary Arterial Hypertension - Focus on the Role of Endothelin Receptor Antagonists.

    PubMed

    Madonna, Rosalinda; Cocco, Nino; De Caterina, Raffaele

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a group of diseases characterized by a progressive increase of pulmonary vascular resistance (PVR), initially due to abnormal pulmonary vasoconstriction in response to endothelial injury. Recent studies have here confirmed the prominent role of endothelin (ET)-1 in vasoconstriction and remodelling of the pulmonary microcirculation. In patients who are acute-vasoreactive, classical treatments for PAH are calcium channels blockers (CCBs), while drugs targeting the prostacyclin, nitric oxide and endothelin pathways, i.e., prostanoids, phosphodiesterase (PDE)-5 inhibitors and endothelin receptor antagonists (ERAs), respectively, are indicated in non-vasoreactive patients or in vasoreactive patients not responding to initial CCB therapy. Randomised, placebo-controlled trials have shown that ERAs improve pulmonary haemodynamics, exercise capacity, functional status and clinical outcome in patients with PAH. Here we provide an overview of the currently recommended diagnostic and therapeutic work-up in PAH, with special emphasis on ERAs. PMID:26145170

  1. 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

  2. Laparoscopic nephrectomy for complete renal infarction due to post traumatic renal artery thrombosis.

    PubMed

    Gidaro, Stefano; Schips, Luigi; Cindolo, Luca; Ziguener, Richard

    2008-06-01

    We report a case of post traumatic thrombosis of the renal artery with renal infarction and associated liver injury. Conservative treatment was initially planned in consideration of the delayed diagnosis (> 3 hours), but the patient subsequently developed hypertension not controllable with anti-hypertensive drugs. He underwent laparoscopy with nephrectomy and liver injury repair. Hypertension resolved after nephrectomy without further medical treatment. Laparoscopic nephrectomy is not a standard procedure for renal trauma but it could be an option in selected patients.

  3. [The effect of different factors on cardiac rhythm variability in patients with arterial hypertension].

    PubMed

    Riabykina, G V; Sobolev, A V; Pushina, E A; Liutikova, L N; Sergakova, L M; Aleeva, M A; Ustinova, S E; Arabidze, G G

    1997-01-01

    The purpose of this study was to evaluate the influence of different factors, among them left ventricular hypertrophy (LVH) on long-term heart rate variability (HRV) in patients with hypertension. 38 patients with arterial hypertension of different genesis were included in the study. Ischemia was excluded in all the patients by the data of clinical and instrumental methods of investigation. LVH data obtained from HRV of 20 healthy subjects was used as control. HRV was evaluated by estimating variations for short intervals of a rhythmogram (VSI). A HRV decrease did not depend on sex, but essentially depended on patients'a age, disease duration and the form of hypertension. A marked tendency leading to the rate variability decrease was observed only in moderate LVH. In cases of original LVH variability data did not differ from those in patients without signs of LVH. Low or marginal HRV was more often observed in patients with essential hypertension and in those with hypertension of endocrine genesis. As far as renal hypertension is concerned low variability was less frequent. There were a lot of factors which affect the change of HRV. The more significant of them were the patients' age, hypertension genesis and form of hypertension. Factors leading to the rate variability decrease were the following age above 40, endocrine or essential hypertension and moderate form of hypertension.

  4. Prevalence of pseudoresistant hypertension due to inaccurate blood pressure measurement.

    PubMed

    Bhatt, Hemal; Siddiqui, Mohammed; Judd, Eric; Oparil, Suzanne; Calhoun, David

    2016-06-01

    The prevalence of pseudoresistant hypertension (HTN) due to inaccurate BP measurement remains unknown. 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 (VSM Med Tech Ltd. Coquitlam, Canada) device. The prevalence of uncontrolled RHTN and differences in BP measurements were compared. Of 130 patients with uncontrolled RHTN, 33.1% (n = 43) were falsely identified as having uncontrolled RHTN based on triage BP measurements. The median (inter-quartile range) 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 = .0001). The median (inter-quartile range) of differences in diastolic BP between the two groups were 12 (7-18) mm Hg and 8 (4-11) mm Hg, respectively (P = .001). 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

  5. Structural and functional analysis of small arteries from young spontaneously hypertensive rats.

    PubMed

    Dickhout, J G; Lee, R M

    1997-03-01

    We studied structural and functional changes of small muscular arteries from the mesenteric vascular bed of young spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) using a new morphometric protocol involving the use of confocal microscopy and a pressurized artery system. At 3 and 4 weeks of age, systolic pressure of SHR and WKY was similar; however, significant structural changes in the mesenteric vasculature were already present in SHR. Arteries fixed under pressure in vitro from SHR had a larger medial volume and increased number of smooth muscle cell layers but similar lumen size compared with arteries from WKY in maximally relaxed conditions. Functional studies showed that SHR arteries contracted more in response to stimulation by KCl and norepinephrine, resulting in a significantly smaller lumen size in these vessels than in those from WKY. SHR arteries precontracted with KCl were also able to maintain a smaller lumen diameter than WKY arteries when challenged with increasing pressure levels. No difference in the sensitivity of response of these arteries to norepinephrine stimulation was found. At 3 and 4 weeks of age, mesenteric arteries from some SHR and WKY were not responsive to periarterial nerve stimulation, and the number of responders was higher in the WKY than SHR. However, a greater degree of contraction was found in SHR arteries responding to field stimulation at 4 weeks than in WKY arteries. We conclude that there is a temporal difference in the rate of functional maturation of the innervation in SHR arteries compared with WKY arteries. Structural changes of the small muscular arteries, caused by an increase in the medial volume, and increased number of smooth muscle cell layers are primary changes that contribute to the development of hypertension in the SHR because these changes are present at the age when blood pressure is similar in SHR and WKY.

  6. AMBITION: An important piece in the therapeutic puzzle of pulmonary arterial hypertension

    PubMed Central

    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. PMID:26779523

  7. Hypertension, obesity, and coronary artery disease in the survivors of congenital heart disease.

    PubMed

    Roche, S Lucy; Silversides, Candice K

    2013-07-01

    Obesity, hypertension, and coronary artery disease are prevalent in the general population and well recognized as contributors to cardiac morbidity and mortality. With surgical and medical advances, there is a growing and aging population with congenital heart disease who are also at risk of developing these comorbidities. In addition, some congenital cardiac lesions predispose patients to conditions such as hypertension or coronary artery disease. The effect of these comorbidities on the structurally abnormal heart is not well understood, but might be very important, especially in those with residual abnormalities. Thus, in addition to surveillance for and treatment of late complications it is important for the congenital cardiologist to consider and aggressively manage acquired comorbidities. In this review we explore the prevalence of hypertension, obesity, and coronary artery disease, discuss congenital lesions that predispose to these conditions and review management strategies for this unique population.

  8. Supraventricular Arrhythmias in Patients With Pulmonary Arterial Hypertension.

    PubMed

    Cannillo, Margherita; Grosso Marra, Walter; Gili, Sebastiano; D'Ascenzo, Fabrizio; Morello, Mara; Mercante, Lorena; Mistretta, Elisa; Salera, Davide; Zema, Domenica; Bissolino, Arianna; Fusaro, Enrico; Marra, Sebastiano; Libertucci, Daniela; Gaita, Fiorenzo

    2015-12-15

    The onset of supraventricular arrhythmias (SVA) may be associated with clinical worsening in patients with pulmonary arterial hypertension (PAH). However, limited data have been reported, especially at long-term follow-up. Aim of this study was to investigate the incidence of SVA in our patients with PAH, the risk factors correlated to their onset and the prognostic impact. All consecutive patients with PAH without history of SVA were enrolled. Incidence of new SVA was investigated and also the risk factors for SVA. Primary end point of the study was the impact of SVA on a composite of all-cause mortality and re-hospitalization, whereas mortality was the secondary end point. Seventy-seven patients were enrolled. No significant differences in the clinical or instrumental baseline characteristics between the 2 study groups were reported. During a median follow-up of 35 months (interquartile range 21.5 to 53.5), 17 (22%) patients experienced SVA. Development of SVA was associated with worsening of prognostic parameters at the follow-up: increasing of World Health Organization (WHO) functional class (p = 0.005) and N-terminal-pro-brain natriuretic peptide (NT-proBNP) (p = 0.018) and reduction of 6-minute walking distance (p = 0.048), tricuspid annular plane systolic excursion (TAPSE) (p = 0.041), and diffusing capacity of the lung for carbon monoxide (p = 0.025). The primary end point occurred in 13 patients (76%) in the SVA group and in 22 patients (37%) in the group without SVA (p = 0.004), whereas 9 patients (53%) among those with SVA died during the follow-up compared with 8 (13%) among those without (p = 0.001). At multivariate analysis, development of SVA was independently associated with an increased risk to meet the both primary (hazard ratio 2.13; 95% confidence interval 1.07 to 4.34; p = 0.031) and secondary (hazard ratio 4.1; 95% confidence interval 1.6 to 10.6; p = 0.004) end points. In conclusion, during the 3-year follow-up period, 1/3 of patients with

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

    PubMed

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

    1990-12-01

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

  10. [Possibilities of pharmacological correction of the arterial hypertension in elderly patients with gout].

    PubMed

    Kunitskaia, N A; Andrianova, M A

    2012-01-01

    The aim of this work was a detailed study of questions connected with the peculiarities of circadian blood pressure profile, efficiency of amlodipine in elderly patients with gout and arterial hypertension. We used 24-hour blood pressure monitoring before and after 3 and 6-months treatment. Patients with gout showed the disturbances of circadian blood pressure profile. Prolonged calcium antagonists are the best drugs for the hypertensive patients with gout.

  11. 17β-estradiol attenuates conduit pulmonary artery mechanical property changes with pulmonary arterial hypertension

    PubMed Central

    Liu, Aiping; Tian, Lian; Golob, Mark; Eickhoff, Jens C.; Boston, Madison; Chesler, Naomi C.

    2015-01-01

    Pulmonary arterial hypertension (PAH), a rapidly fatal vascular disease, strikes women more often than men. Paradoxically, female PAH patients have better prognosis and survival rates than males. The female sex hormone 17β-estradiol has been linked to the better outcome of PAH in females; however, the mechanisms by which 17β-estradiol alters PAH progression and outcomes remain unclear. Since proximal PA stiffness, one hallmark of PAH, is a powerful predictor of mortality and morbidity, we hypothesized that 17β-estradiol attenuates PAH-induced changes in mechanical properties in conduit proximal PAs, which imparts hemodynamic and energetic benefits to RV function. To test this hypothesis, female mice were ovariectomized and treated with 17β-estradiol or placebo. PAH was induced in mice using SU5416 and chronic hypoxia (SuHx). Extra-lobar left PAs were isolated and mechanically tested ex vivo to study both static and frequency-dependent mechanical behaviors in the presence or absence of SMC activation. Our static mechanical test showed significant stiffening of large PAs with PAH (P < 0.05). 17β-estradiol restored PA compliance to control levels. The dynamic mechanical test demonstrated that 17β-estradiol protected the arterial wall from the PAH-induced frequency-dependent decline in dynamic stiffness and loss of viscosity with PAH (P<0.05). As demonstrated by the in vivo measurement of PA hemodynamics via RV catheterization, modulation by 17β-estradiol of mechanical proximal PAs reduced pulsatile loading, which contributed to improved ventricular-vascular coupling. This study provides a mechanical mechanism for delayed disease progression and better outcome in female PAH patients and underscores the therapeutic potential of 17β-estradiol in PAH. PMID:26418020

  12. [The evaluation of medicinal therapy under treatment of arterial hypertension in hospital].

    PubMed

    Maksimova, T M; Lushkina, N P; Alekseeva, N Yu; Lomakina, E A; Saurina, O S; Telnova, E A

    2015-01-01

    The article presents the analysis of data of "Study on Global AGEing and Adult Health, 2007-2010" (SAGE) concerning subjective judging of health, prevalence of ischemic heart disease under different levels of arterial pressure in similar age groups. An attempt is made to evaluate spectrum of pharmaceuticals applied in treatment of patients with arterial pressure in hospital at the level of oblast hospital. According official statistics of Minzdrav of Russia, in 20102 prevalence of diseases characterized by higher arterial pressure amounted to 10.5% in adult population and to 22.3% in population older than able-bodied age. At the same time, according SAGE data, prevalence of various forms of hypertension disease in population older than 50 years amounted to 52.8%. That is, this pathology is often missed in conditions of mass medical network. Thereafter, patients receive no necessary medicinal therapy. The one or another treatment was provided to almost 94% of patients with hypertension disease diagnosed by physician. At that, among patients received treatment the normal levels of both systolic and diastolic pressure were established in less than 20% of patients with hypertension. Therefore, the issue of effectiveness of applied methods of correction of arterial hypertension become a matter of interest. The appropriate treatment of hypertension is a mean to decrease complications and as a result to diminish mortality of diseases of circulatory system.

  13. Transforming growth factor-beta 1 is decreased in remodeling hypertensive bovine pulmonary arteries.

    PubMed Central

    Botney, M D; Parks, W C; Crouch, E C; Stenmark, K; Mecham, R P

    1992-01-01

    The development of pulmonary hypertension in hypoxic newborn calves is associated with a complex pattern of increased tropoelastin and type I procollagen synthesis and deposition by smooth muscle cells in large elastic pulmonary arteries compared to normoxic controls. We examined the possibility that transforming growth factor-beta 1 (TGF-beta 1) may be associated with the production of extracellular matrix protein in this model of pulmonary hypertension. Medial smooth muscle cells in both normotensive and hypertensive vessels, as assessed by immunohistochemistry, were the major source of TGF-beta 1. Staining was confined to foci of smooth muscle cells in the outer media and appeared greater in normotensive than hypertensive vessels. Consistent with the immunohistochemistry, a progressive, age-dependent increase in normotensive pulmonary artery TGF-beta 1 mRNA was observed after birth, whereas TGF-beta 1 mRNA remained at low, basal levels in hypertensive, remodeling pulmonary arteries. These observations suggest that local expression of TGF-beta 1 is not associated with increased extracellular matrix protein synthesis in this model of hypoxic pulmonary hypertension. Images PMID:1569202

  14. Diagnosis and Treatment of Pulmonary Arterial Hypertension and Atrial Fibrillation in an Adult Chimpanzee (Pan troglodytes)

    PubMed Central

    Lammey, Michael L; Doane, Cynthia J; Gigliotti, Andrew; Lee, D Rick; Sleeper, Meg M

    2008-01-01

    This report describes the diagnosis and treatment of pulmonary arterial hypertension (PAH) in an adult male captive chimpanzee. Although cardiovascular disease in general is common in human and great apes, diagnosis and treatment of PAH in nonhuman primates are uncommon. In the case we present, the adult chimpanzee was diagnosed with an arrhythmia during an annual physical examination and later with PAH during a scheduled cardiovascular evaluation. PAH can either be primary or secondary and can lead to right ventricular overload and heart failure. This description is the first case study of pulmonary arterial hypertension in a great ape species. PMID:18947173

  15. [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).

  16. Role of Elastin in Spontaneously Hypertensive Rat Small Mesenteric Artery Remodelling

    PubMed Central

    Briones, Ana M; González, José M; Somoza, Beatriz; Giraldo, Jesús; Daly, Craig J; Vila, Elisabet; Carmen González, M; McGrath, John C; Arribas, Silvia M

    2003-01-01

    Chronic hypertension is associated with resistance artery remodelling and mechanical alterations. However, the contribution of elastin has not been thoroughly studied. Our objective was to evaluate the role of elastin in vascular remodelling of mesenteric resistance arteries (MRA) from spontaneously hypertensive rats (SHR). MRA segments from Wistar Kyoto rats (WKY) and SHR were pressurised under passive conditions at a range of physiological pressures with pressure myography. Confocal microscopy was used to determine differences in the quantity and organisation of elastin in intact pressure-fixed arteries. To assess the contribution of elastin to MRA structure and mechanics, myograph-mounted vessels were studied before and after elastase incubation. When compared with WKY, MRA from SHR showed: (1) a smaller lumen, (2) decreased distensibility at low pressures, (3) a leftward shift of the stress-strain relationship, (4) redistribution of elastin within the internal elastic lamina (IEL) leading to smaller fenestrae but no change in fenestrae number or elastin amount. Elastase incubation (1) fragmented the structure of IEL in a concentration-dependent fashion, (2) abolished all the structural and mechanical differences between strains, and (3) decreased distensibility at low pressures. The study shows the overriding role of elastin in determining vascular dimensions and mechanical properties in a resistance artery. In addition, it informs hypertensive remodelling. MRA remodelling and increased stiffness are accompanied by elastin restructuring within the IEL and elastin degradation reverses structural and mechanical alterations of SHR MRA. Differences in elastin organisation are, therefore, a central element in small artery remodelling in hypertension. PMID:12844513

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

    PubMed

    Bontemps, S; Pechère-Bertschi, A

    2015-09-01

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

  18. 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.

  19. 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.

  20. Development of pulmonary arterial hypertension during oral dasatinib therapy for chronic myelogenous leukemia.

    PubMed

    Morishita, Sakura; Hagihara, Maki; Itabashi, Megumi; Ishii, Yoshimi; Yamamoto, Wataru; Numata, Ayumi; Motohashi, Kenji; Matsumoto, Kenji; Fujisawa, Shin; Nakajima, Hideaki

    2016-08-01

    We present a 36-year-old woman who had been taking oral dasatinib for 3 years for the treatment of chronic myelogenous leukemia (CML). Although adverse events such as thrombocytopenia and pleural effusion developed, she showed a major molecular response (MMR) 22 months after the initiation of oral dasatinib administration, and the therapy was thus continued. Approximately 34 months after oral dasatinib initiation, she developed severe exertional dyspnea and had to be urgently hospitalized. There was no apparent pleural effusion increase, and neither imaging nor blood test results suggested pneumonia or other infections. Pulmonary arterial hypertension (PAH) was suspected on the basis of transthoracic echocardiography. PAH was then confirmed by right heart catheterization. Though dasatinib was discontinued on the day of hospitalization, pulmonary hypertension and heart failure progressed, and she did not respond to catecholamines or PDE5 (phosphodiesterase type 5) inhibitors. On the 4(th) hospital day, she experienced cardiopulmonary arrest and died 1 week later. Cases with PAH due to oral administration of dasatinib have been reported previously. However, cases showing the rapid progression documented in our patient are rare and we advocate that PAH be considered a potential adverse event associated with dasatinib therapy. PMID:27599415

  1. Potent vasoconstrictor actions of cyclopiazonic acid and thapsigargin on femoral arteries from spontaneously hypertensive rats

    PubMed Central

    Nomura, Yukiko; Asano, Masahisa; Ito, Katsuaki; Uyama, Yoshiaki; Imaizumi, Yuji; Watanabe, Minoru

    1996-01-01

    The Ca2+ buffering function of sarcoplasmic reticulum (SR) in the resting state of arteries from spontaneously hypertensive rats (SHR) was examined. Differences in the effects of cyclopiazonic acid (CPA) and thapsigargin, agents which inhibit the Ca2+-ATPase of SR, on tension and cellular Ca2+ level were assessed in endothelium-denuded strips of femoral arteries from 13-week-old SHR and normotensive Wistar-Kyoto rats (WKY).In resting strips preloaded with fura-PE3, the addition of CPA (10 μM) or thapsigargin (100 nM) caused an elevation of cytosolic Ca2+ level ([Ca2+]i) and a contraction. These responses were significantly greater in SHR than in WKY.The addition of verapamil (3 μM) to the resting strips caused a decrease in resting [Ca2+]i, which was significantly greater in SHR than in WKY. In SHR, but not in WKY, this decrease was accompanied by a relaxation from the resting tone, suggesting the maintenance of myogenic tone in the SHR artery.Verapamil (3 μM) abolished differences between SHR and WKY. The effects of verapamil were much greater on the contraction than on the [Ca2+]i.The resting Ca2+ influx in arteries measured after a 5 min incubation of the artery with 45Ca was not increased by CPA or thapsigargin in either SHR or WKY. The net Ca2+ entry measured after a 30 min incubation of the artery with 45Ca was decreased by CPA or thapsigargin in both SHR and WKY. The resting Ca2+ influx was significantly higher in SHR than in WKY, and was decreased by nifedipine (100 nM) in the SHR artery, but was unchanged in the WKY artery.The resting 45Ca efflux from the artery was increased during the addition of CPA (10 μM). This increase was less in SHR than in WKY. The resting 45Ca efflux was the same in SHR and WKY.These results suggest that (1) the Ca2+ influx via L-type voltage-dependent Ca2+ channels (VDCCs) was increased in the resting state of the SHR femoral artery, (2) the greater part of the increased Ca2+ influx was buffered by Ca2

  2. Endothelial dysfunction in experimental models of arterial hypertension: cause or consequence?

    PubMed

    Bernatova, Iveta

    2014-01-01

    Hypertension is a risk factor for other cardiovascular diseases and endothelial dysfunction was found in humans as well as in various commonly employed animal experimental models of arterial hypertension. Data from the literature indicate that, in general, endothelial dysfunction would not be the cause of experimental hypertension and may rather be secondary, that is, resulting from high blood pressure (BP). The initial mechanism of endothelial dysfunction itself may be associated with a lack of endothelium-derived relaxing factors (mainly nitric oxide) and/or accentuation of various endothelium-derived constricting factors. The involvement and role of endothelium-derived factors in the development of endothelial dysfunction in individual experimental models of hypertension may vary, depending on the triggering stimulus, strain, age, and vascular bed investigated. This brief review was focused on the participation of endothelial dysfunction, individual endothelium-derived factors, and their mechanisms of action in the development of high BP in the most frequently used rodent experimental models of arterial hypertension, including nitric oxide deficient models, spontaneous (pre)hypertension, stress-induced hypertension, and selected pharmacological and diet-induced models.

  3. The importance of the relationship between microalbuminuria, subclinical proteinuria and arterial hypertension in diabetics.

    PubMed

    Serban, V; Dabelea, D

    1994-01-01

    Arterial hypertension represents, among others, an important risk factor for the development of microalbuminuria in diabetics. On the other hand, with microalbuminuria, it has been observed an important rise in the prevalence of high blood pressure. This study stresses the importance of the relationship between subclinical proteinuria and microalbuminuria, on one hand, and arterial hypertension on the other hand. There have been studied 343 diabetics hospitalized in our Clinic. We estimated the presence of hypertension (according to WHO criteria) and the values of subclinical proteinuria (biuret method) and microalbuminuria (MICRAL-test). We observed that 70.8% of hypertensives and 49.4% of normotensives presented values of proteinuria that ranked between 300 and 500 mg/24 h (p < 0.001). Meanwhile, 25.8% of proteinuric patients and 14.8% of non-proteinuric ones were hypertensives (p < 0.05). In hypertensive diabetics the prevalence of subclinical proteinuria is higher than in normotensive ones. The prevalence of hypertension is significantly higher in microalbuminuric patients than in normoalbuminuric ones.

  4. 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.

  5. HIV related pulmonary arterial hypertension: epidemiology in Africa, physiopathology, and role of antiretroviral treatment.

    PubMed

    Bigna, Jean Joel R; Sime, Paule Sandra D; Koulla-Shiro, Sinata

    2015-01-01

    The development of HIV related pulmonary arterial hypertension (PAH) reduces the probability of survival by half as compared with HIV-infected individuals without HIV related PAH. HIV infected patients have a greater incidence of PAH compared to general population and have a 2500-fold increased risk of developing PAH. It is therefore important to have a recent overview of the problem in Africa, the most HIV affected part of the world (70 % of all HIV infection in the world). First, we discussed the epidemiology of HIV-related PAH in Africa. Second, the current understanding of the HIV-related PAH pathogenesis has been covered. Third, role of highly active antiretroviral therapy on HIV-related PAH has been revisited. There are few data concerning epidemiology of HIV related pulmonary hypertension in Africa leading to necessity to conduct further prospective large studies. The prevalence of PAH among HIV infected people in Africa varies from 5 to 13 %. The prevalence of HIV-related PAH in Africa is notably high compared to those in developed countries and in general population. The pathogenesis of PAH is clearly complex, and probably results from the interaction of multiple modulating genes with environmental factors. The physiopathology includes cytokines secretion increase which induces dysregulation of endothelial and vascular smooth muscle cell growth and imbalance of endogenous vasodilators and constrictors; HIV viral proteins which induces vascular oxidative stress, smooth myocyte proliferation and migration, and endothelial injury and genetic predisposition due to some major histocompatibility complex alleles, particularly HDL-DR6 and HLA-DR5. Histologically, HIV related PAH has the same characteristics with other types PAH. Antiretroviral therapy have a beneficial effect on the outcome of HIV related pulmonary hypertension, but it lacks evidence from large prospective studies.

  6. RNA Sequencing Analysis Detection of a Novel Pathway of Endothelial Dysfunction in Pulmonary Arterial Hypertension

    PubMed Central

    Rhodes, Christopher J.; Im, Hogune; Cao, Aiqin; Hennigs, Jan K.; Wang, Lingli; Sa, Silin; Chen, Pin-I; Nickel, Nils P.; Miyagawa, Kazuya; Hopper, Rachel K.; Tojais, Nancy F.; Li, Caiyun G.; Gu, Mingxia; Spiekerkoetter, Edda; Xian, Zhaoying; Chen, Rui; Zhao, Mingming; Kaschwich, Mark; del Rosario, Patricia A.; Bernstein, Daniel; Zamanian, Roham T.; Wu, Joseph C.; Snyder, Michael P.

    2015-01-01

    Rationale: Pulmonary arterial hypertension is characterized by endothelial dysregulation, but global changes in gene expression have not been related to perturbations in function. Objectives: RNA sequencing was used to discriminate changes in transcriptomes of endothelial cells cultured from lungs of patients with idiopathic pulmonary arterial hypertension versus control subjects and to assess the functional significance of major differentially expressed transcripts. Methods: The endothelial transcriptomes from the lungs of seven control subjects and six patients with idiopathic pulmonary arterial hypertension were analyzed. Differentially expressed genes were related to bone morphogenetic protein type 2 receptor (BMPR2) signaling. Those down-regulated were assessed for function in cultured cells and in a transgenic mouse. Measurements and Main Results: Fold differences in 10 genes were significant (P < 0.05), four increased and six decreased in patients versus control subjects. No patient was mutant for BMPR2. However, knockdown of BMPR2 by siRNA in control pulmonary arterial endothelial cells recapitulated 6 of 10 patient-related gene changes, including decreased collagen IV (COL4A1, COL4A2) and ephrinA1 (EFNA1). Reduction of BMPR2-regulated transcripts was related to decreased β-catenin. Reducing COL4A1, COL4A2, and EFNA1 by siRNA inhibited pulmonary endothelial adhesion, migration, and tube formation. In mice null for the EFNA1 receptor, EphA2, versus control animals, vascular endothelial growth factor receptor blockade and hypoxia caused more severe pulmonary hypertension, judged by elevated right ventricular systolic pressure, right ventricular hypertrophy, and loss of small arteries. Conclusions: The novel relationship between BMPR2 dysfunction and reduced expression of endothelial COL4 and EFNA1 may underlie vulnerability to injury in pulmonary arterial hypertension. PMID:26030479

  7. Novel dual endothelin receptor antagonist macitentan reverses severe pulmonary arterial hypertension in rats.

    PubMed

    Kunita-Takanezawa, Mutsumi; Abe, Kohtaro; Hirooka, Yoshitaka; Kuwabara, Yukimitsu; Hirano, Katsuya; Oka, Masahiko; Sunagawa, Kenji

    2014-11-01

    The efficacy of endothelin (ET) receptor antagonist bosentan in patients with severe pulmonary arterial hypertension (PAH) remains limited, partly because its higher doses for potential blockade of ET receptors have never been tested due to liver dysfunction. We hypothesized that rigorous blockade of ET receptors using the novel dual ET receptor antagonist macitentan would be effective in treating severe PAH without major side effects in a preclinical model appropriately representing the human disorder. In normal rats, 30 mg·kg·d of macitentan completely abolished big ET-1-induced increases in right ventricle (RV) systolic pressure. Adult male rats were injected with SU5416, a vascular endothelial growth factor blocker, and exposed to hypoxia for 3 weeks and then to normoxia for an additional 5 weeks (total 8 weeks). In intrapulmonary arterial rings isolated from rats with severe PAH, macitentan concentration dependently inhibited ET-1-induced contraction. Long-term treatment with macitentan (30 mg·kg·d, from week 3 to 8) reversed the high RV systolic pressure with preserved cardiac output. Development of RV hypertrophy, luminal occlusive lesions and medial wall thickening were also significantly improved without increasing serum levels of liver enzymes by macitentan. In conclusion, efficacious blockade of ET receptors with macitentan would reverse severe PAH without major adverse effects.

  8. [Regional characteristics of arterial hypertension in adult population of Croatia].

    PubMed

    Erceg, Marijan; Hrabak-Zerjavić, Vlasta; Ivicević Uhernik, Ana

    2007-06-01

    between the east and south, west and City of Zagreb should be investigated. In the high blood pressure group, 76.5% of subjects had a body mass index greater than 25 and 48% ofthose with inadequate physical activity, both exceeding the rates recorded in persons with normal blood pressure. Whereas 58.6% of the subjects knew they had elevated blood pressure, 48.4% of them were taking their therapy, and only 14.8% kept their blood pressure under control (systolic <140 mm Hg and diastolic <90 mm Hg). Arterial hypertension is a major public health problem in all regions of Croatia. The available literature data suggest that the Croatia's share of individuals with high blood pressure is comparable to that in industrialized countries of continental Europe. The prevention of excessive body weight, also through increased physical activity of the population and changes in poor dietary habits, remains the essential element in planning primary prevention programs for high blood pressure. Raising the population's awareness of the problem, early detection of high blood pressure and encouraging the population to take regular therapy for high blood pressure, along with the adoption of healthy lifestyle are important factors in achieving effective control and alleviating the consequences of hypertension.

  9. Arterial compliance in a group of normotensive and untreated hypertensive Cameroonian subjects in Yaounde

    PubMed Central

    Kingue, Samuel; Walinjom, Joshua; Menanga, Alain; Mintom, Pierre; Ngweth, Marie Ntep; Betrand, Fesuh; Muna, Walinjom

    2016-01-01

    Introduction Arterial compliance is an independent predictor of cardiovascular events. It decreases with age and this decrease is accelerated by hypertension. The objectives were to determine the arterial compliance in a group of normotensive and untreated hypertensive stage 1, 2 and 3 Cameroonian subjects. Methods A cross-sectional study was conducted from August 2012 to February 2013 in Yaoundé. Our sample size was 88 participants. The PulsePen® device was used to determine cfPWV (carotid-femoral Pulse Wave Velocity) and central Augmentation Index % (AIx). Other measurements obtained were: blood pressure (BP), body mass index (BMI), fasting glycaemia, lipid profile and serum creatinine. Results Our sample's mean age was 35.48 years and ranged from 20 to 60 years. The means of: cfPWV, SBP, DBP, Pulse Pressure (PP) and Heart Rate (HR) showed a statistically significant increase (p-value < 0.05) across the groups from normotensive to severely hypertensive patients. cfPWV was significantly correlated (p-value< 0.05) to: Age, Central SBP, Central DBP, Central PP, HR, BMI and central Augmentation index (AIx). Furthermore, cfPWV was significantly dependent on LVH (p-value <0.05). Conclusion This study suggests that arterial compliance decreases with increase severity of hypertension, indicating a higher risk of developing cardiovascular events in severely hypertensive patients. PMID:27795760

  10. Endothelium-derived Relaxing Factors of Small Resistance Arteries in Hypertension.

    PubMed

    Kang, Kyu-Tae

    2014-09-01

    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

  11. [Chronobiologic approaches to diagnosis of arterial hypertension in the Far North].

    PubMed

    Salamatina, L V; Buganov, A A; Umanskaia, E L; Ievleva, G I

    2003-01-01

    Epidemiologic examination of able-bodied population in Far North revealed time-matched averages and confidence intervals for systolic and diastolic blood pressure, pulse rate in newcomers, individuals with normal and high blood pressure. Those results enable to diagnose arterial hypertension by time-related changes in blood pressure during epidemiologic studies.

  12. Splenic Artery Embolization as an Adjunctive Procedure for Portal Hypertension

    PubMed Central

    Smith, Mitchell; Ray, Charles E.

    2012-01-01

    Splenic embolization is a technique that can be used alone or in conjunction with other treatments for the mitigation of portal hypertension and associated physiological effects of portal hypertension. This technique can be used safely when total embolization volume is ~50% and the procedural and periprocedural time periods are covered with antibiotics. In this patient population, partial splenic embolization can decrease the incidence of variceal bleeding, and protection can persist for at least a year. Additionally, liver function tests and serum cell counts can be expected to improve. Although not frequently used as primary therapy for patients with portal hypertension, splenic embolization can often be helpful as an alternative or adjunctive procedure. PMID:23729984

  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. Elevated Aminopeptidase P Attenuates Cerebral Arterial Responses to Bradykinin in Fawn-Hooded Hypertensive Rats.

    PubMed

    Hye Khan, Md Abdul; Sharma, Amit; Rarick, Kevin R; Roman, Richard J; Harder, David R; Imig, John D

    2015-01-01

    Cerebral arterial myogenic and autoregulatory responses are impaired in Fawn Hooded hypertensive (FHH) rats. Cerebral autoregulatory responses are restored in the congenic rat strain in which a segment of chromosome 1 from the Brown Norway (BN) rat was transferred into the FHH genetic background (FHH.1BN). The impact of this region on cerebral arterial dilator responses remains unknown. Aminopeptidase is a gene that was transferred into the FHH genetic background to generate the FHH.1BN rats and is responsible for degradation of the vasodilator bradykinin. Thus, we hypothesized that FHH rats will have increased aminopeptidase P levels with impaired cerebral arterial responses to bradykinin compared to BN and FHH.1BN rats. We demonstrated higher cerebral arterial expression of aminopeptidase P in FHH compared to BN rats. Accordingly, we demonstrated markedly impaired cerebral arterial dilation to bradykinin in FHH compared to BN rats. Interestingly, aminopeptidase P expression was lower in FHH.1BN compared to FHH rats. Decreased aminopeptidase P levels in FHH.1BN rats were associated with increased cerebral arterial bradykinin-induced dilator responses. Aminopeptidase P inhibition by apstatin improved cerebral arterial bradykinin dilator responses in FHH rats to a level similar to FHH.1BN rats. Unlike bradykinin, cerebral arterial responses to acetylcholine were similar between FHH and FHH.1BN groups. These findings indicate decreased bradykinin bioavailability contributes to impaired cerebral arterial dilation in FHH rats. Overall, these data indicate an important role of aminopeptidase P in the impaired cerebral arterial function in FHH rat.

  15. [CHANGES IN THE METABOLISM IN THE MYOCARDIUM OF RATS WITH ARTERIAL HYPERTENSION].

    PubMed

    Dovgan, R S; Zagorodnyi, M I

    2015-01-01

    In the myocardium of the rats with arterial hypertension marked increase in the amount of unsaturated fatty acids and polyunsaturated fatty acids. Reducing the concentration of palmitic acid and increased levels of arachidonic acid is considered as one of the factors that lead to the development of energy deficit and oxidative stress. In rats, with hypertension myocardial lactate concentration increases in the cytoplasmic fraction and reducing the amount of ATP. The level in the cytoplasmic and mitochondrial fractions above benchmarks, indicating about the change of antioxidant systems of the body In the cytoplasm and mitochondria of cardiomyocytes of the rats with arterial hypertension marked decrease in the activity of antioxidant enzymes: NO-synthase, catalase, glutathione reductase, which causes metabolic changes of the myocardium. PMID:27491168

  16. Mitochondrial energy conversion disturbance with decrease in ATP production as a source of systemic arterial hypertension.

    PubMed

    Postnov, Yuvenalii V; Orlov, Sergei N; Budnikov, Yegor Y; Doroschuk, Alexander D; Postnov, Anton Y

    2007-12-01

    Despite numerous efforts, including recent genetic and molecular biology studies, the immediate cause of stationary elevated blood pressure (BP) in any kind of hypertension has not been satisfactorily explained. This review deals with the cellular mechanisms underlying decreased energy status documented in different tissues from experimental rat models of primary and secondary hypertension as well as the involvement of these abnormalities in the pathogenesis of the disease. Such analyses allow us to hypothesize that dysfunction of mitochondrial energy conversion, caused by distinct stimuli, including generalized disturbances of intracellular Ca(2+) handling and mitochondria calcium overload found in primary hypertension, leads to uncoupling of oxidation and phosphorylation and attenuated ATP synthesis. Examples of arterial hypertension accompanied by mitochondrial uncoupling and cell ATP depletion (hyperthyroidism, cold hypertension, cyclosporine A intake, etc.) may be considered as an additional argument supporting this opinion. It means also that despite of differences in triggering mechanisms of mitochondrial dysfunction in all these models, the final outcome, i.e. decreased mitochondrial ATP production, is similar. Attenuated intracellular ATP content, in turn, results in the long-term maintenance of elevated BP by increased sympathetic outflow, whereas augmented ROS production following mitochondrial dysfunction lowers the capacity of the NO-dependent vascular relaxation. In the light of these data the cause of stationary elevated BP in chronic arterial hypertension should be regarded as a compensatory response to decreased mitochondrial ATP synthesis.

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

    PubMed

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

    2016-05-27

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

  18. Invited Commentary: Hypertension and Arterial Stiffness--Origins Remain a Dilemma.

    PubMed

    Jacobs, David R; Duprez, Daniel A; Shimbo, Daichi

    2016-04-01

    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.

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

    PubMed

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

    2016-01-01

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

  20. The Effects and Mechanism of Atorvastatin on Pulmonary Hypertension Due to Left Heart Disease

    PubMed Central

    Wang, Qing; Guo, Yi-Zhan; Zhang, Yi-Tao; Xue, Jiao-Jie; Chen, Zhi-Chong; Cheng, Shi-Yao; Ou, Mao-De; Cheng, Kang-Lin; Zeng, Wei-Jie

    2016-01-01

    Background Pulmonary hypertension due to left heart disease (PH-LHD) is one of the most common forms of PH, termed group 2 PH. Atorvastatin exerts beneficial effects on the structural remodeling of the lung in ischemic heart failure. However, few studies have investigated the effects of atorvastatin on PH due to left heart failure induced by overload. Methods Group 2 PH was induced in animals by aortic banding. Rats (n = 20) were randomly divided into four groups: a control group (C), an aortic banding group (AOB63), an atorvastatin prevention group (AOB63/ATOR63) and an atorvastatin reversal group (AOB63/ATOR50-63). Atorvastatin was administered for 63 days after banding to the rats in the AOB63/ATOR63 group and from days 50 to 63 to the rats in the AOB63/ATOR50-63 group. Results Compared with the controls, significant increases in the mean pulmonary arterial pressure, pulmonary arteriolar medial thickening, biventricular cardiac hypertrophy, wet and dry weights of the right middle lung, percentage of PCNA-positive vascular smooth muscle cells, inflammatory infiltration and expression of RhoA and Rho-kinase II were observed in the AOB63 group, and these changes concomitant with significant decreases in the percentage of TUNEL-positive vascular smooth muscle cells. Treatment of the rats in the AOB63/ATOR63 group with atorvastatin at a dose of 10 mg/kg/day significantly decreased the mean pulmonary arterial pressure, right ventricular hypertrophy, pulmonary arteriolar medial thickness, inflammatory infiltration, percentage of PCNA-positive cells and pulmonary expression of RhoA and Rho-kinase II and significantly augmented the percentage of TUNEL-positive cells compared with the AOB63 group. However, only a trend of improvement in pulmonary vascular remodeling was detected in the AOB63/ATOR50-63 group. Conclusions Atorvastatin prevents pulmonary vascular remodeling in the PH-LHD model by down-regulating the expression of RhoA/Rho kinase, by inhibiting the

  1. 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.

  2. [Significance of a life style change in arterial hypertension].

    PubMed

    Müller, J F; Franz, I W

    1998-12-10

    Changes in lifestyle represent a rational, promising and low side effect means of lowering the blood pressure and reducing the cardiovascular risk in many hypertensives. The first measure in all over-weight hypertensives is weight reduction. Even when the ideal weight is not reached, this measure leads to a lasting decrease in blood pressure. Beyond a threshold of 30 mg alcohol per day in men (approximately three glasses of beer or two glasses of wine) and 20 mg alcohol per day in women, the consumption of alcohol leads to an increase in blood pressure. Although only some hypertensives respond to a restriction of salt, all hypertensives should limit their salt intake to 5 to 6 g daily. Endurance training is an important pillar of lifestyle change. That relaxation techniques lower blood pressure has not been confirmed by the results of relevant studies. What has been confirmed, however, is the benefit of extensive changes in lifestyle, including information on health, daily endurance training, healthy eating habits and reduction of alcohol intake.

  3. 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.

  4. Alterations in structure of elastic laminae of rat pulmonary arteries in hypoxic hypertension.

    PubMed

    Liu, S Q

    1996-11-01

    The effect of hypoxic hypertension on the remodeling process of the elastic laminae of the rat hilar pulmonary arteries (PAs) was studied by electron microscopy. Rats were exposed to hypoxia (10% O2) for periods of 0.5, 2,6,12,48,96,144, and 240 h. Changes in the structure of the PA elastic laminae were examined and analyzed with respect to changes in the PA wall tensile stress. The PA blood pressure increased rapidly within the first several hours of hypoxia and reached a stable level within 2 days, whereas the PA wall tensile stress increased initially due to elevated blood pressure and then decreased after 48 h due to vessel wall thickening and returned to the control level after 4 days. In association with these changes, the elastic laminae, which appeared homogeneous in normal control rats, changed into structures composed of randomly oriented filaments and edematous contents with an increase in the volume during the early period of hypoxia and regained their homogeneous appearance and normal volume after 4 days. The changes in the elastic laminae were correlated with changes in the tensile stress. These changes were associated with a transient decrease in the stiffness of the PAs. In hypoxic rats given nifedipine, no change was found in the blood pressure, the tensile stress, or the structure of the elastic laminae of the PAs despite continuous exposure to hypoxia. These results suggested that altered tensile stress in the PA wall played a critical role in the initiation and regulation of structural changes in the elastic laminae and that these changes might contribute to alterations in the mechanical properties of the PA in hypoxic hypertension. PMID:8941540

  5. Systemic and renal oxidative stress in the pathogenesis of hypertension: modulation of long-term control of arterial blood pressure by resveratrol

    PubMed Central

    Hamza, Shereen M.; Dyck, Jason R. B.

    2014-01-01

    Hypertension affects over 25% of the global population and is associated with grave and often fatal complications that affect many organ systems. Although great advancements have been made in the clinical assessment and treatment of hypertension, the cause of hypertension in over 90% of these patients is unknown, which hampers the development of targeted and more effective treatment. The etiology of hypertension involves multiple pathological processes and organ systems, however one unifying feature of all of these contributing factors is oxidative stress. Once the body's natural anti-oxidant defense mechanisms are overwhelmed, reactive oxygen species (ROS) begin to accumulate in the tissues. ROS play important roles in normal regulation of many physiological processes, however in excess they are detrimental and cause widespread cell and tissue damage as well as derangements in many physiological processes. Thus, control of oxidative stress has become an attractive target for pharmacotherapy to prevent and manage hypertension. Resveratrol (trans-3,5,4′-Trihydroxystilbene) is a naturally occurring polyphenol which has anti-oxidant effects in vivo. Many studies have shown anti-hypertensive effects of resveratrol in different pre-clinical models of hypertension, via a multitude of mechanisms that include its function as an anti-oxidant. However, results have been mixed and in some cases resveratrol has no effect on blood pressure. This may be due to the heavy emphasis on peripheral vasodilator effects of resveratrol and virtually no investigation of its potential renal effects. This is particularly troubling in the arena of hypertension, where it is well known and accepted that the kidney plays an essential role in the long term regulation of arterial pressure and a vital role in the initiation, development and maintenance of chronic hypertension. It is thus the focus of this review to discuss the potential of resveratrol as an anti-hypertensive treatment via

  6. Newly diagnosed hyperthyroidism in the 25th gestational week of pregnancy presenting with systolic arterial hypertension only.

    PubMed

    Zaveljcina, Janez; Legan, Mateja; Gaberšček, Simona

    2016-05-01

    We present a case of a 30-year-old woman diagnosed with arterial hypertension in the 25th week of pregnancy. Our search for secondary causes of arterial hypertension revealed hyperthyroid Hashimoto's thyroiditis (HT), which was treated with propilthiouracil. Three weeks after delivery, she was normotensive without medication. In the next four months, she developed hypothyroidism and treatment with L-thyroxine was started. In conclusion, in the second half of pregnancy, a hyperthyroid HT can occur - in spite of the well-known amelioration of autoimmune thyroid disorders in that period, and can be the only cause of arterial hypertension. PMID:26979941

  7. [Cardiovascular risk stratification and therapeutic implications in arterial hypertension].

    PubMed

    Handschin, Anja; Henny-Fullin, Katja; Buess, Daniel; Dieterle, Thomas

    2015-06-01

    To improve the prevention of cardiovascular complications and events in hypertensive patients, it is of major importance to estimate the patient's individual risk for cardiovascular events. Antihypertensive treatment should not only be based on blood pressure values anymore, but also on the patient's comorbidities and risk profile. Risk stratification takes into account cardiovascular risk factors, diabetes, asymptomatic organ damage and established cardiovascular or renal disease. The most important markers for asymptomatic organ damage which should be searched for are microalbuminuria and LVH. Current guidelines emphasize the importance of the adaption and selection of treatment according to asymptomatic and established organ damage and provide assistance for treatment decisions. They focus also on the different non-pharmacological therapy options and lifestyle modifications. The goal of this article is to summarize the most important innovations and to point out the importance of simple tools for the implementation of cardiovascular risk stratification in hypertensive patients.

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

    PubMed Central

    2013-01-01

    Background Reduced gas transfer in patients with pulmonary arterial hypertension (PAH) is traditionally attributed to remodeling and progressive loss of pulmonary arterial vasculature that results in decreased capillary blood volume available for gas exchange. Methods We tested this hypothesis by determination of lung diffusing capacity (DL) and its components, the alveolar capillary membrane diffusing capacity (Dm) and lung capillary blood volume (Vc) in 28 individuals with PAH in comparison to 41 healthy individuals, and in 19 PAH patients over time. Using single breath simultaneous measure of diffusion of carbon monoxide (DLCO) and nitric oxide (DLNO), DL and Dm were respectively determined, and Vc calculated. Dm and Vc were evaluated over time in relation to standard clinical indicators of disease severity, including brain natriuretic peptide (BNP), 6-minute walk distance (6MWD) and right ventricular systolic pressure (RVSP) by echocardiography. Results Both DLCO and DLNO were reduced in PAH as compared to controls and the lower DL in PAH was due to loss of both Dm and Vc (all p < 0.01). While DLCO of PAH patients did not change over time, DLNO decreased by 24 ml/min/mmHg/year (p = 0.01). Consequently, Dm decreased and Vc tended to increase over time, which led to deterioration of the Dm/Vc ratio, a measure of alveolar-capillary membrane functional efficiency without changes in clinical markers. Conclusions The findings indicate that lower than normal gas transfer in PAH is due to loss of both Dm and Vc, but that deterioration of Dm/Vc over time is related to worsening membrane diffusion. PMID:23339456

  9. Progressive right ventricular functional and structural changes in a mouse model of pulmonary arterial hypertension.

    PubMed

    Wang, Zhijie; Schreier, David A; Hacker, Timothy A; Chesler, Naomi C

    2013-12-01

    Right ventricle (RV) dysfunction occurs with progression of pulmonary arterial hypertension (PAH) due to persistently elevated ventricular afterload. A critical knowledge gap is the molecular mechanisms that govern the transition from RV adaptation to RV maladaptation, which leads to failure. Here, we hypothesize that the recently established mouse model of PAH, via hypoxia and SU5416 treatment (HySu), captures that transition from adaptive to maladaptive RV remodeling including impairments in RV function and decreases in the efficiency of RV interactions with the pulmonary vasculature. To test this hypothesis, we exposed C57BL6 male mice to 0 (control), 14, 21, and 28 days of HySu and then obtained synchronized RV pressure and volume measurements in vivo. With increasing HySu exposure duration, arterial afterload increased monotonically, leading to a continuous increase in RV stroke work, RV fibrosis, and RV wall stiffening (P < 0.05). RV contractility increased at 14 days of HySu exposure and then plateaued (P < 0.05). As a result, ventricular-vascular coupling efficiency tended to increase at 14 days and then decrease. Our results suggest that RV remodeling may begin to shift from adaptive to maladaptive with increasing duration of HySu exposure, which would mimic changes in RV function with PAH progression found clinically. However, for the duration of HySu exposure used here, no drop in cardiac output was found. We conclude that the establishment of a mouse model for overt RV failure due to PAH remains an important task. PMID:24744862

  10. Fat utilization and arterial hypertension in overweight/obese subjects

    PubMed Central

    2013-01-01

    Background The Respiratory Quotient is a parameter reflecting the utilization of the nutrients by a subject. It is associated with an high rate of subsequent weight gain and with the atherosclerosis. Subjects tending to burn less fat have an increased Respiratory Quotient. Aim of this study was to investigate on the relationship between the Respiratory Quotient and the cardiovascular risk factors. Methods In this cross-sectional study we enrolled 223 individuals of both sexes aged 45–75 ys that were weight stable, receiving a balanced diet, and not affected by debilitating disease or cardiovascular disease. The Respiratory Quotient was measured by Indirect Calorimetry. The measurement of the Blood Pressure was obtained by a mercury sphygmomanometer. Results We enrolled 133 female and 90 male. Systolic blood pressure only was positively correlated to the Respiratory Quotient in univariate and multivariate regression analysis (p=0,017). The prevalence of hypertension was significatively different between the quartiles of the Respiratory Quotient, with the highest prevalence in the IV quartile (p=0,024). Conclusion High value of the Respiratory Quotient, an index of nutrients utilization, is associated to an high prevalence of Hypertension. It is possible that in the subjects with high Respiratory Quotient and high body mass index, the activation of the renin angiotensin system, in concert to the reduction of the utilization of the endogenous fat stores, could increase the risk of hypertension. PMID:23815947

  11. [Systemic arterial hypertension in the elderly. Recommendations for clinical practice].

    PubMed

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

    2016-01-01

    Hypertension is common in people aged 65 and older. In those aged 70 and older, hypertension is more poorly controlled than in those whose age is between 60 and 69 years. The number of trials available concerning the elderly population is limited; therefore, strong recommendations on blood pressure (BP) goals are limited. The American College of Cardiology has recently published a consensus report of management of hypertension in the elderly population. This review presents an overview of that consensus report and reviews specific studies that provide some novel findings regarding BP goals and the progression of nephropathy. In general, the evidence strongly supports a BP goal < 150/80 mm Hg for the elderly with scant data in those aged 80 and older. However, it was decided to set the goal < 140/90 mm Hg, unless the patient cannot tolerate it, and then try to achieve 140-145 mm Hg. Diuretics and calcium antagonists are the most efficient treatment; however, most patients will require two or more drugs to achieve such goals.

  12. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension

    PubMed Central

    Muñoz-Durango, Natalia; Fuentes, Cristóbal A.; Castillo, Andrés E.; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E.; Kalergis, Alexis M.

    2016-01-01

    Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage. PMID:27347925

  13. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension.

    PubMed

    Muñoz-Durango, Natalia; Fuentes, Cristóbal A; Castillo, Andrés E; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E; Kalergis, Alexis M

    2016-06-23

    Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage.

  14. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension.

    PubMed

    Muñoz-Durango, Natalia; Fuentes, Cristóbal A; Castillo, Andrés E; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E; Kalergis, Alexis M

    2016-01-01

    Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage. PMID:27347925

  15. Sodium hydrosulfide prevents hypoxia-induced pulmonary arterial hypertension in broilers.

    PubMed

    Yang, Y; Zhang, B K; Liu, D; Nie, W; Yuan, J M; Wang, Z; Guo, Y M

    2012-01-01

    1. The aim of the study was to determine if H(2)S is involved in the development of hypoxia-induced pulmonary hypertension in broilers, a condition frequently observed in a variety of cardiac and pulmonary diseases. 2. Two-week-old broilers were reared under normoxic conditions or exposed to normobaric hypoxia (6 h/day) with tissue levels of H(2)S adjusted by administering sodium hydrosulfide (NaHS, 10 µmol/kg body weight/day). Mean pulmonary arterial pressure, right ventricular mass, plasma and tissue H(2)S levels, the expression of cystathionine-β-synthase (CSE) and vascular remodeling were determined at 35 d of age. 3. Exposure to hypoxia-induced pulmonary arterial hypertension was characterized by elevated pulmonary pressure, right ventricular hypertrophy and vascular remodeling. This was accompanied by decreased expression of CSE and decreased concentrations of plasma and tissue H(2)S. 4. Hypoxia-induced pulmonary hypertension was significantly reduced by administration of NaHS but this protective effect was largely abolished by D, L-propargylglycerine, an inhibitor of CSE. 5. The results indicate that H(2)S is involved in the development of hypoxia-induced pulmonary hypertension. Supplementing NaHS or H(2)S could be a strategy for reducing hypoxia-induced hypertension in broilers.

  16. Subclinical arterial and cardiac damage in white-coat and masked hypertension.

    PubMed

    Wojciechowska, Wiktoria; Stolarz-Skrzypek, Katarzyna; Olszanecka, Agnieszka; Klima, Łukasz; Gąsowski, Jerzy; Grodzicki, Tomasz; Kawecka-Jaszcz, Kalina; Czarnecka, Danuta

    2016-08-01

    The study aimed to compare arterial and echocardiographic parameters in subjects with newly diagnosed masked (MH) or white-coat hypertension (WCH) to subjects with sustained normotension or sustained hypertension, defined according to the 2014 European Society of Hypertension practice guidelines for ambulatory blood pressure (BP) monitoring. We recruited 303 participants (mean age 46.9 years) in a family-based population study. SpaceLabs monitors and oscillometric sphygmomanometers were used to evaluate ambulatory and office BP, respectively. Central pulse pressure (PP) and aortic pulse-wave velocity (PWV) were measured with pulse-wave analysis (SphygmoCor software). Carotid intima-media thickness (IMT) and cardiac evaluation were assessed by ultrasonography. Analysing participants without antihypertensive treatment (115 sustained normotensives, 41 sustained hypertensives, 20 with WCH, 25 with MH), we detected significantly higher peripheral and central PP, PWV, IMT and left ventricular mass index in hypertensive subgroups than in those with sustained normotension. The differences between categories remained significant for peripheral PP and PWV after adjustment for confounding factors, including 24 h systolic and diastolic BP. Participants with WCH and MH, defined according to strict criteria, had more pronounced arterial and heart involvement than normotensive participants. The study demonstrates a high prevalence of these conditions in the general population that deserves special attention from physicians. PMID:26953075

  17. [Mitochondrial energy conversion disturbance with decrease in ATP production as a source of systemic arterial hypertension].

    PubMed

    Postnov, Iu V; Orlov, S N; Budnikov, E Iu; Doroshchuk, A D; Postnov, A Iu

    2008-01-01

    This review deals with the cellular mechanisms underlying decreased energy status documented in different tissues from experimental rat models of primary and secondary hypertension as well as the involvement of these abnormalities in the pathogenesis of the disease. Such analyses allow us to hypothesize that dysfunction of mitochondrial energy conversion, caused by distinct stimuli, including generalized disturbances of intracellular Ca2+ handling and mitochondria calcium overload found in primary hypertension, leads to uncoupling of oxidation and phosphorylation and attenuated ATP synthesis. Examples of arterial hypertension accompanied by mitochondrial uncoupling and cell ATP depletion (hyperthyroidism, cold hypertension, cyclosporine A intake, etc.) may be considered as an additional argument supporting this opinion. It means also that despite of differences in triggering mechanisms of mitochondrial dysfunction in all these models, the final outcome, i.e. decreased mitochondrial ATP production, is similar. Attenuated intracellular ATP content, in turn, results in the long-term maintenance of elevated BP by increased sympathetic outflow, whereas augmented ROS production following mitochondrial dysfunction lowers the capacity of the NO-dependent vascular relaxation. In the light of these data the cause of stationary elevated BP in chronic arterial hypertension should be regarded as a compensatory response to decreased mitochondrial ATP synthesis.

  18. [Update on the pathomorphological assessment of vasculopathies in pulmonary arterial hypertension].

    PubMed

    Dorfmüller, P; Humbert, M; Capron, F

    2006-03-01

    Pulmonary arterial hypertension (PAH) is a term which has recently been redefined and includes idiopathic pulmonary arterial hypertension, familial pulmonary arterial hypertension PAH related to specific pathological conditions (e.g. connective tissue diseases), as well as PAH caused by veno-occlusive disease or capillary hemangiomatosis. The clinical manifestation seems to be related to a peculiar pathological anatomy involving small, muscular pulmonary arteries, capillaries and veins. In addition to common hypertrophy of the tunica media, other vascular compartments may also be affected by intimal thickening or adventitial fibrosis. Moreover, complex lesions, such as so called plexiform lesions and arteritis can be present in certain forms of the disease. While the recent identification of responsible gene mutations in subgroups of patients have shed some light on disease evolution, therapeutic strategies must currently rely on vasodilative and antimitogenic drugs acting on the intimal and medial level of the affected pulmonary vessels. The clinical outcome of patients suffering from PAH remains poor, underlining our need for a better comprehension of disease pathophysiology, and thus for the characterization of specific histomorphological patterns.

  19. Pulmonary Arterial Hypertension Associated with Congenital Portosystemic Shunts Treated with Transcatheter Embolization and Pulmonary Vasodilators.

    PubMed

    Sato, Haruka; Miura, Masanobu; Yaoita, Nobuhiro; Yamamoto, Saori; Tatebe, Shunsuke; Aoki, Tatsuo; Satoh, Kimio; Ota, Hideki; Takase, Kei; Sugimura, Koichiro; Shimokawa, Hiroaki

    2016-01-01

    Cardiopulmonary abnormalities are often present in patients with liver diseases. We herein report a case of congenital portosystemic shunts complicated by hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PoPH). A 57-year-old woman complained of dyspnea and was subsequently diagnosed with HPS and PoPH caused by congenital portosystemic shunts. Although shunt closure by transcatheter embolization was successfully performed, her dyspnea worsened and pulmonary artery pressure and pulmonary vascular resistance elevated. Conventional vasodilator therapy was started, resulting in an improvement of pulmonary hypertension (PH). In some patients with congenital portosystemic shunts, shunt closure could exacerbate PH, and vasodilator therapy may be effective. PMID:27580545

  20. Risk Factors for Hemoptysis in Idiopathic and Hereditary Pulmonary Arterial Hypertension

    PubMed Central

    Tio, Darryl; Leter, Edward; Boerrigter, Bart; Boonstra, Anco; Vonk-Noordegraaf, Anton; Bogaard, Harm Jan

    2013-01-01

    Introduction When hemoptysis complicates pulmonary arterial hypertension (PAH), it is assumed to result from bronchial artery hypertrophy. In heritable PAH, the most common mutation is in the BMPR2 gene, which regulates growth, differentiation and apoptosis of mesenchymal cells. The aim of this study is to determine the relationship in PAH between the occurrence of hemoptysis, and disease progression, bronchial artery hypertrophy, pulmonary artery dilation and BMPR2 mutations. Methods 129 IPAH patients underwent baseline pulmonary imaging (CT angio or MRI) and repeated right-sided heart catheterization. Gene mutations were assessed in a subset of patients. Results Hemoptysis was associated with a greater presence of hypertrophic bronchial arteries and more rapid hemodynamic deterioration. The presence of a BMPR2 mutation did not predispose to the development of hemoptysis, but was associated with a greater number of hypertrophic bronchial arteries and a worse baseline hemodynamic profile. Conclusion Hemoptysis in PAH is associated with bronchial artery hypertrophy and faster disease progression. Although the presence of a BMPR2 mutation did not correlate with a greater incidence of hemoptysis in our patient cohort, its association with worse hemodynamics and a trend of greater bronchial arterial hypertrophy may increase the risk of hemoptysis. PMID:24194909

  1. Predictive value of middle cerebral artery to uterine artery pulsatility index ratio in hypertensive disorders of pregnancy.

    PubMed

    Adiga, Prashanth; Kantharaja, Indumathi; Hebbar, Shripad; Rai, Lavanya; Guruvare, Shyamala; Mundkur, Anjali

    2015-01-01

    Aims and Objectives. (i) To determine the predictive value of cerebrouterine (CU) ratio (middle cerebral artery to uterine artery pulsatility index, MCA/UT PI) in assessing perinatal outcome among hypertensive disorders of pregnancy. (ii) To compare between CU ratio and CP ratio (MCA/Umbilical artery PI) as a predictor of adverse perinatal outcome. Methods. A prospective observational study was done in a tertiary medical college hospital, from September 2012 to August 2013. One hundred singleton pregnancies complicated by hypertension peculiar to pregnancy were enrolled. Both CU and CP ratios were estimated. The perinatal outcomes were studied. Results. Both cerebrouterine and cerebroplacental ratios had a better negative predictive value in predicting adverse perinatal outcome. However, both CU and CP ratios when applied together were able to predict adverse outcomes better than individual ratios. The sensitivity, specificity, positive predictive value, and the negative predictive values for an adverse neonatal outcome with CU ratio were 61.3%, 70.3%, 56%, and 78.9%, respectively, compared to 42%, 57.5%, 62%, and 76% as with CP ratio. Conclusion. Cerebrouterine ratio and cerebroplacental ratio were complementary to each other in predicting the adverse perinatal outcomes. Individually, both ratios were reassuring for favorable perinatal outcome with high negative predictive value.

  2. Portal hypertension due to portal venous thrombosis: Etiology, clinical outcomes

    PubMed Central

    Harmanci, Ozgur; Bayraktar, Yusuf

    2007-01-01

    The thrombophilia in adult life has major implications in the hepatic vessels. The resulting portal vein thrombosis has various outcomes and complications. Esophageal varices, portal gastropathy, ascites, severe hypersplenism and liver failure needing liver transplantation are known well. The newly formed collateral venous circulation showing itself as pseudocholangicarcinoma sign and its possible clinical reflection as cholestasis are also known from a long time. The management strategies for these complications of portal vein thrombosis are not different from their counterpart which is cirrhotic portal hypertension, but the prognosis is unquestionably better in former cases. In this review we present and discuss the portal vein thrombosis, etiology and the resulting clinical pictures. There are controversial issues in nomenclature, management (including anticoagulation problems), follow up strategies and liver transplantation. In the light of the current knowledge, we discuss some controversial issues in literature and present our experience and our proposals about this group of patients. PMID:17552000

  3. 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.

  4. [Clinical and instrumental characteristics of primary high altitude arterial pulmonary hypertension].

    PubMed

    Mirrakhimov, M M; Rudenko, R I; Murataliev, T M; Khamzamulin, R O

    1976-10-01

    The clinical pattern of primary high altitude pulmonary arterial hypertension observed in permanent residents of mountain regions is described. The diagnostic value of some non-invasive instrumental methods in primary high altitude pulmonary artery hypertension is analysed: electro- and vectorcardiography, rheopulmonography, and indirect pulmonary artery pressure determination. It is suggested to distinguish the labile, stable and decompensated forms of the disease on the basis of its clinical and functional peculiarities. The criterion for the initial two forms consists in the persistence of the pulmonary artery pressure elevation, while the latter form is established when the high altitude cor pulmonale gets decompensated. Functional vasoconstriction of the pulmonary resistive vessels was shown to play an important role in the genesis of the disease: the administration of 0.5 mg of nitroglycerine and a 5-minute oxygen inhalation caused a positive dynamics in the indices of the pulmonary rheogramme and a reduction of the pulmonary artery pressure, which did not reach the level of the plane inhabitants, though.

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

    PubMed Central

    Papaioannou, Andriana I; Zakynthinos, Epaminondas; Kostikas, Konstantinos; Kiropoulos, Theodoros; Koutsokera, Angela; Ziogas, Athanasios; Koutroumpas, Athanasios; Sakkas, Lazaros; Gourgoulianis, Konstantinos I; Daniil, Zoe D

    2009-01-01

    Background The association between systemic sclerosis and pulmonary arterial hypertension (PAH) is well recognized. Vascular endothelial growth factor (VEGF) has been reported to play an important role in pulmonary hypertension. The aim of the present study was to examine the relationship between systolic pulmonary artery pressure, clinical and functional manifestations of the disease and serum VEGF levels in systemic sclerosis. Methods Serum VEGF levels were measured in 40 patients with systemic sclerosis and 13 control subjects. All patients underwent clinical examination, pulmonary function tests and echocardiography. Results Serum VEGF levels were higher in systemic sclerosis patients with sPAP ≥ 35 mmHg than in those with sPAP < 35 mmHg (352 (266, 462 pg/ml)) vs (240 (201, 275 pg/ml)) (p < 0.01), while they did not differ between systemic sclerosis patients with sPAP < 35 mmHg and controls. Serum VEGF levels correlated to systolic pulmonary artery pressure, to diffusing capacity for carbon monoxide and to MRC dyspnea score. In multiple linear regression analysis, serum VEGF levels, MRC dyspnea score, and DLCO were independent predictors of systolic pulmonary artery pressure. Conclusion Serum VEGF levels are increased in systemic sclerosis patients with sPAP ≥ 35 mmHg. The correlation between VEGF levels and systolic pulmonary artery pressure may suggest a possible role of VEGF in the pathogenesis of PAH in systemic sclerosis. PMID:19426547

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

    PubMed Central

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

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a rare and devastating disease characterized by progressive increases in pulmonary arterial pressure and pulmonary vascular resistance which eventually leads to right ventricular failure and death. Early thought process was that exercise and increased physical activity may be detrimental to PAH patients however many small cohort trials have proven otherwise. In addition to the many pharmaceutical options, exercise and pulmonary rehabilitation have also been shown to increase exercise capacity as well as various aspects of psychosomatic health. As pulmonary and exercise rehabilitation become more widely used as an adjuvant therapy patient outcomes improve and physicians should consider this in the therapeutic algorithm along with pharmacotherapy. PMID:25960979

  7. Renal artery thrombosis and hypertension in a 13 year old girl with antiphospholipid syndrome.

    PubMed Central

    Ostuni, P A; Lazzarin, P; Pengo, V; Ruffatti, A; Schiavon, F; Gambari, P

    1990-01-01

    The case of a 13 year old girl with renal artery thrombosis and hypertension is described. A cerebrovascular accident and a probable occlusion of the superior mesenteric artery also occurred. Very high levels of 'lupus anticoagulant', anticardiolipin antibodies as well as false positive Venereal Disease Research Laboratory tests were repeatedly shown. Moreover, the patient fulfilled at least four classification criteria for systemic lupus erythematosus, but only a slight positivity for antinucleolar antibodies was present. The striking relation between antiphospholipid antibody levels and clinical events and the treatment of this complex syndrome are discussed. Images PMID:2108619

  8. Comparison of nifedipine and captopril in children with pulmonary hypertension due to bronchopneumonia.

    PubMed

    Uner, A; Dogan, M; Demirtas, M; Açikgöz, M; Temel, H; Kaya, A; Caksen, H

    2008-10-01

    This study included 40 children, who were diagnosed with pneumonia and pulmonary hypertension (from the radiographic and clinical features), was performed at Yuzuncu Yil University Faculty of Medicine, Department of Pediatrics, from September 2003 to July 2005. Patients who had pneumonia and congenital heart disease or systemic hypertension or renal and liver disease together were excluded from the study. Blood gas analysis and oxygen concentration, measured with pulse oximetry, were performed in all patients. Besides chest X-ray, electrocardiography and echocardiographic search was also carried out. Echocardiographic examination was performed by using M mode, two-dimensional echocardiography and colored Doppler sonotron Vingmed CFM 725. At echocardiographic examination, pulmonary hypertension is defined as above 35 mmHg of pulmonary artery pressure. For echocardiographic examination, patients with pulmonary hypertension were divided into two groups. Captopril (2 mg/kg/day, three doses a day) and nifedipine (0.5 mg/kg/day, three doses a day) were given to the first and the second group, respectively. Echocardiography was performed daily until normal pulmonary artery pressure was achieved. At the beginning of the treatment, the patients were treated with double antibiotics and antibiotic change was carried out in needed cases at the follow up. Digoxin was administered to the cases of respiratory infection with heart failure. PMID:18304952

  9. Ascites due to pre-sinusoidal portal hypertension in dogs: a retrospective analysis of 17 cases.

    PubMed

    James, F E; Knowles, G W; Mansfield, C S; Robertson, I D

    2008-05-01

    Accumulation of a pure transudate abdominal effusion in the absence of significant hypoalbuminaemia is uncommon in dogs and is due to pre-sinusoidal portal hypertension. Reported causes of pre-sinusoidal portal hypertension vary, but suggest a reasonable prognosis. A retrospective analysis of 17 dogs that presented to our institution with ascites due to pre-sinusoidal portal hypertension identified idiopathic hepatic fibrosis or canine chronic hepatitis as the underlying cause in the majority of cases. Twelve (70.5%) dogs were 4 years of age or younger at time of presentation. Total serum protein was higher in dogs with chronic hepatitis than it was in dogs without inflammatory disease. The prognosis was generally poor and no histological, imaging or biochemical parameters were useful as prognostic indicators. Dogs died or were euthanased due to severe clinical signs associated with the portal hypertension and/or perceived poor prognosis.

  10. Interventional and surgical therapeutic strategies for pulmonary arterial hypertension: Beyond palliative treatments.

    PubMed

    Sandoval, Julio; Gomez-Arroyo, Jose; Gaspar, Jorge; Pulido-Zamudio, Tomas

    2015-10-01

    Despite significant advances in pharmacological treatments, pulmonary arterial hypertension remains an incurable disease with an unreasonably high morbidity and mortality. Although specific pharmacotherapies have shifted the survival curves of patients and improved exercise endurance as well as quality of life, it is also true that these pharmacological interventions are not always accessible (particularly in developing countries) and, perhaps most importantly, not all patients respond similarly to these drugs. Furthermore, many patients will continue to deteriorate and will eventually require an additional, non-pharmacological, intervention. In this review we analyze the role of atrial septostomy and Potts anastomosis in the management of patients with pulmonary arterial hypertension, we summarize the current worldwide clinical experience (case reports and case series), and discuss why these interventional/surgical strategies might have a therapeutic role beyond that of a "bridge" to transplantation.

  11. [Modern approaches to the use of neurotropic physical therapy in arterial hypertension].

    PubMed

    Orekhova, E M; Konchugova, T V; Kul'chitskaya, D B; Korchazhkina, N B; Egorova, L A; Chuich, N G

    2016-01-01

    The development and introduction into clinical practice of non-pharmacological methods for the prevention and treatment of arterial hypertension is a primary objective of modern physical therapy, especially as regards the neurotropic influences. This article was designed to report the results of the investigation into the hypotensive effect of transcerebral magnetic therapy obtained during the treatment of 60 patients presenting with arterial hypertension. The study included the comparative examination of two randomly formed groups containing 30 patients each. The patients of the main group received transcerebral magnetic therapy (to the frontal region) while those in the group of comparison were given magnetotherapy at the collar region. The study has demonstrated that transcerebral magnetic therapy given to the patients of the main group was a more efficient treatment than magnetotherapy at the collar region since it produced a more pronounced hypotensive effect irrespective of the initial hemodynamic type. PMID:27271835

  12. New Biochemical Insights into the Mechanisms of Pulmonary Arterial Hypertension in Humans.

    PubMed

    Bujak, Renata; Mateo, Jesús; Blanco, Isabel; Izquierdo-García, José Luis; Dudzik, Danuta; Markuszewski, Michał J; Peinado, Victor Ivo; Laclaustra, Martín; Barberá, Joan Albert; Barbas, Coral; Ruiz-Cabello, Jesús

    2016-01-01

    Diagnosis of pulmonary arterial hypertension (PAH) is difficult due to the lack of specific clinical symptoms and biomarkers, especially at early stages. We compared plasma metabolic fingerprints of PAH patients (n = 20) with matched healthy volunteers (n = 20) using, for the first time, untargeted multiplatform metabolomics approach consisting of high-performance liquid and gas chromatography coupled with mass spectrometry. Multivariate statistical analyses were performed to select metabolites that contribute most to groups' classification (21 from liquid in both ionization modes and 9 from gas chromatography-mass spectrometry). We found metabolites related to energy imbalance, such as glycolysis-derived metabolites, as well as metabolites involved in fatty acid, lipid and amino acid metabolism. We observed statistically significant changes in threitol and aminomalonic acid in PAH patients, which could provide new biochemical insights into the pathogenesis of the disease. The results were externally validated on independent case and control cohorts, confirming up to 16 metabolites as statistically significant in the validation study. Multiplatform metabolomics, followed by multivariate chemometric data analysis has a huge potential for explaining pathogenesis of PAH and for searching potential and new more specific and less invasive markers of the disease. PMID:27486806

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

    PubMed

    Schwaiger, Johannes P; Khanna, Dinesh; Gerry Coghlan, J

    2013-12-01

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

  14. New Biochemical Insights into the Mechanisms of Pulmonary Arterial Hypertension in Humans.

    PubMed

    Bujak, Renata; Mateo, Jesús; Blanco, Isabel; Izquierdo-García, José Luis; Dudzik, Danuta; Markuszewski, Michał J; Peinado, Victor Ivo; Laclaustra, Martín; Barberá, Joan Albert; Barbas, Coral; Ruiz-Cabello, Jesús

    2016-01-01

    Diagnosis of pulmonary arterial hypertension (PAH) is difficult due to the lack of specific clinical symptoms and biomarkers, especially at early stages. We compared plasma metabolic fingerprints of PAH patients (n = 20) with matched healthy volunteers (n = 20) using, for the first time, untargeted multiplatform metabolomics approach consisting of high-performance liquid and gas chromatography coupled with mass spectrometry. Multivariate statistical analyses were performed to select metabolites that contribute most to groups' classification (21 from liquid in both ionization modes and 9 from gas chromatography-mass spectrometry). We found metabolites related to energy imbalance, such as glycolysis-derived metabolites, as well as metabolites involved in fatty acid, lipid and amino acid metabolism. We observed statistically significant changes in threitol and aminomalonic acid in PAH patients, which could provide new biochemical insights into the pathogenesis of the disease. The results were externally validated on independent case and control cohorts, confirming up to 16 metabolites as statistically significant in the validation study. Multiplatform metabolomics, followed by multivariate chemometric data analysis has a huge potential for explaining pathogenesis of PAH and for searching potential and new more specific and less invasive markers of the disease.

  15. New Biochemical Insights into the Mechanisms of Pulmonary Arterial Hypertension in Humans

    PubMed Central

    Blanco, Isabel; Izquierdo-García, José Luis; Dudzik, Danuta; Markuszewski, Michał J.; Peinado, Victor Ivo; Laclaustra, Martín; Barberá, Joan Albert; Barbas, Coral

    2016-01-01

    Diagnosis of pulmonary arterial hypertension (PAH) is difficult due to the lack of specific clinical symptoms and biomarkers, especially at early stages. We compared plasma metabolic fingerprints of PAH patients (n = 20) with matched healthy volunteers (n = 20) using, for the first time, untargeted multiplatform metabolomics approach consisting of high-performance liquid and gas chromatography coupled with mass spectrometry. Multivariate statistical analyses were performed to select metabolites that contribute most to groups’ classification (21 from liquid in both ionization modes and 9 from gas chromatography-mass spectrometry). We found metabolites related to energy imbalance, such as glycolysis-derived metabolites, as well as metabolites involved in fatty acid, lipid and amino acid metabolism. We observed statistically significant changes in threitol and aminomalonic acid in PAH patients, which could provide new biochemical insights into the pathogenesis of the disease. The results were externally validated on independent case and control cohorts, confirming up to 16 metabolites as statistically significant in the validation study. Multiplatform metabolomics, followed by multivariate chemometric data analysis has a huge potential for explaining pathogenesis of PAH and for searching potential and new more specific and less invasive markers of the disease. PMID:27486806

  16. Abnormal structure and increased stiffness of the femoral arterial wall in young patients with sustained essential hypertension.

    PubMed

    Eiskjaer, H; Christensen, T; Pedersen, E B

    1989-10-01

    Thickness, elastic modulus, and stiffness of the common femoral arterial wall were estimated in 11 patients with essential hypertension and in 11 age-matched normotensive control subjects by use of an in vivo, non-invasive, ultrasound time-motion display technique (M-mode). Hypertensive patients had significantly higher levels than normotensive subjects with regard to arterial wall thickness (0.23 cm vs. 0.18 cm, medians; P less than 0.01), elastic modulus (10.6 x 10(7) Pa vs. 6.18 x 10(7) Pa, medians; P less than 0.05) and arterial wall stiffness (3.80 x 10(7) Pa vs. 2.07 +/- 10(7) Pa, medians; P less than 0.01). It is concluded that structural changes in the wall of the large arteries contribute to the increase in arterial wall stiffness in young patients with sustained essential hypertension.

  17. Spontaneous ophthalmic artery occlusion in children due to Hyperhomocysteinemia.

    PubMed

    Sachdeva, Virender; Garg, Ravi; Pathengay, Avinash; Kekunnaya, Ramesh

    2015-01-01

    Ophthalmic artery occlusion usually presents as a sudden onset profound decrease in vision in the middle-aged and elderly patients following periocular procedures (retrobulbar injection/glabellar fat injection), embolism from the heart or after prolonged systemic surgery. In this report, we describe three children with spontaneous ophthalmic artery occlusion who presented with unilateral loss of vision and diagnosed elsewhere as optic atrophy whose detailed history and examination were suggestive of ophthalmic artery occlusion. Detailed systemic and laboratory evaluation revealed hyperhomocysteinemia as the only potential risk factor. To the best of our knowledge, this is the first report of the association of hyperhomocysteinemia and spontaneous ophthalmic artery occlusion. PMID:26622143

  18. Veno-venous extracorporeal membrane oxygenation bridging to pharmacotherapy in pulmonary arterial hypertensive crisis.

    PubMed

    Srivastava, Mukta C; Ramani, Gautam V; Garcia, Jose P; Griffith, Bartley P; Uber, Patricia A; Park, Myung H

    2010-07-01

    We report the case of a treatment-naive patient with pulmonary arterial hypertension who presented with decompensated right ventricular failure and cardiogenic shock. Unstable hemodynamics, hypoxia and end-organ hypoperfusion limited up-titration of pharmacotherapy. Mechanical circulatory support with veno-venous extracorporeal membrane oxygenation (VV-ECMO) was initiated to permit dose titration of pulmonary vasodilator therapy. VV-ECMO was weaned after 10 days of support, with successful transition to intravenous epoprostenol and oral sildenafil.

  19. Veno-venous extracorporeal membrane oxygenation bridging to pharmacotherapy in pulmonary arterial hypertensive crisis.

    PubMed

    Srivastava, Mukta C; Ramani, Gautam V; Garcia, Jose P; Griffith, Bartley P; Uber, Patricia A; Park, Myung H

    2010-07-01

    We report the case of a treatment-naive patient with pulmonary arterial hypertension who presented with decompensated right ventricular failure and cardiogenic shock. Unstable hemodynamics, hypoxia and end-organ hypoperfusion limited up-titration of pharmacotherapy. Mechanical circulatory support with veno-venous extracorporeal membrane oxygenation (VV-ECMO) was initiated to permit dose titration of pulmonary vasodilator therapy. VV-ECMO was weaned after 10 days of support, with successful transition to intravenous epoprostenol and oral sildenafil. PMID:20417127

  20. Caregiver’s burden in pulmonary arterial hypertension: a clinical review

    PubMed Central

    Verma, Sameer; Sayal, Abhineet; Vijayan, V. K.; Rizvi, Syed M.; Talwar, Arunabh

    2016-01-01

    Caregiver’s burden is a multidimensional phenomenon affecting care-givers physically, emotionally and socially. It is critical to examine the burden of caregivers, because of the complex responsibility they have with their partners. There are relatively few studies that have examined factors linked with psychological burden amongst caregivers of pulmonary arterial hypertension (PAH) patients. Hence, it is pertinent to develop a good understanding of these factors and develop appropriate management strategies, modified to assist PAH caregivers. PMID:27807515

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

    PubMed Central

    2016-01-01

    Abstract Pulmonary hypertension (PH) predicts poor outcome in patients with left heart disease. A 62-year-old man was referred for heart failure associated with ischemic cardiomyopathy. He received a diagnosis of combined postcapillary and precapillary PH secondary to left heart disease on the basis of hemodynamic parameters. After the pulmonary artery denervation procedure was performed, hemodynamic parameters were markedly improved, which resulted in a significant increase in functional capacity. PMID:27252851

  2. High incidence of pulmonary arterial hypertension in systemic sclerosis patients with anti-centriole autoantibodies.

    PubMed

    Hamaguchi, Yasuhito; Matsushita, Takashi; Hasegawa, Minoru; Ueda-Hayakawa, Ikuko; Sato, Sinichi; Takehara, Kazuhiko; Fujimoto, Manabu

    2015-09-01

    Systemic sclerosis (SSc)-related autoantibodies are useful tools in identifying clinically homogenous subsets of patients and predicting their prognosis. In this report, we described five SSc patients with anti-centriole antibodies. All five patients were females and had digital ulcers/gangrene. Four of five (80%) patients had pulmonary arterial hypertension (PAH). None of the five patients had active pulmonary fibrosis or developed renal crisis. Anti-centriole antibodies may be a marker for PAH and digital ulcers/gangrene.

  3. [Systemic arterial hypertension in México. A consensus to mitigate its comorbidities].

    PubMed

    Pérez-Rodríguez, Gilberto

    2016-01-01

    Given that systemic arterial hypertension (SAH) is the most common illness presented by the adults who come to primary care in México, in this supplement a group of cardiologists, as well as other specialists, from the Instituto Mexicano del Seguro Social (IMSS) offer a systematic review, a critical analysis, and a national consensus of guidelines as a frame of reference to the daily clinical practice in order to mitigate SAH in México.

  4. Analysis of arterial wall remodeling in hypertension based on lamellar modeling.

    PubMed

    Taghizadeh, Hadi; Tafazzoli-Shadpour, Mohammad; Shadmehr, Mohammad B

    2015-09-01

    Arterial wall remodels its geometry and mechanical properties in response to hypertension to maintain functionality. The elevated pressure is sensed through cellular mechanotransduction pathways, and extra extracellular matrix is synthesized, leading to thickening and stiffening. The present study enquires the response of aortic lamellar structure to hypertensive blood pressure regarding unchanged circumferential stress "profile" across the media as remodeling criterion. We tested the hypothesis that alterations in the thickness of structural layers contributes to maintain stress profile with least deviation from normotensive conditions. To test this notion, finite element analysis was recruited to evaluate stress profile, considering wall residual stress, and lamellar structure was adjusted through an optimization algorithm. Our results indicated 47% increased thickness of the aortic media that originates from nonhomogenous thickening of the microstructural units. The thickening and stiffening responses of the wall tissue were coupled, and the optimized pattern of hypertension-induced remodeling was established. PMID:26369443

  5. Long-term Prognosis for Individuals with Hypertension Undergoing Coronary Artery Calcium Scoring

    PubMed Central

    Valenti, Valentina; Hartaigh, Bríain ó; Heo, Ran; Schulman-Marcus, Joshua; Cho, Iksung; Kalra, Dan K.; Truong, Quynh A.; Giambrone, Ashley E; Gransar, Heidi; Callister, Tracy Q.; Shaw, Leslee J.; Lin, Fay Y.; Chang, Hyuk-Jae; Sciarretta, Sebastiano; Min, James K

    2014-01-01

    Background To examine the performance of coronary artery calcification (CAC) for stratifying long-term risk of death in asymptomatic hypertensive patients. Methods and Results 8905 consecutive asymptomatic individuals without cardiovascular disease or diabetes who underwent CAC testing (mean age 53.3±10.5, 59.3% male) were followed for a mean of 14 years and categorized on the background of hypertension (in accordance with the 2014 Guidelines from the Joint National Committee 8) as well as age above or below 60 years. The prevalence and severity of CAC was higher for those with versus without hypertension (P<0.001), and the extent increased proportionally with advancing age (P<0.001). Following adjustment, the presence of CAC in patients above and below the age of 60 years was associated with worse prognosis for hypertensive (HR 7.74 [95% CI: 5.15-11.63] and HR 3.18 [95% CI: 2.42-4.19]) and normotensive (HR 4.83 [95% CI: 3.18-7.33] and HR 2.14 [95% CI: 1.61-2.85]), respectively. A zero CAC score was associated with a lower but persisting risk of mortality for hypertensives over the age of 60 years (HR 2.48 [95% CI: 1.50-4.08]); albeit, attenuating for those below the age of 60 years (P=0.09). In a “low risk” hypertensive population, a combined presence of hypertension and any CAC was associated with an almost five-fold (HR 4.68 [95% CI: 2.22-9.87]) risk of death. Conclusion Among asymptomatic hypertensive individuals, the presence and extent of CAC effectively identified individuals at heightened risk of mortality beyond conventional cardiovascular risk. PMID:25863296

  6. Diagnosis of pulmonary hypertension from radiographic estimates of pulmonary arterial size.

    PubMed Central

    Bush, A; Gray, H; Denison, D M

    1988-01-01

    The reported accuracy of radiographic measurements in predicting pulmonary hypertension is very variable. Measurements of right and left descending pulmonary artery diameter have been reported to provide a correct diagnosis in as many as 98% of patients. A study was carried out to determine the predictive value of measurements made from the chest radiographs of 50 normal subjects and of 27 patients undergoing right heart catheterisation for cardiac or pulmonary vascular disease, taking account of radiographic magnification. After such corrections a right descending pulmonary artery diameter over 16.7 mm or a left descending pulmonary artery diameter of over 16.9 mm distinguished 12 of 23 pulmonary hypertensive subjects, with no false positive results. The diameter was then arbitrarily squared (any differences between patients and control subjects being exaggerated) and the product was divided by either predicted or actual lung volume in an attempt to correct for body size. The new index distinguished 19 of 23 patients with pulmonary hypertension, with one false positive, when the divisor was actual lung volume; when predicted lung volume was used 18 of 23 patients were distinguished, again with one false positive result. PMID:3353884

  7. [Treatment of arterial hypertension in children and adolescents--Update of therapeutic options].

    PubMed

    Gilbert, Nadine; Hage, Alfred

    2015-04-01

    Changing living conditions, which lead to physical inactivity and obesity, are probably the main reason for the establishment of risk factors for cardiovascular diseases in children and adolescents. In the past those risk factors were typically seen only in the elderly. On long-term, the elevated body-mass-index is a very important risk factor for primary arterial hypertension in children and adolescents, because it is responsible for both structural and functional changes in the cardiovascular system. Regular screening for these target organ damages is necessary. However, the role of newer methods has still to be proven in current research. The primary therapeutical options for this group are life style interventions like body weight control and physical activity. Children and adolescents with arterial hypertension persisting despite life style interventions should receive medication early, in order to prevent persistent target organ damage. Drug therapy should start as mono therapy--depending on patient profile--with one ACE inhibitor, angiotensin II receptor antagonist, calcium channel blocker or beta-blocker. If blood pressure cannot be reduced into the target area by mono therapy, combination therapy with different mechanisms should be started. Forms of secondary arterial hypertension have to be treated according to the primary disease.

  8. [Treatment of arterial hypertension in children and adolescents--Update of therapeutic options].

    PubMed

    Gilbert, Nadine; Hage, Alfred

    2015-04-01

    Changing living conditions, which lead to physical inactivity and obesity, are probably the main reason for the establishment of risk factors for cardiovascular diseases in children and adolescents. In the past those risk factors were typically seen only in the elderly. On long-term, the elevated body-mass-index is a very important risk factor for primary arterial hypertension in children and adolescents, because it is responsible for both structural and functional changes in the cardiovascular system. Regular screening for these target organ damages is necessary. However, the role of newer methods has still to be proven in current research. The primary therapeutical options for this group are life style interventions like body weight control and physical activity. Children and adolescents with arterial hypertension persisting despite life style interventions should receive medication early, in order to prevent persistent target organ damage. Drug therapy should start as mono therapy--depending on patient profile--with one ACE inhibitor, angiotensin II receptor antagonist, calcium channel blocker or beta-blocker. If blood pressure cannot be reduced into the target area by mono therapy, combination therapy with different mechanisms should be started. Forms of secondary arterial hypertension have to be treated according to the primary disease. PMID:26364380

  9. [Parents' actions for prevention of arterial hypertension educational technology for health].

    PubMed

    Santos, Zélia Maria de Sousa Araújo; Caetano, Joselany Afio; Moreira, Francisco Getúlio Alves

    2011-11-01

    This participatory research aimed to evaluate behavioral changes in fifteen parents of pre-school children to prevent the risk factors of arterial hypertension, by applying education technology for health that is based on the Health Beliefs Model at a private school in Fortaleza, State of Ceará, Brazil. The field research was carried out through educational workshops and data collection through questionnaires and interviews. After organizing the data into categories, analysis was based on the premises of health education. Through the application of education technology for health, significant changes were observed in the parents' habits, besides the roles they assumed as agents of change and multipliers of educational actions in the family. Although difficulties arose in the process of change, the parents were motivated to prevent the risk factors of arterial hypertension in themselves and their children. Thus, education technology for health based on the Health Beliefs Model proved to be efficient, as significant behavioral changes occurred and the parents were motivated to prevent arterial hypertension by means of a healthy lifestyle.

  10. [Obesity as pathology of adipocytes: number of cells, volume of arterial bloodstream,local pools of circulation in vivo, natriuretic peptides and arterial hypertension].

    PubMed

    Titov, V N; Dmitriev, V A

    2015-03-01

    The non-specific systemic biological reaction of arterial pressure from the level of organism. vasomotor center and proximal section of arterial bloodstream is appealed to compensate disorders of metabolism and microcirculation in distal section of arteries. This phenomenon occurs in several cases. The primarily local disorders of metabolism at autocrine level, physiological (aphysiological) death of cells, "littering" of intercellular medium become the cause of disorder of microcirculation in paracrin cenosises and deteriorate realization of biological functions of homeostasis, trophology, endoecology and adaptation. The local compensation of affected perfusion in paracrin cenosises at the expense of function of peripheral peristaltic pumps, redistribution of local bloodflow in biological reaction of endothelium-depended vaso-dilation has no possibility to eliminate disorders in realization of biological functions. The systemic increase of arterial pressure under absence of specific symptoms of symptomatic arterial hypertension is a test to detect disorder of biological functions of homeostasis, trophology, biological function of endoecology and adaptation. Allforms of arterial hypertension develop by common algorithm independently from causes of disorders of blood flow, microcirculation in distal section of arteries. The non-specific systemic compensation ofdisorders of metabolism from level of organism, in proximal section of arterial bloodstream always is the same one and results in aphysiological alterations in organs-targets. To comprehend etiological characteristics of common pathogenesis of arterial hypertension is possible in case of application of such technically complicated and still unclear in differential diagnostic of deranged functions modes of metabolomics.

  11. Missed Total Occlusion Due to the Occipital Artery Arising from the Internal Carotid Artery

    SciTech Connect

    Ustunsoz, Bahri Gumus, Burcak; Koksal, Ali; Koroglu, Mert; Akhan, Okan

    2007-02-15

    A 56-year-old man was referred for digital subtraction angiography (DSA) with an ultrasound diagnosis of right proximal internal carotid artery (ICA) stenosis for possible carotid artery stenting. DSA revealed total occlusion of the ICA and an occipital artery arising from the stump and simulating continuation of the ICA. An ascending pharyngeal artery also arose from the same occipital artery. This case is of interest because this is a rare variation besides being a cause of misdiagnosis at carotid ultrasound.

  12. Similar Adiponectin Levels in Obese Normotensive and Obese Hypertensive Men and No Vasorelaxant Effect of Adiponectin on Human Arteries.

    PubMed

    Dreier, Rasmus; Asferg, Camilla; Berg, Jais O; Andersen, Ulrik B; Flyvbjerg, Allan; Frystyk, Jan; Linneberg, Allan; Jeppesen, Jørgen L; Edvinsson, Lars; Skovsted, Gry F

    2016-02-01

    Obesity is a strong risk factor for hypertension, but the mechanism linking obesity to hypertension is not fully elucidated. In obesity, circulating concentrations of adiponectin are decreased and hypoadiponectinaemia has in some but not all studies been associated with increased risk of hypertension. Due to this inconsistency, we decided to study adiponectin from two aspects in a cross-sectional in vivo study and in an experimental in vitro study. In the cross-sectional study, 103 men with body mass index (BMI) ≥ 30.0 kg/m(2) were studied; 63 had 24-hr ambulatory blood pressure (ABP) ≥ 130/80 mmHg (ObeseHT) and 40 had 24-hr ABP < 130/80 mmHg (ObeseNT). As controls, we studied 27 men with BMI between 20.0 and 24.9 kg/m(2) and 24-hr ABP < 130/80 mmHg (LeanNT). Serum concentrations of adiponectin and body composition using dual-energy X-ray absorptiometry scanning were determined. In vitro, the direct vasomotor response of adiponectin was tested on subcutaneous resistance arteries from human abdominal adipose tissue. The two obese groups had lower adiponectin concentrations compared with LeanNT (p < 0.01) [median (interquartile range)]: ObeseHT 6.5 (5.1-8.3) mg/L; ObeseNT 6.6 (5.2-7.8) mg/L; and LeanNT 9.4 (6.7-12.4) mg/L, with no significant difference in adiponectin concentrations (or body composition) between ObeseHT and ObeseNT (p = 0.67). In vitro, adiponectin did not have any direct vasodilatory effect and adiponectin did not affect angiotensin II-stimulated vasoconstriction. In conclusion, obese hypertensive men have similar serum concentrations of adiponectin as obese normotensive men. In combination with the in vitro data, these findings question a pathogenic role of adiponectin in human hypertension.

  13. Pulmonary Hypertension Due to Common Respiratory Conditions: Classification, Evaluation and Management Strategies

    PubMed Central

    Fein, Daniel G.; Zaidi, Ali N.; Sulica, Roxana

    2016-01-01

    Pulmonary hypertension (PH) due to chronic respiratory disease and/or hypoxia is classified as World Health Organization (WHO) Group III pulmonary hypertension. The patients most commonly encountered in clinical practice with group III PH include those with chronic obstructive lung disease (COPD), diffuse parenchymal lung disease, and sleep-disordered breathing. The purpose of this review is to outline the variable clinical significance of pulmonary hypertension in the most common pulmonary disease states and how a clinician may approach the management of these patients. PMID:27571110

  14. Pulmonary Hypertension Due to Common Respiratory Conditions: Classification, Evaluation and Management Strategies.

    PubMed

    Fein, Daniel G; Zaidi, Ali N; Sulica, Roxana

    2016-01-01

    Pulmonary hypertension (PH) due to chronic respiratory disease and/or hypoxia is classified as World Health Organization (WHO) Group III pulmonary hypertension. The patients most commonly encountered in clinical practice with group III PH include those with chronic obstructive lung disease (COPD), diffuse parenchymal lung disease, and sleep-disordered breathing. The purpose of this review is to outline the variable clinical significance of pulmonary hypertension in the most common pulmonary disease states and how a clinician may approach the management of these patients. PMID:27571110

  15. Hemodynamic, Functional, and Clinical Responses to Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension of Different Causes

    PubMed Central

    Zhang, Hang; Xie, Du-Jiang; Zhang, Juan; Zhou, Ling; Rothman, Alexander M.K.

    2015-01-01

    Background— The mechanisms underlying pulmonary arterial hypertension (PAH) are multifactorial. The efficacy of pulmonary artery denervation (PADN) for idiopathic PAH treatment has been evaluated. This study aimed to analyze the hemodynamic, functional, and clinical responses to PADN in patients with PAH of different causes. Methods and Results— Between April 2012 and April 2014, 66 consecutive patients with a resting mean pulmonary arterial pressure ≥25 mm Hg treated with PADN were prospectively followed up. Target drugs were discontinued after the PADN procedure. Hemodynamic response and 6-minute walk distance were repeatedly measured within the 1 year post PADN follow-up. The clinical end point was the occurrence of PAH-related events at the 1-year follow-up. There were no PADN-related complications. Hemodynamic success (defined as the reduction in mean pulmonary arterial pressure by a minimal 10% post PADN) was achieved in 94% of all patients, with a mean absolute reduction in systolic pulmonary arterial pressure and mean pulmonary arterial pressure within 24 hours of −10 mm Hg and −7 mm Hg, respectively. The average increment in 6-minute walk distance after PADN was 94 m. Worse PAH-related events occurred in 10 patients (15%), mostly driven by the worsening of PAH (12%). There were 8 (12%) all-cause deaths, with 6 (9%) PAH-related deaths. Conclusions— PADN was safe and feasible for the treatment of PAH. The PADN procedure was associated with significant improvements in hemodynamic function, exercise capacity, and cardiac function and with less frequent PAH-related events and death at 1 year after PADN treatment. Further randomized studies are required to confirm the efficacy of PADN for PAH. Clinical Trial Registration— URL: http://www.chictr.trc.com.cn. Unique identifier: chiCTR-ONC-12002085. PMID:26553699

  16. Hypertension

    PubMed Central

    LePine, Todd

    2012-01-01

    Hypertension is responsible for roughly one-in-six adult deaths annually in the United States and is associated with five of the top nine causes of death.1 Ten trillion dollars is the estimated annual cost worldwide of the direct and indirect effects of hypertension.2,3 In the U.S. alone, costs estimated at almost $74 billion in 2009 placed a huge economic burden on the health care system.4 The prevalence of hypertension increases with advancing age to the point where more than half of people 60 to 69 years of age and at least three-fourths of those 70 years of age and older are affected.5 Most individuals with hypertension do not have it adequately controlled.1,6 Medication noncompliance due to avoidance of side effects is suggested to be a primary factor.6 The epidemic incidence of hypertension and its significant cost to society indicate that a well-tolerated, cost-effective approach to treatment is urgently needed. PMID:24278815

  17. Hypertension.

    PubMed

    Fitzgerald, Kara; Lepine, Todd

    2012-05-01

    Hypertension is responsible for roughly one-in-six adult deaths annually in the United States and is associated with five of the top nine causes of death.(1) Ten trillion dollars is the estimated annual cost worldwide of the direct and indirect effects of hypertension.(2,3) In the U.S. alone, costs estimated at almost $74 billion in 2009 placed a huge economic burden on the health care system.(4) The prevalence of hypertension increases with advancing age to the point where more than half of people 60 to 69 years of age and at least three-fourths of those 70 years of age and older are affected.(5) Most individuals with hypertension do not have it adequately controlled.(1,6) Medication noncompliance due to avoidance of side effects is suggested to be a primary factor.(6) The epidemic incidence of hypertension and its significant cost to society indicate that a well-tolerated, cost-effective approach to treatment is urgently needed.

  18. Alpha 1-adrenoceptors mediating contraction in arteries of normotensive and spontaneously hypertensive rats are of the alpha 1D or alpha 1A subtypes.

    PubMed

    Villalobos-Molina, R; Ibarra, M

    1996-03-18

    Alpha 1-Adrenoceptor subtypes mediating contraction in carotid, aorta, mesenteric and caudal arteries from both Wistar Kyoto (WKY) normotensive and spontaneously hypertensive (SHR) rats were investigated by using the alpha 1A-adrenoceptor agonist methoxamine and antagonized with selective, competitive antagonists WB-4101, 5-methyl urapidil or BMY 7378 (8-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4,5)decane -7,9-dione dihydrochloride). Isometric tension changes were recorded after methoxamine addition to the arterial rings, and the effects of the antagonists determined. All the antagonists shifted to the right the concentration-response curve to methoxamine. pA2 values indicate that all arteries but caudal express the alpha 1D-adrenoceptor subtype, since BMY 7378 values were high in these arteries. Due to the high pA2 values for 5-methyl urapidil and WB-4101 and the low values for BMY 7378 we conclude that the tail artery expresses the alpha 1A and not the alpha 1B subtype. No differences were found between both strains of rats, suggesting that hypertension does not modify the alpha 1-adrenoceptors in conductance arteries. PMID:8846824

  19. Role of curcumin in idiopathic pulmonary arterial hypertension treatment: a new therapeutic possibility.

    PubMed

    Bronte, Enrico; Coppola, Giuseppe; Di Miceli, Riccardo; Sucato, Vincenzo; Russo, Antonio; Novo, Salvatore

    2013-11-01

    The idiopathic pulmonary arterial hypertension is a complex disease that mainly affects pulmonary arterial circulation. This undergoes a remodeling with subsequent reduction of flow in the small pulmonary arteries. Because of this damage an increased vascular resistance gradually develops, and over time it carries out in heart failure. The inflammatory process is a key element in this condition, mediated by various cytokines. The inflammatory signal induces activation of NF-κB, and prompts TGF-β-related signaling pathway. Clinical evolution leads to progressive debilitation, greatly affecting the patient quality of life. The actual therapeutic approaches, are few and expensive, and include systemic drugs such as prostanoids, phosphodiesterase inhibitors and antagonists of endothelin-1 (ERBs). Some researchers have long investigated the anti-inflammatory effects of curcumin. It shows a role for inactivation of NF-κB-mediated inflammation. On the basis of these findings we propose a potential role of curcumin and its pharmacologically fit derivatives for treatment of idiopathic pulmonary arterial hypertension.

  20. Beneficial effects of grape seed proanthocyanidin extract on arterial remodeling in spontaneously hypertensive rats via protecting against oxidative stress.

    PubMed

    Liang, Ying; Wang, Jian; Gao, Haiqing; Wang, Quanzhen; Zhang, Jun; Qiu, Jie

    2016-10-01

    Arterial remodeling is a pathogenic occurrence during hypertension and, in turn, is closely associated with the development and complications of hypertension. Grape seed proanthocyanidin extract (GSPE) has been reported to exhibit a protective effect on cardiovascular disease, however its effect on arterial remodeling remains to be fully elucidated. In the present study, the effects of GSPE on arterial remodeling were analyzed by treating spontaneously hypertensive rats (SHRs) with GSPE (250 mg/kg·day). Arterial remodeling was quantified through morphological methods; thoracic aortas were stained with hematoxylin-eosin or sirius red‑victoria blue. The arterial ultrastructure was imaged using transmission electron microscopy. The content of nitric oxide (NO) and endothelin‑1 (ET‑1) were examined to determine endothelial function. Oxidative stress was assessed by malondialdehyde (MDA) levels and the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Administration of GSPE markedly alleviated hypertension‑induced arterial remodeling, which was not associated with blood pressure control. ET‑1 production was reduced, while NO production was increased in the GSPE group, which exhibited improved endothelial function. In addition, treatment with GSPE significantly ameliorated oxidative stress by improving SOD and CAT activities and reducing MDA formation. In conclusion, GSPE may attenuate hypertension‑induced arterial remodeling by repressing oxidative stress and is recommended as a potential anti‑arterial remodeling agent for patients with hypertensive vascular diseases. PMID:27601315

  1. Aging in blood vessels. Medicinal agents FOR systemic arterial hypertension in the elderly.

    PubMed

    Rubio-Ruiz, María Esther; Pérez-Torres, Israel; Soto, María Elena; Pastelín, Gustavo; Guarner-Lans, Verónica

    2014-11-01

    Aging impairs blood vessel function and leads to cardiovascular disease. The mechanisms underlying the age-related endothelial, smooth muscle and extracellular matrix vascular dysfunction are discussed. Vascular dysfunction is caused by: (1) Oxidative stress enhancement. (2) Reduction of nitric oxide (NO) bioavailability, by diminished NO synthesis and/or augmented NO scavenging. (3) Production of vasoconstrictor/vasodilator factor imbalances. (4) Low-grade pro-inflammatory environment. (5) Impaired angiogenesis. (6) Endothelial cell senescence. The aging process in vascular smooth muscle is characterized by: (1) Altered replicating potential. (2) Change in cellular phenotype. (3) Changes in responsiveness to contracting and relaxing mediators. (4) Changes in intracellular signaling functions. Systemic arterial hypertension is an age-dependent disorder, and almost half of the elderly human population is hypertensive. The influence of hypertension on the aging cardiovascular system has been studied in models of hypertensive rats. Treatment for hypertension is recommended in the elderly. Lifestyle modifications, natural compounds and hormone therapies are useful for initial stages and as supporting treatment with medication but evidence from clinical trials in this population is needed. Since all antihypertensive agents can lower blood pressure in the elderly, therapy should be based on its potential side effects and drug interactions.

  2. CT-Base Pulmonary Artery Measurementin the Detection of Pulmonary Hypertension

    PubMed Central

    Shen, Yongchun; Wan, Chun; Tian, Panwen; Wu, Yanqiu; Li, Xiaoou; Yang, Ting; An, Jing; Wang, Tao; Chen, Lei; Wen, Fuqiang

    2014-01-01

    Abstract To summarize the performance of CT-based main pulmonary artery diameter or pulmonary artery to aorta ratio (PA:A ratio) measurement in detection of pulmonary hypertension by a systematic review and meta-analysis. A comprehensive literature search was performed to identify studies determining diagnostic accuracy of main pulmonary artery diameter or PA:A ratio measurement for pulmonary hypertension. The Quality Assessment of Diagnostic Accuracy Studies tool was used to assess the quality of the included studies. A bivariate random-effects model was used to pool sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), and diagnostic odds ratio (DOR). Summary receiver operating characteristic (SROC) curves and area under the curve (AUC) were used to summarize overall diagnostic performance. This meta-analysis included 20 publications involving 2134 subjects. Summary estimates for main pulmonary artery diameter measurement in the diagnosis of pulmonary hypertension were as follows: sensitivity, 0.79 (95% CI 0.72–0.84); specificity, 0.83 (95% CI 0.75–0.89); PLR, 4.68 (95% CI 3.13–6.99); NLR, 0.26 (95% CI 0.20–0.33); DOR, 18.13 (95% CI 10.87–30.24); and AUC 0.87. The corresponding summary performance estimates for using the PA:A ratio were as follows: sensitivity, 0.74 (95% CI 0.66–0.80); specificity, 0.81 (95% CI 0.74–0.86); PLR, 3.83 (95% CI, 2.70–5.43); NLR, 0.33 (95% CI 0.24–0.44); DOR, 11.77 (95% CI 6.60–21.00); and AUC 0.84. Both main pulmonary artery diameter and PA:A ratio are helpful for diagnosing pulmonary hypertension. Nevertheless, the results of pulmonary artery measurement should be interpreted in parallel with the results of traditional tests such as echocardiography. PMID:25501096

  3. Immune suppression prevents renal damage and dysfunction and reduces arterial pressure in salt-sensitive hypertension.

    PubMed

    Tian, N; Gu, J-W; Jordan, S; Rose, R A; Hughson, M D; Manning, R D

    2007-02-01

    The goal of this study was to test the hypothesis that renal infiltration of immune cells in Dahl S rats on increased dietary sodium intake contributes to the progression of renal damage, decreases in renal hemodynamics, and development of hypertension. We specifically studied whether anti-immune therapy, using mycophenolate mofetil (MMF), could help prevent increases in renal NF-kappaB activation, renal infiltration of monocytes/macrophages, renal damage, decreases in glomerular filtration rate (GFR) and renal plasma flow, and increases in arterial pressure. Seventy-four 7-to 8-wk-old Dahl S, Rapp strain rats were maintained on an 8% Na, 8% Na + MMF (20 mg.kg(-1).day(-1)), 0.3% Na, or 0.3% Na + MMF diet for 5 wk. Arterial and venous catheters were implanted at day 21. By day 35, renal NF-kappaB in 8% Na rats was 47% higher than in 0.3% Na rats and renal NF-kappaB was 41% lower in 8% Na + MMF rats compared with the 8% Na group. MMF treatment significantly decreased renal monocyte/macrophage infiltration and renal damage and increased GFR and renal plasma flow. In high-NA Dahl S rats mean arterial pressure increased to 182 +/- 5 mmHg, and MMF reduced this arterial pressure to 124 +/- 3 mmHg. In summary, in Dahl S rats on high sodium intake, treatment with MMF decreases renal NF-kappaB and renal monocyte/macrophage infiltration and improves renal function, lessens renal injury, and decreases arterial pressure. This suggests that renal infiltration of immune cells is associated with increased arterial pressure and renal damage and decreasing GFR and renal plasma flow in Dahl salt-sensitive hypertension.

  4. Survival protection by bodyweight in isolated scleroderma-related pulmonary artery hypertension.

    PubMed

    Marini, Carlo; Formichi, Bruno; Bauleo, Carolina; Michelassi, Claudio; Airò, Edoardo; Rossi, Giuseppe; Giuntini, Carlo

    2016-10-01

    In chronic heart failure (CHF) due to systemic cardiovascular disease, obese patients have better survival. Bodyweight versus survival was analyzed post hoc in subjects with limited scleroderma (SSc) and isolated pulmonary artery hypertension (PAH), i.e. with CHF due to pulmonary vascular disease. Rheumatologists referred scleroderma subjects for evaluation, and PAH was ascertained by right heart catheterization (RHC). Forty-nine SSc-PAH subjects were stratified by body mass index (BMI): obese 7 (14.3 %), overweight 11 (22.4 %), normal weight 21 (42.9 %), and underweight 10 (20.4 %) for 24-month follow-up and pooled together for long-term 72-month follow-up. Survival was analyzed by Kaplan-Meier method. Multivariate Cox proportional hazards modeling helped to assess variables associated to survival. At 24 months (17 events), survival increases with BMI across four groups (logrank for trend P = 0.031). By Cox multivariate mortality, best model included: BMI (P = 0.043), low lung diffusion (DLco, P = 0.007), and reduced stroke volume index (SVI, P = 0.017). At 72 month (37 events), higher BMI values were associated with better survival but not significantly (P = 0.076). By multivariate modeling BMI did not enter any model, whereas low DLco entered all (P < 0.001). Also low SVI (P = 0.02) and low mixed venous saturation (SvO2, P = 0.009) were associated with the prognosis. From PAH diagnosis to final event, BMI had small (5.4 %), but significant decline (P < 0.001). This is ascribed to CHF progression, and may explain BMI predictive power weakening. The results suggest BMI decline should be contrasted, DLco is useful for screening and with SVI and SvO2 for assessing prognosis and treatment.

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

    PubMed

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

    2008-10-01

    Extracellular matrix remodeling has been proposed as one mechanism by which proximal pulmonary arteries stiffen during pulmonary arterial hypertension (PAH). Although some attention has been paid to the role of collagen and metallomatrix proteins in affecting vascular stiffness, much less work has been performed on changes in elastin structure-function relationships in PAH. Such work is warranted, given the importance of elastin as the structural protein primarily responsible for the passive elastic behavior of these conduit arteries. Here, we study structure-function relationships of fresh arterial tissue and purified arterial elastin from the main, left, and right pulmonary artery branches of normotensive and hypoxia-induced pulmonary hypertensive neonatal calves. PAH resulted in an average 81 and 72% increase in stiffness of fresh and digested tissue, respectively. Increase in stiffness appears most attributable to elevated elastic modulus, which increased 46 and 65%, respectively, for fresh and digested tissue. Comparison between fresh and digested tissues shows that, at 35% strain, a minimum of 48% of the arterial load is carried by elastin, and a minimum of 43% of the change in stiffness of arterial tissue is due to the change in elastin stiffness. Analysis of the stress-strain behavior revealed that PAH causes an increase in the strains associated with the physiological pressure range but had no effect on the strain of transition from elastin-dominant to collagen-dominant behavior. These results indicate that mechanobiological adaptations of the continuum and geometric properties of elastin, in response to PAH, significantly elevate the circumferential stiffness of proximal pulmonary arterial tissue. PMID:18660454

  6. Hypertension - overview

    MedlinePlus Videos and Cool Tools

    If left untreated, hypertension can lead to the thickening of arterial walls causing its lumen, or blood passage way, to narrow in diameter. ... the narrowed arterial openings. In addition, people with hypertension may be more susceptible to stroke.

  7. Transglutaminase activity is decreased in large arteries from hypertensive rats compared with normotensive controls

    PubMed Central

    Johnson, Kyle B.; Hitomi, Kiyotaka; Tykocki, Nathan R.; Thompson, Janice M.; Watts, Stephanie W.

    2015-01-01

    Transglutaminases (TGs) catalyze the formation of covalent cross-links between glutamine residues and amine groups. This cross-linking activity has been implicated in arterial remodeling. Because hypertension is characterized by arterial remodeling, we hypothesized that TG activity, expression, and functionality would be increased in the aorta, but not in the vena cava (which does not undergo remodeling), from hypertensive rats relative to normotensive rats. Spontaneously hypertensive stroke-prone rats (SHRSP) and DOCA-salt rats as well as their respective normotensive Wistar-Kyoto or Sprague-Dawley counterparts were used. Immunohistochemistry and Western blot analysis measured the presence and expression of TG1 and TG2, in situ activity assays quantified active TGs, and isometric contractility was used to measure TG functionality. Contrary to our hypothesis, the activity (52% DOCA-salt vs. control rats and 56% SHRSP vs. control rats, P < 0.05), expression (TG1: 54% DOCA-salt vs. control rats, P > 0.05, and TG2: 77% DOCA-salt vs. control rats, P < 0.05), and functionality of TG1 and TG2 were decreased in the aorta, but not in the vena cava, from hypertensive rats. Mass spectrometry identified proteins uniquely amidated by TGs in the aorta that play roles in cytoskeletal regulation, redox regulation, and DNA/RNA/protein synthesis and regulation and in the vena cava that play roles in cytoskeletal regulation, coagulation regulation, and cell metabolism. Consistent with the idea that growing cells lose TG2 expression, vascular smooth muscle cells placed in culture lost TG2 expression. We conclude that the expression, activity, and functionality of TG1 and TG2 are decreased in the aorta, but not in the vena cava, from hypertensive rats compared with control rats. PMID:25599570

  8. Interventional Management of Massive Hemothorax Due to Inadvertent Puncture of an Aberrant Right Subclavian Artery

    SciTech Connect

    Jahnke, Thomas Schaefer, Phillip Jost; Heller, Martin; Mueller-Huelsbeck, Stefan

    2008-07-15

    We report a case of massive hemothorax due to inadvertent puncture of an aberrant right subclavian artery during central venous access. Iatrogenic laceration at the origin of the right internal thoracic artery was successfully treated with coil embolization of the internal thoracic artery followed by stent-graft placement into the subclavian artery. Due to its elongated and abnormal course, an aberrant right subclavian artery may predispose to inadvertent puncture during vein catheterization and should be recognized as a potential threat for such procedures. Our case emphasizes that ultrasound guidance should be used routinely for central venous lines wherever possible.

  9. Novel Therapeutic Targets for Phosphodiesterase 5 Inhibitors: current state-of-the-art on systemic arterial hypertension and atherosclerosis.

    PubMed

    Vasquez, Elisardo C; Gava, Agata L; Graceli, Jones B; Balarini, Camille M; Campagnaro, Bianca P; Pereira, Thiago Melo C; Meyrelles, Silvana S

    2016-01-01

    The usefulness of selective inhibitors of phosphodiesterase 5 (PDE5) is well known, first for the treatment of male erectile dysfunction and more recently for pulmonary hypertension. The discovery that PDE5 is present in the systemic artery endothelium and smooth muscle cells led investigators to test the extra sexual effects of sildenafil, the first and most investigated PDE5 inhibitor, in diseases affecting the systemic arteries. Cumulative data from experimental and clinical studies have revealed beneficial effects of sildenafil on systemic arterial hypertension and its target organs, such as the heart, kidneys and vasculature. An important effect of sildenafil is reduction of hypertension and improvement of endothelial function in experimental models of hypertension and hypertensive subjects. Interestingly, in angiotensin-dependent hypertension, its beneficial effects on endothelial and kidney dysfunctions seem to at least in part be caused by its ability to decrease the levels of angiotensin II and increase angiotensin 1-7, in addition to improving nitric oxide bioavailability and diminishing reactive oxygen species. Another remarkable finding on the effects of sildenafil comes from studies in apolipoprotein E knockout mice, a model of atherosclerosis that closely resembles human atherosclerotic disease. In this review, we focus on the promising beneficial effects of sildenafil for treating systemic high blood pressure, especially resistant hypertension, and the endothelial dysfunction that is present in hypertension and atherosclerosis.

  10. Prevalence and predictors of atherosclerotic renal artery stenosis in hypertensive patients undergoing simultaneous coronary and renal artery angiography; a cross-sectional study

    PubMed Central

    Payami, Babak; Jafarizade, Mehrian; Beladi Mousavi, Seyed Seifollah; Sattari, Shahab-Aldin; Nokhostin, Forough

    2016-01-01

    Introduction: According to the non-specific presentation of atherosclerotic renal artery stenosis (ARAS), this disease is usually an under-diagnosed in clinical conditions. Objectives: The aim of the presence study was to evaluate the prevalence of renal artery stenosis (RAS) and its related risk factors in hypertensive patients undergoing coronary angiography. Patients and Methods: In a cross-sectional study, between March 2009 and October 2010, all of hypertensive patients candidate for diagnostic cardiac catheterization, underwent nonselective renal angiography before completion of their coronary angiography procedure. A standardized questionnaire was used to collect demographics, cardiac history, indications for cardiac catheterization and angiographic data. The degree of ARAS was estimated visually by skilled cardiologist. Narrowing greater than 50% of the arterial lumen considered as arterial stenosis. Data was analyzed by SPSS version 19, and by chi-square test and logistic regression model. Results: In overall 274 patients with mean age of 60.75 ± 10.92 years 108 (39.4%) were male and 166 (60.61%) were female. The prevalence of ARAS calculated 18.2%. According to the present study, heart failure and smoking were predictors of ARAS. However, old age, gender, diabetes mellitus, hyperlipidemia and family history of cardiovascular disease were not clinical predictors of significant ARAS in hypertensive patients, candidate for coronary angiography. Conclusion: According to present data, we suggest to consider renal artery angiography in combination with coronary artery angiography especially in hypertensive patients who are smoker or individuals who have heart failure. PMID:27069966

  11. Endovascular solutions to arterial injury due to posterior spine surgery.

    PubMed

    Loh, Shang A; Maldonaldo, Thomas S; Rockman, Caron B; Lamparello, Patrick J; Adelman, Mark A; Kalhorn, Stephen P; Frempong-Boadu, Anthony; Veith, Frank J; Cayne, Neal S

    2012-05-01

    Iatrogenic arterial injury is an uncommon but recognized complication of posterior spinal surgery. The spectrum of injuries includes vessel perforation leading to hemorrhage, delayed pseudoaneurysm formation, and threatened perforation by screw impingement on arterial vessels. Repair of these injuries traditionally involved open direct vessel repair or graft placement, which can be associated with significant morbidity. We identified five patients with iatrogenic arterial injury during or after posterior spinal surgery between July 2004 and August 2009 and describe their endovascular treatment. Intraoperative arterial bleeding was encountered in two patients during posterior spinal surgery. The posterior wounds were packed, temporarily closed, and the patient was placed supine. In both patients, angiography demonstrated arterial injury necessitating repair. Covered stent grafts were deployed through femoral cutdowns to exclude the areas of injury. In three additional patients, postoperative computed tomography imaging demonstrated pedicle screws abutting/penetrating the thoracic or abdominal aorta. Angiography or intravascular ultrasound imaging, or both, confirmed indention/perforation of the aorta by the screw. Aortic stent graft cuffs were deployed through femoral cutdowns to cover the area of aortic contact before hardware removal. All five patients did well and were discharged home in good condition. Endovascular repair of arterial injuries occurring during posterior spinal procedures is feasible and can offer a safe and less invasive alternative to open repair.

  12. 2013 ESH/ESC guidelines for the management of arterial hypertension: what has changed in daily clinical practice?

    PubMed

    Liakos, Charalampos I; Grassos, Charalampos A; Babalis, Dimitrios K

    2015-03-01

    This is a review article aiming to make focus on the changes made in the European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines for the management of arterial hypertension with some criticism for each element discussed in the text. Given that in the real world clinical practice physicians would hardly spend the time needed for studying the 77 pages manuscript of the recently released 2013 ESH/ESC hypertension guidelines, the present review summarizes all the significant updates (along with their clinical implications) compared to the 2007 ESH/ESC hypertension guidelines and the 2009 reappraisal document.

  13. Right Ventricular Myocardial Stiffness in Experimental Pulmonary Arterial Hypertension

    PubMed Central

    Rain, Silvia; Andersen, Stine; Najafi, Aref; Gammelgaard Schultz, Jacob; da Silva Gonçalves Bós, Denielli; Handoko, M. Louis; Bogaard, Harm-Jan; Vonk-Noordegraaf, Anton; Andersen, Asger; van der Velden, Jolanda; Ottenheijm, Coen A.C.

    2016-01-01

    Background— The purpose of this study was to determine the relative contribution of fibrosis-mediated and myofibril-mediated stiffness in rats with mild and severe right ventricular (RV) dysfunction. Methods and Results— By performing pulmonary artery banding of different diameters for 7 weeks, mild RV dysfunction (Ø=0.6 mm) and severe RV dysfunction (Ø=0.5 mm) were induced in rats. The relative contribution of fibrosis- and myofibril-mediated RV stiffness was determined in RV trabecular strips. Total myocardial stiffness was increased in trabeculae from both mild and severe RV dysfunction in comparison to controls. In severe RV dysfunction, increased RV myocardial stiffness was explained by both increased fibrosis-mediated stiffness and increased myofibril-mediated stiffness, whereas in mild RV dysfunction, only myofibril-mediated stiffness was increased in comparison to control. Histological analyses revealed that RV fibrosis gradually increased with severity of RV dysfunction, whereas the ratio of collagen I/III expression was only elevated in severe RV dysfunction. Stiffness measurements in single membrane-permeabilized RV cardiomyocytes demonstrated a gradual increase in RV myofibril stiffness, which was partially restored by protein kinase A in both mild and severe RV dysfunction. Increased expression of compliant titin isoforms was observed only in mild RV dysfunction, whereas titin phosphorylation was reduced in both mild and severe RV dysfunction. Conclusions— RV myocardial stiffness is increased in rats with mild and severe RV dysfunction. In mild RV dysfunction, stiffness is mainly determined by increased myofibril stiffness. In severe RV dysfunction, both myofibril- and fibrosis-mediated stiffness contribute to increased RV myocardial stiffness. PMID:27370069

  14. Macitentan treatment retards the progression of established pulmonary arterial hypertension in an animal model☆

    PubMed Central

    Temple, I.P.; Monfredi, O.; Quigley, G.; Schneider, H.; Zi, M.; Cartwright, E.J.; Boyett, M.R.; Mahadevan, V.S.; Hart, G.

    2014-01-01

    Background Macitentan is a new endothelin receptor antagonist that is used to treat pulmonary arterial hypertension in humans. Treatment of established pulmonary hypertension with macitentan was studied using the monocrotaline model of pulmonary hypertension. Methods Three groups of rats were created (n = 12): control (CON: macitentan only), monocrotaline (MCT: monocrotaline only) and macitentan (MACI: macitentan and monocrotaline). Monocrotaline (60 mg/kg) was injected in the MCT and MACI groups on day 0; volume matched saline was injected in the CON groups. Macitentan therapy (30 mg/kg/day) was commenced on day 11 in the CON and MACI groups. Serial echocardiography and ECGs were performed. The rats were sacrificed if they showed clinical deterioration. Results The MCT and MACI rats showed signs of pulmonary hypertension by day 7 (maximum pulmonary velocity, CON 1.15 ± 0.15 m/s vs MCT 1.04 ± 0.10 m/s vs MACI 0.99 ± 0.18 m/s; p < 0.05). Both the MCT and MACI groups developed pulmonary hypertension, but this was less severe in the MACI group (day 21 pulmonary artery acceleration time, MCT 17.55 ± 1.56 ms vs MACI 22.55 ± 1.00 ms; pulmonary artery deceleration, MCT 34.72 ± 3.72 m/s2 vs MACI 17.30 ± 1.89 m/s2; p < 0.05). Right ventricular hypertrophy and QT interval increases were more pronounced in MCT than MACI (right ventricle wall thickness, MCT 0.13 ± 0.1 cm vs MACI 0.10 ± 0.1 cm; QT interval, MCT 85 ± 13 ms vs MACI 71 ± 14 ms; p < 0.05). Survival benefit was not seen in the MACI group (p = 0.50). Conclusions Macitentan treatment improves haemodynamic parameters in established pulmonary hypertension. Further research is required to see if earlier introduction of macitentan has greater effects. PMID:25305681

  15. [Population models in the study of neurogenic domnants of arterial hypertension. Report 2. The peculiarities of arterial hypertension matched with personal motivational priorities].

    PubMed

    Tret'iakov, A Iu; Zakharchenko, S P; Shilenok, V N; Alferov, S P

    2007-01-01

    The peculiarities of primary arterial hypertension in persons with opposite types of motivational priorities were studied. The features and prevalence of the disease in two populations were analyzed. Group 1 consisted of 141 subjects whose profession and working conditions required maximum realization of the market-oriented motivational dominant ("socially active persons"); Group 2 consisted of 147 "altruistic" type subjects who lacked the first group's motivational dominant. The study found a higher prevalence of the disease and a lower level of psychological health as part of quality of life in Group 1 (p = 0.018); the disease in this group was more intensive and significant structural and functional left ventricular transformation was typical. The absence of pernicious habits and healthy life-style should not be considered primary factors of a more favorable clinical course of the disease in the "altruistic" group.

  16. Mechanisms of remodelling of small arteries, antihypertensive therapy and the immune system in hypertension.

    PubMed

    Schiffrin, Ernesto L

    2015-12-04

    This review summarizes my lecture for the 2015 Distinguished Scientist Award from the Canadian Society of Clinical Investigation, and is based mainly on studies in my laboratory on the mechanisms of remodelling of small arteries in experimental animal and human hypertension and on treatments that lower blood pressure and improve structure and function of resistance vessels. Small resistance arteries undergo either inward eutrophic or hypertrophic remodelling, which raises blood pressure and impairs tissue perfusion. These vascular changes are corrected by some antihypertensive drugs, which may lead to improved outcomes. Vasoconstriction, growth, oxidative stress and inflammation are some of the mechanisms, within the vascular wall, that can be beneficially affected by antihypertensive agents. These antihypertensive-sensitive mechanisms are reviewed in this review, together with the inflammatory and immune mechanisms that may participate in hypertension and associated cardiovascular injury. Molecular studies, based on this research, will hopefully identify novel diagnostic and therapeutic targets, which will improve our ability to prevent and treat hypertension and cardiovascular disease.

  17. Future Treatment of Hypertension: Shifting the Focus from Blood Pressure Lowering to Arterial Stiffness Modulation?

    PubMed

    Fok, Henry; Cruickshank, J Kennedy

    2015-08-01

    Isolated systolic hypertension is the commonest form of hypertension from middle age onwards. Achieving target systolic blood pressure (BP) control remains difficult in everyday clinical practice and even under clinical trial conditions. Most antihypertensive medicines were designed to lower peripheral vascular resistance, which was considered the haemodynamic determinant of hypertension; most are effective in reducing steady but not pulsatile components of BP. Arterial stiffness, defined via aortic length-specific pulse wave velocity (PWV), is thought to be an important determinant of pulse pressure widening through its effects on the timing and amplitude of pressure wave reflection, and/or the aorta's Windkessel function, or its excess 'reservoir' pressure. Whereas pulse pressure is neither an independent nor consistent cardiovascular risk factor, particularly below the age of about 60 years, PWV has become the most powerful predictor of cardiovascular outcomes including mortality, independent of systolic, pulse, mean or other BP components. PWV is therefore a more direct target for treatment. This review addresses the potential therapeutic options for targeting arterial stiffness and the role of pulse pressure.

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

    PubMed

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

    2015-01-01

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

  19. Control of intraoperative hypertension with isoflurane in patients with coronary artery disease: effects on regional myocardial blood flow and metabolism.

    PubMed

    Sahlman, L; Milocco, I; Appelgren, L; William-Olsson, G; Ricksten, S E

    1989-02-01

    The effect of isoflurane on regional myocardial metabolism and blood flow, when used as an adjunct to fentanyl-nitrous oxide anesthesia, to control intraoperative hypertension was investigated. Twenty-two patients with two- or three-vessel coronary artery disease with an ejection fraction greater than 0.5 and on beta-blockers up to the morning of surgery were studied during elective coronary artery by-pass grafting. Systemic and pulmonary hemodynamics, and regional (great cardiac vein, GCVF) myocardial blood flow and myocardial metabolic parameters were measured. In 10 patients, both GCVF and global (coronary sinus, CSF) myocardial blood flows were recorded. Measurements were made 1) after induction of anesthesia but prior to skin incision, 2) during sternotomy, and 3) during isoflurane administration after its use to reduce arterial pressure to the presternotomy level. The increase in systemic arterial pressure during sternotomy was due to an increase in systemic vascular resistance accompanied by increases in heart rate, pulmonary capillary wedge pressure, (PCWP) regional myocardial oxygen consumption and extraction, GCVF and total coronary vascular resistance. Isoflurane reduced systemic arterial pressure but not PCWP, to presternotomy levels within 6.9 +/- 0.7 minutes at an end-tidal concentration of 1.5 +/- 0.2%. Isoflurane induced a pronounced systemic and coronary vasodilatation and increases in cardiac index, heart rate and regional myocardial oxygen extraction while the GCVF/CSF ratio remained unchanged. While mean regional--MLE% values were not effected by sternotomy, in two patients myocardial lactate production was seen during sternotomy but not during isoflurane. In another two patients, isoflurane induced lactate production.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2783640

  20. Portal Hypertension and Ascites Due to an Arterioportal Fistula: Sequela of a Remote Traumatic Liver Laceration

    PubMed Central

    Hulkower, Benjamin M.; Butty, Sabah

    2016-01-01

    Arterioportal fistulas (APFs) are a group of vascular disorders, in which systemic arteries communicate with the portal circulation, presenting as a congenital syndrome or more commonly acquired from iatrogenic instrumentation or abdominal trauma. We report the case of a 58-year-old man who developed ascites without underlying risk factors for portal hypertension, which was attributed to an APF found on imaging, manifesting 43 years after sustaining a liver laceration. After angiographic embolization of the APF, the patient’s ascites resolved completely. The prolonged latent period between the patient’s abdominal trauma and eventual presentation with ascites highlights the need to consider vascular malformations in the differential diagnosis of unexplained noncirrhotic portal hypertension.

  1. 4-Phenylbutyric Acid Induces Protection against Pulmonary Arterial Hypertension in Rats

    PubMed Central

    Long, Mei; Wang, Jie; Liu, Fen; Gai, Min-Tao; Aierken, Alidan; Li, Ming-Yuan; Li, Qian; Wu, Lei-Qi; Ma, Yi-Tong; Hujiaaihemaiti, Minawaer

    2016-01-01

    Background Endoplasmic reticulum (ER) stress has been implicated in the pathophysiology of various pulmonary diseases via the activation of the unfolded protein response. However, the role of ER stress in pulmonary arterial hypertension (PAH) remains unclear. The well-known chemical chaperone 4-phenylbutyric acid (4-PBA) inhibits ER stress signaling. We hypothesized that known chemical chaperones, including 4-PBA, would inhibit the activation of ER stress and prevent and/or reverse PAH. Methods and Results Male Wistar rats were randomly divided into four groups: a normal control group (NORMAL group), a PAH group, and two PAH model plus 4-PBA treatment groups. The latter two groups included rats receiving 4-PBA by gavage each day as a preventive measure (the PRE group, with PBA starting on the day of PAH induction and continuing for 4 weeks) or as a reversal measure (the REV group, with PBA starting on the third week of PAH induction and continuing for 2 weeks). The PAH model was induced by intraperitoneally administering monocrotaline. The mean pulmonary artery pressure and mean right ventricular pressure were lower in the REV and PRE groups than in the NORMAL group. Furthermore, 4-PBA improved pulmonary arterial remodeling and suppressed the expression of ER stress indicators. Conclusion Our findings indicate that PAH induces ER stress and provokes pulmonary arterial and right ventricular remodeling. Additionally, we show that attenuation of ER stress has the potential to be an effective therapeutic strategy for protecting pulmonary arteries. PMID:27304885

  2. Pulmonary stenosis development and reduction of pulmonary arterial hypertension in atrioventricular septal defect: a case report

    PubMed Central

    Barth, Emeline; Bouvaist, Hélène; Marlière, Stéphanie; Ninet, Gérard; Vanzetto, Gérald

    2009-01-01

    A 24-year-old patient was admitted for dyspnoea and syncope. He had a previous history of complete atrio-ventricular septal defect and trisomy 21. At the age of 6 months, in 1984, cardiac catheterization revealed a quasi-systemic pulmonary arterial hypertension with a bidirectional shunt corresponding to an Eisenmenger syndrome. Corrective cardiac surgery was not performed at this time because surgical risk was considered too high. Until the age of 20 years old, he showed few symptoms while under medical treatment. But since 2006, his functional status became worse with an increased dyspnoea, syncopes, and severe cyanosis. In these conditions, haemodynamic parameters have been re-evaluated in 2006 and 2008. They highlighted a late and progressive development of a valvular and infundibular pulmonary stenosis leading to a normalisation of pulmonary arterial pressures. At the age of 24 , the patient underwent corrective cardiac surgery which was successful. Late development of both infundibular and valvular pulmonary stenosis have not been described before in non operated congenital ventricular septal defects, but development of one or the other abnormality would be found in 8% of patients. The physiopathological mechanism of this obstruction is unclear. Nevertheless, in unoperated congenital cardiac shunt lesions, reversibility of severe pulmonary arterial hypertension should be reconidered and re-assessed during follow up. PMID:19758423

  3. Calorie Restriction Attenuates Monocrotaline-induced Pulmonary Arterial Hypertension in Rats.

    PubMed

    Ding, Mingge; Lei, Jingyi; Qu, Yinxian; Zhang, Huan; Xin, Weichuan; Ma, Feng; Liu, Shuwen; Li, Zhichao; Jin, Faguang; Fu, Enqing

    2015-06-01

    Calorie restriction (CR) is one of the most effective nonpharmacological interventions protecting against cardiovascular disease, such as hypertension in the systemic circulation. However, whether CR could attenuate pulmonary arterial hypertension (PAH) is largely unknown. The PAH model was developed by subjecting the rats to a single subcutaneous injection of monocrotaline. CR lowered mean pulmonary arterial pressure (mPAP) and reduced vascular remodeling and right ventricular hypertrophy in PAH rats. Meanwhile, CR attenuated endothelial dysfunction as evidenced by increased relaxation in response to acetylcholine. The beneficial effects of CR were associated with restored sirtuin-1 (SIRT1) expression and endothelial nitric oxide synthase (eNOS) phosphorylation and reduced eNOS acetylation in pulmonary arteries of PAH rats. To further clarify the role of SIRT1 in the protective effects of CR, adenoviral vectors for overexpression of SIRT1 were administered intratracheally at 1 day before monocrotaline injection. Overexpression of SIRT1 exhibited similar beneficial effects on mPAP and endothelial function, and increased eNOS phosphorylation and reduced eNOS acetylation in the absence of CR. Moreover, SIRT1 overexpression attenuated the increase in mPAP in hypoxia-induced PAH animals. Overall, the present data demonstrate that CR may serve as an effective treatment of PAH, and targeting the SIRT1/eNOS pathway may improve treatment of PAH. PMID:25636073

  4. Left hemibody myoclonus due to anomalous right vertebral artery.

    PubMed

    Coelho, Miguel; Marti, Maria J; Valls-Solé, Josep; Pujol, Teresa; Tolosa, Eduardo

    2005-01-01

    A 43-year-old man presented with sporadic, sudden, brief, and involuntary jerks of his left limbs and trunk muscles. The electromyographic recordings showed short-lasting highly synchronized bursts, compatible with myoclonus limited to the left hemibody. Blink reflex, masseter silent period, cortical and spinal magnetic stimulation, somatosensory cortical evoked potentials, and electroencephalogram (EEG) were normal; the EEG back-averaging showed no spikes preceding the myoclonus. Magnetic resonance imaging and magnetic resonance angiography showed the presence of an anomalous nonectasic right vertebral artery compressing the right side of ventral medulla oblongata. We hypothesize that the aberrant right vertebral artery induced abnormal activation of descending motor tracts responsible for the myoclonus.

  5. Interleukin 13- and interleukin 17A-induced pulmonary hypertension phenotype due to inhalation of antigen and fine particles from air pollution.

    PubMed

    Park, Sung-Hyun; Chen, Wen-Chi; Esmaeil, Nafiseh; Lucas, Benjamin; Marsh, Leigh M; Reibman, Joan; Grunig, Gabriele

    2014-12-01

    Pulmonary hypertension has a marked detrimental effect on quality of life and life expectancy. In a mouse model of antigen-induced pulmonary arterial remodeling, we have recently shown that coexposure to urban ambient particulate matter (PM) significantly increased the thickening of the pulmonary arteries and also resulted in significantly increased right ventricular systolic pressures. Here we interrogate the mechanism and show that combined neutralization of interleukin 13 (IL-13) and IL-17A significantly ameliorated the increase in right ventricular systolic pressure, the circumferential muscularization of pulmonary arteries, and the molecular change in the right ventricle. Surprisingly, our data revealed a protective role of IL-17A for the antigen- and PM-induced severe thickening of pulmonary arteries. This protection was due to the inhibition of the effects of IL-13, which drove this response, and the expression of metalloelastase and resistin-like molecule α. However, the latter was redundant for the arterial thickening response. Anti-IL-13 exacerbated airway neutrophilia, which was due to a resulting excess effect of IL-17A, confirming concurrent cross inhibition of IL-13- and IL-17A-dependent responses in the lungs of animals exposed to antigen and PM. Our experiments also identified IL-13/IL-17A-independent molecular reprogramming in the lungs induced by exposure to antigen and PM, which indicates a risk for arterial remodeling and protection from arterial constriction. Our study points to IL-13- and IL-17A-coinduced inflammation as a new template for biomarkers and therapeutic targeting for the management of immune response-induced pulmonary hypertension. PMID:25610601

  6. Interleukin 13- and interleukin 17A-induced pulmonary hypertension phenotype due to inhalation of antigen and fine particles from air pollution.

    PubMed

    Park, Sung-Hyun; Chen, Wen-Chi; Esmaeil, Nafiseh; Lucas, Benjamin; Marsh, Leigh M; Reibman, Joan; Grunig, Gabriele

    2014-12-01

    Pulmonary hypertension has a marked detrimental effect on quality of life and life expectancy. In a mouse model of antigen-induced pulmonary arterial remodeling, we have recently shown that coexposure to urban ambient particulate matter (PM) significantly increased the thickening of the pulmonary arteries and also resulted in significantly increased right ventricular systolic pressures. Here we interrogate the mechanism and show that combined neutralization of interleukin 13 (IL-13) and IL-17A significantly ameliorated the increase in right ventricular systolic pressure, the circumferential muscularization of pulmonary arteries, and the molecular change in the right ventricle. Surprisingly, our data revealed a protective role of IL-17A for the antigen- and PM-induced severe thickening of pulmonary arteries. This protection was due to the inhibition of the effects of IL-13, which drove this response, and the expression of metalloelastase and resistin-like molecule α. However, the latter was redundant for the arterial thickening response. Anti-IL-13 exacerbated airway neutrophilia, which was due to a resulting excess effect of IL-17A, confirming concurrent cross inhibition of IL-13- and IL-17A-dependent responses in the lungs of animals exposed to antigen and PM. Our experiments also identified IL-13/IL-17A-independent molecular reprogramming in the lungs induced by exposure to antigen and PM, which indicates a risk for arterial remodeling and protection from arterial constriction. Our study points to IL-13- and IL-17A-coinduced inflammation as a new template for biomarkers and therapeutic targeting for the management of immune response-induced pulmonary hypertension.

  7. Interleukin 13– and interleukin 17A–induced pulmonary hypertension phenotype due to inhalation of antigen and fine particles from air pollution

    PubMed Central

    Park, Sung-Hyun; Chen, Wen-Chi; Esmaeil, Nafiseh; Lucas, Benjamin; Marsh, Leigh M.; Reibman, Joan

    2014-01-01

    Abstract Pulmonary hypertension has a marked detrimental effect on quality of life and life expectancy. In a mouse model of antigen-induced pulmonary arterial remodeling, we have recently shown that coexposure to urban ambient particulate matter (PM) significantly increased the thickening of the pulmonary arteries and also resulted in significantly increased right ventricular systolic pressures. Here we interrogate the mechanism and show that combined neutralization of interleukin 13 (IL-13) and IL-17A significantly ameliorated the increase in right ventricular systolic pressure, the circumferential muscularization of pulmonary arteries, and the molecular change in the right ventricle. Surprisingly, our data revealed a protective role of IL-17A for the antigen- and PM-induced severe thickening of pulmonary arteries. This protection was due to the inhibition of the effects of IL-13, which drove this response, and the expression of metalloelastase and resistin-like molecule α. However, the latter was redundant for the arterial thickening response. Anti-IL-13 exacerbated airway neutrophilia, which was due to a resulting excess effect of IL-17A, confirming concurrent cross inhibition of IL-13- and IL-17A-dependent responses in the lungs of animals exposed to antigen and PM. Our experiments also identified IL-13/IL-17A-independent molecular reprogramming in the lungs induced by exposure to antigen and PM, which indicates a risk for arterial remodeling and protection from arterial constriction. Our study points to IL-13- and IL-17A-coinduced inflammation as a new template for biomarkers and therapeutic targeting for the management of immune response–induced pulmonary hypertension. PMID:25610601

  8. Novel signaling pathways in pulmonary arterial hypertension (2015 Grover Conference Series).

    PubMed

    Awad, Keytam S; West, James D; de Jesus Perez, Vinicio; MacLean, Margaret

    2016-09-01

    The proliferative endothelial and smooth muscle cell phenotype, inflammation, and pulmonary vascular remodeling are prominent features of pulmonary arterial hypertension (PAH). Mutations in bone morphogenetic protein type 2 receptor (BMPR2) have been identified as the most common genetic cause of PAH and females with BMPR2 mutations are 2.5 times as likely to develop heritable forms of PAH than males. Higher levels of estrogen have also been observed in males with PAH, implicating sex hormones in PAH pathogenesis. Recently, the estrogen metabolite 16α-OHE1 (hydroxyestrone) was implicated in the regulation of miR29, a microRNA involved in modulating energy metabolism. In females, decreased miR96 enhances serotonin's effect by upregulating the 5-hydroxytryptamine 1B (5HT1B) receptor. Because PAH is characterized as a quasi-malignant disease, likely due to BMPR2 loss of function, altered signaling pathways that sustain this cancer-like phenotype are being explored. Extracellular signal-regulated kinases 1 and 2 and p38 mitogen-activated protein kinases (MAPKs) play a critical role in proliferation and cell motility, and dysregulated MAPK signaling is observed in various experimental models of PAH. Wnt signaling pathways preserve pulmonary vascular homeostasis, and dysregulation of this pathway could contribute to limited vascular regeneration in response to injury. In this review, we take a closer look at sex, sex hormones, and the interplay between sex hormones and microRNA regulation. We also focus on MAPK and Wnt signaling pathways in the emergence of a proproliferative, antiapoptotic endothelial phenotype, which then orchestrates an angioproliferative process of vascular remodeling, with the hope of developing novel therapies that could reverse the phenotype. PMID:27683605

  9. Novel signaling pathways in pulmonary arterial hypertension (2015 Grover Conference Series).

    PubMed

    Awad, Keytam S; West, James D; de Jesus Perez, Vinicio; MacLean, Margaret

    2016-09-01

    The proliferative endothelial and smooth muscle cell phenotype, inflammation, and pulmonary vascular remodeling are prominent features of pulmonary arterial hypertension (PAH). Mutations in bone morphogenetic protein type 2 receptor (BMPR2) have been identified as the most common genetic cause of PAH and females with BMPR2 mutations are 2.5 times as likely to develop heritable forms of PAH than males. Higher levels of estrogen have also been observed in males with PAH, implicating sex hormones in PAH pathogenesis. Recently, the estrogen metabolite 16α-OHE1 (hydroxyestrone) was implicated in the regulation of miR29, a microRNA involved in modulating energy metabolism. In females, decreased miR96 enhances serotonin's effect by upregulating the 5-hydroxytryptamine 1B (5HT1B) receptor. Because PAH is characterized as a quasi-malignant disease, likely due to BMPR2 loss of function, altered signaling pathways that sustain this cancer-like phenotype are being explored. Extracellular signal-regulated kinases 1 and 2 and p38 mitogen-activated protein kinases (MAPKs) play a critical role in proliferation and cell motility, and dysregulated MAPK signaling is observed in various experimental models of PAH. Wnt signaling pathways preserve pulmonary vascular homeostasis, and dysregulation of this pathway could contribute to limited vascular regeneration in response to injury. In this review, we take a closer look at sex, sex hormones, and the interplay between sex hormones and microRNA regulation. We also focus on MAPK and Wnt signaling pathways in the emergence of a proproliferative, antiapoptotic endothelial phenotype, which then orchestrates an angioproliferative process of vascular remodeling, with the hope of developing novel therapies that could reverse the phenotype.

  10. Protein Changes Contributing to Right Ventricular Cardiomyocyte Diastolic Dysfunction in Pulmonary Arterial Hypertension

    PubMed Central

    Rain, Silvia; Bos, Denielli da Silva Goncalves; Handoko, M. Louis; Westerhof, Nico; Stienen, Ger; Ottenheijm, Coen; Goebel, Max; Dorfmüller, Peter; Guignabert, Christophe; Humbert, Marc; Bogaard, Harm‐Jan; dos Remedios, Cris; Saripalli, Chandra; Hidalgo, Carlos G.; Granzier, Henk L.; Vonk‐Noordegraaf, Anton; van der Velden, Jolanda; de Man, Frances S.

    2014-01-01

    Background Right ventricular (RV) diastolic function is impaired in patients with pulmonary arterial hypertension (PAH). Our previous study showed that elevated cardiomyocyte stiffness and myofilament Ca2+ sensitivity underlie diastolic dysfunction in PAH. This study investigates protein modifications contributing to cellular diastolic dysfunction in PAH. Methods and Results RV samples from PAH patients undergoing heart‐lung transplantation were compared to non‐failing donors (Don). Titin stiffness contribution to RV diastolic dysfunction was determined by Western‐blot analyses using antibodies to protein‐kinase‐A (PKA), Cα (PKCα) and Ca2+/calmoduling‐dependent‐kinase (CamKIIδ) titin and phospholamban (PLN) phosphorylation sites: N2B (Ser469), PEVK (Ser170 and Ser26), and PLN (Thr17), respectively. PKA and PKCα sites were significantly less phosphorylated in PAH compared with donors (P<0.0001). To test the functional relevance of PKA‐, PKCα‐, and CamKIIδ‐mediated titin phosphorylation, we measured the stiffness of single RV cardiomyocytes before and after kinase incubation. PKA significantly decreased PAH RV cardiomyocyte diastolic stiffness, PKCα further increased stiffness while CamKIIδ had no major effect. CamKIIδ activation was determined indirectly by measuring PLN Thr17phosphorylation level. No significant changes were found between the groups. Myofilament Ca2+ sensitivity is mediated by sarcomeric troponin I (cTnI) phosphorylation. We observed increased unphosphorylated cTnI in PAH compared with donors (P<0.05) and reduced PKA‐mediated cTnI phosphorylation (Ser22/23) (P<0.001). Finally, alterations in Ca2+‐handling proteins contribute to RV diastolic dysfunction due to insufficient diastolic Ca2+ clearance. PAH SERCA2a levels and PLN phosphorylation were significantly reduced compared with donors (P<0.05). Conclusions Increased titin stiffness, reduced cTnI phosphorylation, and altered levels of phosphorylation of Ca2

  11. Novel signaling pathways in pulmonary arterial hypertension (2015 Grover Conference Series)

    PubMed Central

    West, James D.; de Jesus Perez, Vinicio; MacLean, Margaret

    2016-01-01

    Abstract The proliferative endothelial and smooth muscle cell phenotype, inflammation, and pulmonary vascular remodeling are prominent features of pulmonary arterial hypertension (PAH). Mutations in bone morphogenetic protein type 2 receptor (BMPR2) have been identified as the most common genetic cause of PAH and females with BMPR2 mutations are 2.5 times as likely to develop heritable forms of PAH than males. Higher levels of estrogen have also been observed in males with PAH, implicating sex hormones in PAH pathogenesis. Recently, the estrogen metabolite 16α-OHE1 (hydroxyestrone) was implicated in the regulation of miR29, a microRNA involved in modulating energy metabolism. In females, decreased miR96 enhances serotonin’s effect by upregulating the 5-hydroxytryptamine 1B (5HT1B) receptor. Because PAH is characterized as a quasi-malignant disease, likely due to BMPR2 loss of function, altered signaling pathways that sustain this cancer-like phenotype are being explored. Extracellular signal–regulated kinases 1 and 2 and p38 mitogen-activated protein kinases (MAPKs) play a critical role in proliferation and cell motility, and dysregulated MAPK signaling is observed in various experimental models of PAH. Wnt signaling pathways preserve pulmonary vascular homeostasis, and dysregulation of this pathway could contribute to limited vascular regeneration in response to injury. In this review, we take a closer look at sex, sex hormones, and the interplay between sex hormones and microRNA regulation. We also focus on MAPK and Wnt signaling pathways in the emergence of a proproliferative, antiapoptotic endothelial phenotype, which then orchestrates an angioproliferative process of vascular remodeling, with the hope of developing novel therapies that could reverse the phenotype. PMID:27683605

  12. Novel signaling pathways in pulmonary arterial hypertension (2015 Grover Conference Series)

    PubMed Central

    West, James D.; de Jesus Perez, Vinicio; MacLean, Margaret

    2016-01-01

    Abstract The proliferative endothelial and smooth muscle cell phenotype, inflammation, and pulmonary vascular remodeling are prominent features of pulmonary arterial hypertension (PAH). Mutations in bone morphogenetic protein type 2 receptor (BMPR2) have been identified as the most common genetic cause of PAH and females with BMPR2 mutations are 2.5 times as likely to develop heritable forms of PAH than males. Higher levels of estrogen have also been observed in males with PAH, implicating sex hormones in PAH pathogenesis. Recently, the estrogen metabolite 16α-OHE1 (hydroxyestrone) was implicated in the regulation of miR29, a microRNA involved in modulating energy metabolism. In females, decreased miR96 enhances serotonin’s effect by upregulating the 5-hydroxytryptamine 1B (5HT1B) receptor. Because PAH is characterized as a quasi-malignant disease, likely due to BMPR2 loss of function, altered signaling pathways that sustain this cancer-like phenotype are being explored. Extracellular signal–regulated kinases 1 and 2 and p38 mitogen-activated protein kinases (MAPKs) play a critical role in proliferation and cell motility, and dysregulated MAPK signaling is observed in various experimental models of PAH. Wnt signaling pathways preserve pulmonary vascular homeostasis, and dysregulation of this pathway could contribute to limited vascular regeneration in response to injury. In this review, we take a closer look at sex, sex hormones, and the interplay between sex hormones and microRNA regulation. We also focus on MAPK and Wnt signaling pathways in the emergence of a proproliferative, antiapoptotic endothelial phenotype, which then orchestrates an angioproliferative process of vascular remodeling, with the hope of developing novel therapies that could reverse the phenotype.

  13. Renal artery denervation for treating resistant hypertension : definition of the disease, patient selection and description of the procedure.

    PubMed

    Volpe, Massimo; Rosei, Enrico Agabiti; Ambrosioni, Ettore; Cottone, Santina; Cuspidi, Cesare; Borghi, Claudio; De Luca, Nicola; Fallo, Francesco; Ferri, Claudio; Mancia, Giuseppe; Morganti, Alberto; Muiesan, Maria Lorenza; Sarzani, Riccardo; Sechi, Leonardo; Tocci, Giuliano; Virdis, Agostino

    2012-12-01

    Arterial hypertension is responsible for a significant burden of cardiovascular morbidity and mortality, worldwide. Although several rational and integrated pharmacological strategies are available, the control of high blood pressure still remains largely unsatisfactory. Failure to achieve effective blood pressure control in treated hypertensive patients may have a substantial impact on individual global cardiovascular risk, since it significantly increases the risk of developing hypertension-related macrovascular and microvascular complications. Arterial hypertension is arbitrarily defined as 'resistant' or 'refractory' when the recommended blood pressure goals (clinic blood pressure below 140/90 mmHg or below 130/80 mmHg in patients with type 2 diabetes mellitus or nephropathy) are not achieved in the presence of a therapeutic strategy that includes lifestyle changes and at least three classes of antihypertensive drugs, including a diuretic, at adequate doses. Recently, an innovative non-pharmacological option has become available for treating resistant hypertension. Sympathetic denervation of renal arteries is a minimally invasive procedure that is performed via percutaneous access from the femoral artery. It consists of radiofrequency ablation of the afferent and efferent nerves of the renal sympathetic nervous system, with consequent isolation of renal parenchymal and juxtaglomerular structures from abnormal stimulation of the efferent adrenergic system. The present position paper of the Italian Society of Hypertension (SIIA) offers a diagnostic and therapeutic approach for the proper identification and effective clinical management of patients with resistant hypertension, who are candidates for renal artery denervation. These indications may have important implications not only from a clinical point of view, but also from an economic point of view, since a proper identification of patients with true resistant hypertension and an accurate selection of patients

  14. Combination therapy using PSE and TIO ameliorates hepatic encephalopathy due to intrahepatic portosystemic venous shunt in idiopathic portal hypertension

    PubMed Central

    Kojima, Seiichiro; Ito, Hiroyuki; Takashimizu, Shinji; Ichikawa, Hitoshi; Matsumoto, Tomohiro; Hasebe, Terumitsu

    2016-01-01

    A 64-year-old woman treated for anemia and ascites exhibited hepatic encephalopathy. Abdominal ultrasonography and computed tomography (CT) showed communication between the portal vein and the middle hepatic vein, indicating an intrahepatic portosystemic venous shunt (PSS). Since hepatic encephalopathy of the patient was resistant to medical treatment, interventional radiology was performed for the treatment of shunt obliteration. Hepatic venography showed anastomosis between the hepatic vein branches, supporting the diagnosis of idiopathic portal hypertension (IPH). To minimize the increase in portal vein pressure after shunt obliteration, partial splenic artery embolization (PSE) was first performed to reduce portal vein blood flow. Transileocolic venous obliteration (TIO) was then performed, and intrahepatic PSS was successfully obliterated using coils with n-butyl-2-cyanoacrylate (NBCA). In the present case, hepatic encephalopathy due to intrahepatic PSS in the patient with IPH was successfully treated by combination therapy using PSE and TIO.

  15. Combination therapy using PSE and TIO ameliorates hepatic encephalopathy due to intrahepatic portosystemic venous shunt in idiopathic portal hypertension.

    PubMed

    Kojima, Seiichiro; Ito, Hiroyuki; Takashimizu, Shinji; Ichikawa, Hitoshi; Matsumoto, Tomohiro; Hasebe, Terumitsu; Watanabe, Norihito

    2016-09-01

    A 64-year-old woman treated for anemia and ascites exhibited hepatic encephalopathy. Abdominal ultrasonography and computed tomography (CT) showed communication between the portal vein and the middle hepatic vein, indicating an intrahepatic portosystemic venous shunt (PSS). Since hepatic encephalopathy of the patient was resistant to medical treatment, interventional radiology was performed for the treatment of shunt obliteration. Hepatic venography showed anastomosis between the hepatic vein branches, supporting the diagnosis of idiopathic portal hypertension (IPH). To minimize the increase in portal vein pressure after shunt obliteration, partial splenic artery embolization (PSE) was first performed to reduce portal vein blood flow. Transileocolic venous obliteration (TIO) was then performed, and intrahepatic PSS was successfully obliterated using coils with n-butyl-2-cyanoacrylate (NBCA). In the present case, hepatic encephalopathy due to intrahepatic PSS in the patient with IPH was successfully treated by combination therapy using PSE and TIO. PMID:27651930

  16. Combination therapy using PSE and TIO ameliorates hepatic encephalopathy due to intrahepatic portosystemic venous shunt in idiopathic portal hypertension

    PubMed Central

    Kojima, Seiichiro; Ito, Hiroyuki; Takashimizu, Shinji; Ichikawa, Hitoshi; Matsumoto, Tomohiro; Hasebe, Terumitsu

    2016-01-01

    A 64-year-old woman treated for anemia and ascites exhibited hepatic encephalopathy. Abdominal ultrasonography and computed tomography (CT) showed communication between the portal vein and the middle hepatic vein, indicating an intrahepatic portosystemic venous shunt (PSS). Since hepatic encephalopathy of the patient was resistant to medical treatment, interventional radiology was performed for the treatment of shunt obliteration. Hepatic venography showed anastomosis between the hepatic vein branches, supporting the diagnosis of idiopathic portal hypertension (IPH). To minimize the increase in portal vein pressure after shunt obliteration, partial splenic artery embolization (PSE) was first performed to reduce portal vein blood flow. Transileocolic venous obliteration (TIO) was then performed, and intrahepatic PSS was successfully obliterated using coils with n-butyl-2-cyanoacrylate (NBCA). In the present case, hepatic encephalopathy due to intrahepatic PSS in the patient with IPH was successfully treated by combination therapy using PSE and TIO. PMID:27651930

  17. Chronic thromboembolic pulmonary arterial hypertension: a review of the literature and novel therapeutic approaches.

    PubMed

    Androulakis, Emmanuel; Lioudaki, Eirini; Christophides, Theodoros; Ahmad, Mahmood; Fayed, Hossam; Laskar, Nabila; Schreiber, Benjamin

    2015-06-01

    Chronic thromboembolic pulmonary hypertension is defined as pulmonary hypertension (PH) caused by single or recurrent pulmonary emboli and is characterized by chronic obstruction of the pulmonary arteries leading to increased vascular resistance and PH. Also, progressive remodeling may occur in occluded and nonoccluded territories. Better understanding of the underlying mechanisms and risk factors could improve diagnosis and allow appropriate interventions. Pulmonary endarterectomy is an established approach and is considered the definitive treatment for chronic PH, resulting from thromboembolic disease. Furthermore, percutaneous transluminal pulmonary angioplasty is technically feasible, especially for those with peripheral-type of the disease. In addition, several agents, including prostanoids, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors, have been tested in selected patients yielding promising results. Several novel agents are under investigation, and extensive research is currently in progress aiming to resolve uncertainties in the understanding and treatment of the disease.

  18. The thrill of success: central arterial-venous anastomosis for hypertension.

    PubMed

    Fudim, Marat; Stanton, Alice; Sobotka, Paul A; Dolan, Eamon; Krum, Henry

    2014-12-01

    Excess blood pressure remains the most important risk factor for cardiovascular and renal disease. Poly pharmacy has been proved safe and effective under clinical trial circumstances; however, the majority of patients fail to sustain pharmaceutical persistence and adherence. The opportunity to offer patients a treatment or device in addition or perhaps instead of drug therapy alone may significantly broaden the options for patients and allow greater success in hypertensive therapy. In this review, we examine the potential of a fixed-volume central arterial-venous anastomosis to reduce blood pressure in hypertensive patients, review possible mechanisms by which the anastomosis may reduce blood pressure, and consider the unique clinical trial opportunities posed by this therapy.

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

    PubMed

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

    2016-03-01

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

  20. ASCOT-LLA and the primary prevention of coronary artery disease in hypertensive patients.

    PubMed

    Nambi, Vijay; Ballantyne, Christie M

    2004-09-01

    Although each revision of the US National Cholesterol Education Program guidelines has made increasing provision for the use of global risk assessment in determining need for and intensity of therapy, the guidelines' continued focus on low-density lipoprotein (LDL) cholesterol may result in inadequate or no treatment for individuals at high risk for coronary artery disease (CAD) who do not have substantially elevated LDL cholesterol. However, recent clinical trial evidence has shown that high-risk patients benefit from lipid-regulating therapy regardless of LDL cholesterol level. In the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm, high-risk hypertensive patients had reductions in clinical events despite not having substantially elevated LDL cholesterol at baseline. These results suggest that all hypertensive patients with additional risk factors should receive lipid-regulating statin therapy to prevent CAD events.

  1. Linked opening angle and histological and mechanical aspects of the proximal pulmonary arteries of healthy and pulmonary hypertensive rats and calves.

    PubMed

    Tian, Lian; Lammers, Steven R; Kao, Philip H; Reusser, Mark; Stenmark, Kurt R; Hunter, Kendall S; Qi, H Jerry; Shandas, Robin

    2011-11-01

    Understanding how arterial remodeling changes the mechanical behavior of pulmonary arteries (PAs) is important to the evaluation of pulmonary vascular function. Early and current efforts have focused on the arteries' histological changes, their mechanical properties under in vitro mechanical testing, and their zero-stress and no-load states. However, the linkage between the histology and mechanical behavior is still not well understood. To explore this linkage, we investigated the geometry, residual stretch, and histology of proximal PAs in both adult rat and neonatal calf hypoxic models of pulmonary hypertension (PH), compared their changes due to chronic hypoxia across species, and proposed a two-layer mechanical model of artery to relate the opening angle to the stiffness ratio of the PA outer to inner layer. We found that the proximal PA remodeling in calves was quite different from that in rats. In rats, the arterial wall thickness, inner diameter, and outer layer thickness fraction all increased dramatically in PH and the opening angle decreased significantly, whereas in calves, only the arterial wall thickness increased in PH. The proposed model predicted that the stiffness ratio of the calf proximal PAs changed very little from control to hypertensive group, while the decrease of opening angle in rat proximal PAs in response to chronic hypoxia was approximately linear to the increase of the stiffness ratio. We conclude that the arterial remodeling in rat and calf proximal PAs is different and the change of opening angle can be linked to the change of the arterial histological structure and mechanics. PMID:21856906

  2. [Cerebellar infarction due to vertebral artery dissection in a girl].

    PubMed

    Ushida, M; Fukuda, K; Endo, S; Pu, T; Nakagawa, Y; Shiino, S; Otomune, T; Nakano, O

    1998-11-01

    We report here a case of vertebral artery dissection, which is rare in childhood. A 12-year-old, previous healthy girl was admitted to our hospital with symptoms of vertigo, tinnitus, hearing loss, nausea and vomiting. Although there was neither higher cortical dysfunction, motor weakness, sensory disturbance nor slurred speech. She could not stand up because of severe vertigo. Cranial magnetic resonance imaging (MRI) revealed a subacute cerebellar infarct. A left vertebral artery angiogram on the hospital day 3 demonstrated a sharp narrowing at the C1-C2 level. After an anticoagulant therapy for about 2 weeks, all the symptoms disappeared except for mild tinnitus. Two months later, a left vertebral artery angiogram showed an abrupt occlusion at the C1 level. MRI T1-weighted images demonstrated a thrombus within the false lumen of the dissected vessels. A flow void revealed the patency of the residual true lumen. From these findings, we made a diagnosis of vertebral artery dissection, which was considered to have caused cerebellar infarction. The patient was mostly normal at discharge, and 100 mg/day of aspirin has been given until present.

  3. Lipid X ameliorates pulmonary hypertension and protects sheep from death due to endotoxin.

    PubMed Central

    Golenbock, D T; Will, J A; Raetz, C R; Proctor, R A

    1987-01-01

    Lipid X (2,3-diacylglucosamine-1-phosphate) is a novel monosaccharide precursor of lipid A that has some of the physiologic activities of endotoxin but little toxicity. To determine whether lipid X would interfere with the toxic effects of endotoxin, we pretreated sheep with either 100 or 200 micrograms of lipid X per kg of body weight and then challenged them with a potentially fatal dose of Escherichia coli endotoxin (20 micrograms/kg). Twenty-one sheep underwent pulmonary artery catheterization and were monitored for changes in pulmonary artery pressure, temperature, pH, partial O2 pressure, partial CO2 pressure, blood pressure, and cell counts over 7 h. Overall mortality for control animals was 37% versus 5.3% for pretreated animals. None of the 13 animals pretreated with 100 micrograms of lipid X per kg died. These differences in survival were significant (P less than 0.05). Animals pretreated with 100 micrograms of lipid X per kg had significantly lower pulmonary artery pressure during both phases 1 and 2 of endotoxin-induced pulmonary artery hypertension. A higher dose of lipid X, 200 micrograms/kg, produced pulmonary hypertension. Perhaps because lipid X is a subunit of lipid A, lipid X shows a partial pyrogenic effect while also decreasing the pyrogenic activity of complete lipopolysaccharide (LPS). Lipid X did not prevent endotoxin-induced neutropenia or moderate hypotension in response to LPS. Lipid X is a potential prototype compound for a new type of chemotherapy directed at blocking the harmful effects of LPS during bacterial septicemia. PMID:3308707

  4. Cardiac Organ Damage and Arterial Stiffness in Autonomic Failure: Comparison With Essential Hypertension.

    PubMed

    Milazzo, Valeria; Maule, Simona; Di Stefano, Cristina; Tosello, Francesco; Totaro, Silvia; Veglio, Franco; Milan, Alberto

    2015-12-01

    Autonomic failure (AF) is characterized by orthostatic hypotension, supine hypertension, and increased blood pressure (BP) variability. AF patients develop cardiac organ damage, similarly to essential hypertension (EH), and have higher arterial stiffness than healthy controls. Determinants of cardiovascular organ damage in AF are not well known: both BP variability and mean BP values may be involved. The aim of the study was to evaluate cardiac organ damage, arterial stiffness, and central hemodynamics in AF, compared with EH subjects with similar 24-hour BP and a group of healthy controls, and to evaluate determinants of target organ damage in patients with AF. Twenty-seven patients with primary AF were studied (mean age, 65.7±11.2 years) using transthoracic echocardiography, carotid-femoral pulse wave velocity, central hemodynamics, and 24-hour ambulatory BP monitoring. They were compared with 27 EH subjects matched for age, sex, and 24-hour mean BP and with 27 healthy controls. AF and EH had similar left ventricular mass (101.6±33.3 versus 97.7±28.1 g/m(2), P=0.59) and carotid-femoral pulse wave velocity (9.3±1.8 versus 9.2±3.0 m/s, P=0.93); both parameters were significantly lower in healthy controls (P<0.01). Compared with EH, AF patients had higher augmentation index (31.0±7.6% versus 26.1±9.2%, P=0.04) and central BP values. Nighttime systolic BP and 24-hour systolic BP predicted organ damage, independent of BP variability. AF patients develop hypertensive heart disease and increased arterial stiffness, similar to EH with comparable mean BP values. Twenty-four-hour and nighttime systolic BP were determinants of cardiovascular damage, independent of BP variability.

  5. Riociguat for the treatment of pulmonary arterial hypertension: a long-term extension study (PATENT-2).

    PubMed

    Rubin, Lewis J; Galiè, Nazzareno; Grimminger, Friedrich; Grünig, Ekkehard; Humbert, Marc; Jing, Zhi-Cheng; Keogh, Anne; Langleben, David; Fritsch, Arno; Menezes, Flavia; Davie, Neil; Ghofrani, Hossein-Ardeschir

    2015-05-01

    Riociguat is a soluble, guanylate cyclase stimulator, approved for pulmonary arterial hypertension. In the 12-week PATENT-1 study, riociguat was well tolerated and improved several clinically relevant end-points in patients with pulmonary arterial hypertension who were treatment naïve or had been pretreated with endothelin-receptor antagonists or prostanoids. The PATENT-2 open-label extension evaluated the long-term safety and efficacy of riociguat. Eligible patients from the PATENT-1 study received riociguat individually adjusted up to a maximum dose of 2.5 mg three times daily. The primary objective was to assess the safety and tolerability of riociguat; exploratory efficacy assessments included 6-min walking distance and World Health Organization (WHO) functional class. Overall, 396 patients entered the PATENT-2 study and 324 (82%) were ongoing at this interim analysis (March 2013). The safety profile of riociguat in PATENT-2 was similar to that observed in PATENT-1, with cases of haemoptysis and pulmonary haemorrhage also being observed in PATENT-2. Improvements in the patients', 6-min walking distance and WHO functional class observed in PATENT-1 persisted for up to 1 year in PATENT-2. In the observed population at the 1-year time point, mean±sd 6-min walking distance had changed by 51±74 m and WHO functional class had improved in 33%, stabilised in 61% and worsened in 6% of the patients versus the PATENT-1 baseline. Long-term riociguat was well tolerated in patients with pulmonary arterial hypertension, and led to sustained improvements in exercise capacity and functional capacity for up to 1 year.

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

    PubMed

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

    2012-06-01

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

  7. Individual differences as predictors of dietary patterns among menopausal women with arterial hypertension

    PubMed Central

    2014-01-01

    Introduction The aim of this study was to analyze selected individual determinants of dietary choices, important for etiology and prevention of degenerative cardiovascular disorders, in a group of menopausal women diagnosed with arterial hypertension. Material and methods The study included a group of 160 women from the Małopolska region, aged between 45 and 60 years and diagnosed with arterial hypertension. A questionnaire assessing the frequency of food product consumption was used, along with standardized psychological tests (GSES, LOT-R, and SWLS). Spearman's coefficients of rank correlation and the Kruskal-Wallis and Dunn tests were used for statistical analysis. Results We revealed that higher levels of self-efficacy were associated with more frequent consumption of whole grains, oatmeal, raw vegetables, fruit, semi-skimmed milk, natural yoghurt, marine fish, legume seeds, soy products, nuts, plant oils, and fruit and vegetable juices, as well as with less frequent consumption of whole milk, high-fat cottage cheese, and sweetened carbonated beverages and alcoholic beverages. The levels of optimism and satisfaction with life correlated positively with the consumption frequency of brown rice, whole grains, oatmeal, fruit, marine fish, legumes, soy products, nuts, butter, and fruit juices, and were inversely correlated with the consumption of white bread, high-fat cottage cheese, pork meat and sausages, and sweets and pastries. Conclusions Postmenopausal women with arterial hypertension who were characterized by lower levels of self-efficacy, optimism, and satisfaction with life made less rational dietary choices which could negatively affect the efficacy of the secondary prevention of cardiovascular degenerative disorders. PMID:26327838

  8. Definition and classification of pulmonary hypertension.

    PubMed

    Humbert, Marc; Montani, David; Evgenov, Oleg V; Simonneau, Gérald

    2013-01-01

    Pulmonary hypertension is defined as an increase of mean pulmonary arterial pressure ≥25 mmHg at rest as assessed by right heart catheterization. According to different combinations of values of pulmonary wedge pressure, pulmonary vascular resistance and cardiac output, a hemodynamic classification of pulmonary hypertension has been proposed. Of major importance is the pulmonary wedge pressure which allows to distinguish pre-capillary (pulmonary wedge pressure ≤15 mmHg) and post-capillary (pulmonary wedge pressure >15 mmHg) pulmonary hypertension. Pre-capillary pulmonary hypertension includes the clinical groups 1 (pulmonary arterial hypertension), 3 (pulmonary hypertension due to lung diseases and/or hypoxia), 4 (chronic thrombo-embolic pulmonary hypertension) and 5 (pulmonary hypertension with unclear and/or multifactorial mechanisms). Post-capillary pulmonary hypertension corresponds to the clinical group 2 (pulmonary hypertension due to left heart diseases).

  9. Acute resynchronization with inhaled iloprost in a pregnant woman with idiopathic pulmonary artery hypertension.

    PubMed

    Cotrim, Carlos; Simões, Otília; Loureiro, M J; Cordeiro, Pedro; Miranda, Rita; Silva, Cecília; Avillez, Teresa; Carrageta, Manuel

    2006-05-01

    We describe the case of a pregnant woman with idiopathic pulmonary arterial hypertension, a responder in right heart catheterization, followed since the first trimester in outpatient consultations, admitted to hospital at 23 weeks gestation. She was treated with inhaled iloprost until delivery (at 34 weeks gestation) and continuous infusion of iloprost throughout the perioperative period and following days. This line of therapy has proved efficacious in previous cases. The authors present echocardiographic images that document acute changes in ventricular synchrony during inhalation of iloprost.

  10. Exercise stress echocardiography for detection of pulmonary arterial hypertension in a patient with systemic sclerosis.

    PubMed

    Cotrim, Carlos; Cordeiro, Ana; Loureiro, Maria José; Santos, Maria José; Simões, Otília; Cordeiro, Pedro; da Silva, J Canas; Carrageta, Manuel

    2006-02-01

    The authors report the case of a 57-year-old patient, diagnosed with systemic sclerosis 16 years ago. She had been followed in the rheumatology outpatient clinic since 2003 and complained of marked fatigue and dyspnea on exertion. In addition to full medical evaluation, she also underwent standard Doppler echocardiography at rest, which was unremarkable, and exercise stress echocardiography. In the latter examination, she was diagnosed with pulmonary arterial hypertension, later confirmed during right heart catheterization. The authors discuss the potential value of this methodology for the study of patients with systemic sclerosis.

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

    PubMed

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

    2015-09-01

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

  12. Monitoring and Diagnostic Approaches for Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis.

    PubMed

    Valenzuela, Antonia; Nandagopal, Saranya; Steen, Virginia D; Chung, Lorinda

    2015-08-01

    Pulmonary arterial hypertension (PAH) is one of the leading causes of death in patients with systemic sclerosis (SSc). Given the high prevalence and poor survival of SSc-PAH, and that aggressive management of mild disease may be associated with better outcomes, screening is critical. Right heart catheterization (RHC) is the gold standard for the definitive diagnosis of PAH, and should be performed in those patients in whom this diagnosis is suspected. Once a diagnosis of PAH is confirmed by RHC, treatment with PAH-specific therapies should be initiated as soon as possible.

  13. [Rehabilitative medical technology for the correction of microcirculatory disorders in patients with arterial hypertension].

    PubMed

    Kul'chitskaia, D B

    2009-01-01

    The study with the use of laser Doppler flowmetry has revealed pathological changes in the microcirculatory system of patients with arterial hypertension. Their treatment with a low-frequency magnetic field showed that its effect on microcirculation depends on the regime and site of application of magnetotherapy as well as its combination with other physical factors. Frontal application of the magnetic field had the most pronounced beneficial effect on dynamic characteristics of microcirculation. Pulsed regime of magnetotherapy was more efficacious than conventional one. Amplipulse magnetotherapy produced better results than monotherapy. PMID:19886016

  14. Where do we go from here? Reappraising the data on anticoagulation in pulmonary arterial hypertension.

    PubMed

    Cirulis, Meghan M; Ryan, John J

    2016-05-01

    The use of anticoagulation as part of the treatment regimen in pulmonary arterial hypertension (PAH) remains a topic of debate. A recently published analysis of anticoagulation use in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) study offers conflicting conclusions regarding the benefit of this therapeutic strategy. There remains no robust randomized trial in PAH weighing the risks versus benefits of including anticoagulation in treatment regimens, leaving clinicians to surmise value in individual patients. Reexamination of available data may help to provide guidance on this controversial topic in the absence of future dedicated investigations. PMID:27162687

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

    PubMed Central

    2015-01-01

    Abstract Respiratory and limb muscle dysfunction is emerging as an important pathophysiological abnormality in pulmonary arterial hypertension (PAH). Muscle abnormalities appear to occur frequently and promote dyspnea, fatigue, and exercise limitation in patients with PAH. Preliminary data suggest that targeted muscle training may be of benefit, although further evidence is required to consolidate these findings into specific recommendations for exercise training in patients with PAH. This article reviews the current evidence on prevalence, risk factors, and implications of respiratory and limb muscle dysfunction in patients with PAH. It also reviews the impact of exercise rehabilitation on morphologic, metabolic, and functional muscle profile and outcomes in PAH. Future research priorities are highlighted. PMID:26401245

  16. Effects of calcium and potassium supplements on arterial tone in vitro in spontaneously hypertensive rats

    PubMed Central

    Tolvanen, Jari-Petteri; Mäkynen, Heikki; Wu, Xiumin; Hutri-Kähönen, Nina; Rsukoaho, Heikki; Karjala, Kirsi; Pörsti, Ilkka

    1998-01-01

    Calcium and potassium intakes inversely correlate with blood pressure in experimental hypertension. Therefore, we examined the effects of calcium and potassium supplements alone and in combination on arterial tone in spontaneously hypertensive rats (SHR). Wistar-Kyoto (WKY) rats served as normotensive controls. Calcium and potassium contents in the control diet were both 1%, while those in supplemented chows were 3% and 3.5%, respectively. The sodium content of all diets was moderately elevated to 1.1%.After 12 weeks of the study systolic blood pressures in SHR on high calcium and on high potassium diets were markedly lower (about 53 and 58 mmHg, respectively) than in hypertensive controls, while combined supplementation of these cations reduced blood pressure even further (about 69 mmHg).Responses of mesenteric arterial rings in vitro were examined at the end of the study. Both high calcium and high potassium diets improved the impaired relaxation to acetylcholine (ACh) in SHR, while the combination of these supplements completely normalized this response. Cyclo-oxygenase inhibition by diclofenac augmented the relaxation to ACh in hypertensive controls but not in the other groups. Nevertheless, enhanced endothelium-mediated dilatation was still observed in the presence of diclofenac and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in all supplemented groups. Interestingly, additional blockade of Ca2+-activated K+ channels by tetraethylammonium abolished the improved relaxation to ACh in SHR on high calcium and on high potassium, but distinct responses were still observed in WKY rats and SHR on the combined supplement.When hyperpolarization of smooth muscle was prevented by precontraction of the preparations with 50 mM KCl, only marginal differences were observed in the diclofenac and L-NAME-resistant relaxations to ACh between the study groups. Finally, endothelium-independent vasorelaxations of noradrenaline

  17. Bridge to thoracic organ transplantation in patients with pulmonary arterial hypertension using a pumpless lung assist device.

    PubMed

    Strueber, M; Hoeper, M M; Fischer, S; Cypel, M; Warnecke, G; Gottlieb, J; Pierre, A; Welte, T; Haverich, A; Simon, A R; Keshavjee, S

    2009-04-01

    We describe a novel technique of pumpless extracorporeal life support in four patients with cardiogenic shock due to end-stage pulmonary hypertension (PH) including patients with veno-occlusive disease (PVOD) using a pumpless lung assist device (LAD). The device was connected via the pulmonary arterial main trunk and the left atrium, thereby creating a septostomy-like shunt with the unique addition of gas exchange abilities in parallel to the lung. Using this approach, all four patients were successfully bridged to bilateral lung transplantation and combined heart-lung transplantation, respectively. Although all patients presented in cardiogenic shock, hemodynamic unloading of the right ventricle using the low-resistance LAD stabilized the hemodynamic situation immediately so that no pump support was subsequently required. PMID:19344471

  18. Joint statement of the European Association for the Study of Obesity and the European Society of Hypertension: obesity and difficult to treat arterial hypertension.

    PubMed

    Jordan, Jens; Yumuk, Volkan; Schlaich, Markus; Nilsson, Peter M; Zahorska-Markiewicz, Barbara; Grassi, Guido; Schmieder, Roland E; Engeli, Stefan; Finer, Nick

    2012-06-01

    Obese patients are prone to arterial hypertension, require more antihypertensive medications, and have an increased risk of treatment-resistant arterial hypertension. Obesity-induced neurohumoral activation appears to be involved. The association between obesity and hypertension shows large inter-individual variability, likely through genetic mechanisms. Obesity affects overall cardiovascular and metabolic risk; yet, the relationship between obesity and cardiovascular risk is complex and not sufficiently addressed in clinical guidelines. The epidemiological observation that obesity may be protective in patients with established cardiovascular disease is difficult to translate into clinical experience and practice. Weight loss is often recommended as a means to lower blood pressure. However, current hypertension guidelines do not provide evidence-based guidance on how to institute weight loss. In fact, weight loss influences on blood pressure may be overestimated. Nevertheless, weight loss through bariatric surgery appears to decrease cardiovascular risk in severely obese patients. Eventually, most obese hypertensive patients will require antihypertensive medications. Data from large-scale studies with hard clinical endpoints on antihypertensive medications specifically addressing obese patients are lacking and the morbidity from the growing population of severely obese patients is poorly recognized or addressed. Because of their broad spectrum of beneficial effects, renin-angiotensin system inhibitors are considered to be the most appropriate drugs for antihypertensive treatment of obese patients. Most obese hypertensive patients require two or more antihypertensive drugs. Finally, how to combine weight loss strategies and antihypertensive treatment to achieve an optimal clinical outcome is unresolved.

  19. Pulmonary arterial hypertension caused by treatment with dasatinib for chronic myeloid leukemia -critical alert-.

    PubMed

    Sano, Makoto; Saotome, Masao; Urushida, Tsuyoshi; Katoh, Hideki; Satoh, Hiroshi; Ohnishi, Kazunori; Hayashi, Hideharu

    2012-01-01

    We present a case of pulmonary arterial hypertension (PAH), which is potentially related to treatment with dasatinib (Sprycel(®)). A 61-year-old woman, who had been treated with dasatinib for 27 months for chronic myeloid leukemia (CML), visited our hospital complaining of dyspnea. In right heart catheterization, her mean pulmonary arterial pressure was 35 mmHg. After other possible etiologies to cause PAH were excluded, the patient was diagnosed as a dasatinib-related PAH. As notified by U.S. Food and Drug Administration (FDA) in October 2011, we recommend routine cardiopulmonary evaluation before and during treatment with dasatinib in CML patients in terms of the adverse effects of PAH. PMID:22975544

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

    PubMed

    Arita, Shinji; Arita, Noboru; Hikasa, Yoshiaki

    2013-03-01

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

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

    PubMed Central

    Arita, Shinji; Arita, Noboru; Hikasa, Yoshiaki

    2013-01-01

    This was a pilot study to determine the effectiveness of low-dose imatinib therapy for hemodynamic disturbances, including pulmonary arterial hypertension (PAH), and clinical manifestations caused by chronic heart failure in dogs. Six client-owned dogs with PAH were administered imatinib mesylate orally, 3 mg/kg body weight q24h, for 30 d. Physical examination, blood biochemical tests, radiography, and Doppler echocardiography were performed prior to imatinib administration and again 30 days after administration. Clinical scores were significantly reduced after imatinib treatment. Systolic pulmonary arterial pressure, heart rate, maximum tricuspid regurgitation velocity, left atrium/aorta ratio, right and left ventricular Tei indexes, early diastolic transmitral flow wave/mitral annulus velocity ratio, and plasma atrial natriuretic peptide concentration decreased significantly after therapy. Diastolic blood pressure, stroke volume, cardiac output, and left ventricular fractional shortening increased significantly after therapy. These results indicate that low-dose imatinib therapy was effective for heart failure in dogs with PAH. PMID:23997262

  2. Hypertensive emergency due to pheochromocytoma crisis complicated with refractory hemodynamic collapse.

    PubMed

    Hayıroğlu, Mert İlker; Yıldırımtürk, Özlem; Bozbay, Mehmet; Eren, Mehmet; Pehlivanoğlu, Seçkin

    2015-12-01

    Hypertensive emergency usually appears in older patients with previous recurrent episodes, and is among the most frequent admissions to emergency departments. A 29-year-old woman was referred to our clinic with the diagnosis of hypertensive emergency. The patient complained of severe headache, dyspnea, palpitation, diaphoresis, and confusion due to hypertensive encephalopathy. Her blood pressure was 250/150 mmHg on admission. At the referral hospital, the patient had undergone cranial CT because of her confused state and this excluded acute cerebral hemorrhage. Also at that hospital, thoracoabdominal CT for differential diagnosis depicted an adrenal mass with a necrotic core. After admission to our clinic, initial control of excessive blood pressure was not achieved despite high dose intravenous nitrate therapy. Thereafter intravenous esmolol treatment was initiated simultaneously with oral alpha blocker therapy in order to counterbalance the unopposed alpha adrenergic activity with beta blocker therapy. After 12 hours, sudden onset of hypotension developed and deepened despite IV saline, inotropic and vasopressor agents such as IV dopamine, noradrenaline and adrenaline. The patient died at the 24th hour due to hemodynamic collapse as a result of hyperadrenergic state due to possible pheochromocytoma crisis. This case is an exceptional example of hypertensive emergency secondary to fulminant pheochromocytoma crisis failing to respond to intensive antihypertensive treatment, and in which patient death was unavoidable due to uncontrolled excessive adrenergic activity which led to profound cardiogenic shock. PMID:26717337

  3. Hypertensive emergency due to pheochromocytoma crisis complicated with refractory hemodynamic collapse.

    PubMed

    Hayıroğlu, Mert İlker; Yıldırımtürk, Özlem; Bozbay, Mehmet; Eren, Mehmet; Pehlivanoğlu, Seçkin

    2015-12-01

    Hypertensive emergency usually appears in older patients with previous recurrent episodes, and is among the most frequent admissions to emergency departments. A 29-year-old woman was referred to our clinic with the diagnosis of hypertensive emergency. The patient complained of severe headache, dyspnea, palpitation, diaphoresis, and confusion due to hypertensive encephalopathy. Her blood pressure was 250/150 mmHg on admission. At the referral hospital, the patient had undergone cranial CT because of her confused state and this excluded acute cerebral hemorrhage. Also at that hospital, thoracoabdominal CT for differential diagnosis depicted an adrenal mass with a necrotic core. After admission to our clinic, initial control of excessive blood pressure was not achieved despite high dose intravenous nitrate therapy. Thereafter intravenous esmolol treatment was initiated simultaneously with oral alpha blocker therapy in order to counterbalance the unopposed alpha adrenergic activity with beta blocker therapy. After 12 hours, sudden onset of hypotension developed and deepened despite IV saline, inotropic and vasopressor agents such as IV dopamine, noradrenaline and adrenaline. The patient died at the 24th hour due to hemodynamic collapse as a result of hyperadrenergic state due to possible pheochromocytoma crisis. This case is an exceptional example of hypertensive emergency secondary to fulminant pheochromocytoma crisis failing to respond to intensive antihypertensive treatment, and in which patient death was unavoidable due to uncontrolled excessive adrenergic activity which led to profound cardiogenic shock.

  4. Acute ileofemoral artery thromboembolism due to left ventricle thrombi with spontaneous coronary artery dissection

    PubMed Central

    Jun, Heungman; Jung, Cheol-Woong

    2015-01-01

    Spontaneous coronary artery dissection (SCAD) is a very rare cause of peripheral artery thromboembolism. It is especially rare to show symptoms of acute limb ischemia without chest symptoms during a hospital visit. In this case, a rare case of SCAD led to left heart failure and caused left ventricle thrombi, which in turn caused peripheral thromboembolism. PMID:25553326

  5. Calcilytics enhance sildenafil-induced antiproliferation in idiopathic pulmonary arterial hypertension.

    PubMed

    Yamamura, Aya; Yagi, Satomi; Ohara, Naoki; Tsukamoto, Kikuo

    2016-08-01

    Idiopathic pulmonary arterial hypertension (IPAH) is a progressive and fatal disease of the pulmonary artery resulting from currently unidentified etiology. IPAH is pathologically characterized as sustained vasoconstriction and vascular remodeling of the pulmonary artery. Phosphodiesterase type 5 (PDE5) inhibitors have been clinically used in the treatment of IPAH. Recently, we have shown that Ca(2+)-sensing receptor (CaSR) antagonists, or calcilytics, inhibit excessive cell proliferation of pulmonary arterial smooth muscle cells (PASMCs) from IPAH patients. In this study, the additive or synergistic effect of calcilytics on antiproliferation following PDE5 inhibition was examined in IPAH-PASMCs by MTT assay. Treatment with sildenafil blocked the excessive cell proliferation of IPAH-PASMCs in a concentration-dependent manner with an IC50 value of 16.9μM. However, sildenafil (0.03-100μM) did not affect the cell growth of PASMCs from normal subjects and patients with chronic thromboembolic pulmonary hypertension (CTEPH). Co-treatment with 0.3μM NPS2143, a calcilytic, additively enhanced the antiproliferative effect induced by sildenafil (3 or 30μM) in IPAH-PASMCs. Additionally, the inhibitory effect of calcilytics, NPS2143 or Calhex 231 (1 or 10μM), on excessive cell proliferation of IPAH-PASMCs was synergistic increased in the presence of 1μM sildenafil. Similar results were obtained by BrdU incorporation assay. These findings reveal that calcilytics additively/synergistically enhance the antiproliferative activity mediated by PDE5 inhibition, suggesting that a combination therapy of a PDE5 inhibitor with a calcilytic may be useful as a novel therapeutic approach for IPAH. PMID:27164419

  6. Arterial hypertension in Turner syndrome: a review of the literature and a practical approach for diagnosis and treatment.

    PubMed

    De Groote, Katya; Demulier, Laurent; De Backer, Julie; De Wolf, Daniel; De Schepper, Jean; Tʼsjoen, Guy; De Backer, Tine

    2015-07-01

    Turner syndrome is a rare chromosomal disorder with complete or partial absence of one X chromosome that only occurs in women. Clinical presentation is variable, but congenital and acquired cardiovascular diseases are frequently associated diseases that add significantly to the increased morbidity and mortality in Turner syndrome patients. Arterial hypertension is reported in 13-58% of adult Turner syndrome patients and confers an increased risk for stroke and aortic dissection. Hypertension can be present from childhood on and is reported in one-quarter of the paediatric Turner syndrome patients. This article reviews the prevalence and cause of arterial hypertension in Turner syndrome and describes the relationship between blood pressure, aortic dilation and increased cardiovascular risk. We compare current treatment strategies and also propose an integrated practical approach for the diagnosis and treatment of hypertension in Turner syndrome applicable in daily practice.

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

    PubMed

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

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a chronic ailment of the lungs, exhibiting elevated arterial pressure and vascular resistance; with a mean arterial pressure above 25 mmHg at rest and above 30 mmHg during exercise. It is associated with poor prognosis, and its prevalence is estimated to be 15 cases per one million. The current treatment options for PAH are discussed with the prostanoid class of drugs being the most effective. The latter drugs act by dilating systemic and pulmonary arterial vascular beds and, with sustained long-term usage, altering pulmonary remodelling. They are administered as IV infusions or inhalation solutions. Despite their clinical effectiveness, prostanoids have short half-lives requiring frequent administration of 6-9 times daily and thus suffer from poor compliance. Controlled release inhalation delivery systems for treatment of PAH, ranging from liposomes, biodegradable nano- and microparticles, formation of co-precipitates and complexation with cyclodextrins, are explored. Arising from these formulation strategies, we developed novel polymeric microspheres for inhalation to reduce dosing frequency and improve medication compliance. These microspheres are designed with release modifiers, to reside in the lung which is the site of drug action for a longer duration so as to release the drug slowly and consistently over a prolonged period. This could lead to the development of the first commercially available controlled release inhalation product. PMID:26446472

  8. Sarcoidosis presenting as severe renin-dependent hypertension due to kidney vascular injury

    PubMed Central

    Rafat, Cedric; Bobrie, Guillaume; Chedid, Antoine; Nochy, Dominique; Hernigou, Anne; Plouin, Pierre-François

    2014-01-01

    Renal sarcoidosis embraces a wide variety of clinical patterns. Renal vascular involvement has seldom been reported and usually in the setting of systemic vasculitis. We report the case of a 22-year-old patient in whom inaugural manifestation of renal sarcoidosis consisted of severe hypertension associated with bilateral perfusion defects and tumour-like nodules. In the setting of renal sarcoidosis, our case suggests that renin-dependant hypertension may arise from renal ischaemia as a result of extrinsic compression of kidney blood vessels due to severe granulomatous inflammation. PMID:25852913

  9. The effects of quinapril and atorvastatin on artery structure and function in adult spontaneously hypertensive rats.

    PubMed

    Yang, Lufang; Gao, Yu-Jing; Lee, Robert M K W

    2005-08-22

    We studied the combined treatment effects of quinapril and atorvastatin on blood pressure and structure and function of resistance arteries from adult spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY rats). Apoptotic cells were identified by in situ end labeling using the terminal deoxynucleotide transferase-mediated dUTP nick end labeling method. Vascular structure was measured using a morphometric protocol and confocal microscopy and a pressurized artery system was used to study vascular functions. We found that a combined treatment with quinapril and atorvastatin lowered systolic blood pressure in both adult SHR and WKY rats and decreased medial thickness and volume and the number of smooth muscle cell layers in mesenteric arteries, as well as media-to-lumen ratio in the interlobular arteries from SHR but not in those from WKY rats. The number of apoptotic smooth muscle cells was higher in the mesenteric arteries from control WKY rats than control SHR and treatment increased the number of apoptotic smooth muscle cells in the arteries from both SHR and WKY rats. Treatment with quinapril and atorvastatin reduced ventricular weight in SHR and normalized the augmented contractile responses to norepinephrine but did not alter the contraction to electric field stimulation. Relaxation responses to acetylcholine and sodium nitroprusside were not affected by the treatment. We conclude that a combined treatment with quinapril and atorvastatin lowered blood pressure and improved cardiac and vessel hypertrophy and vessel function. An increase in apoptotic smooth muscle cells may be one of the mechanisms underlying the structural improvement.

  10. The relationship between occupational exposure to lead and manifestation of cardiovascular complications in persons with arterial hypertension

    SciTech Connect

    Poreba, Rafal; Gac, Pawel; Poreba, Malgorzata; Andrzejak, Ryszard

    2010-11-15

    The chronic exposure to lead represents a risk factor of arterial hypertension development. Ambulatory blood pressure monitoring is the most prognostically reliable method of measuring of arterial blood pressure. The study is aimed at evaluating the relationship between occupational exposure to lead and manifestation of cardiovascular complications in patients with arterial hypertension. The studies included 73 men (mean age, 54.26 {+-} 8.17 years) with arterial hypertension, treated with hypotensive drugs: group I-persons occupationally exposed to lead (n = 35) and group II-individuals not exposed to lead (n = 38). An analysis of results obtained during ambulatory blood pressure monitoring disclosed significantly higher values of mean systolic blood pressure, mean blood pressure, pulse pressure, and variability of systolic blood pressure in the group of hypertensive patients occupationally exposed to lead as compared to patients with arterial hypertension but not exposed to lead. The logistic regression showed that a more advanced age, higher concentration of blood zinc protoporphyrin, and a higher mean value of pulse pressure represented independent risk factors of left ventricular hypertrophy in the group of persons with arterial hypertension and chronically exposed to lead (OR{sub age} = 1.11; OR{sub ZnPP} = 1.32; OR{sub PP} = 1,43; p < 0.05). In view of the above data demonstration that occupational exposure to lead represents an independent risk factor of increased pulse pressure may be of key importance in the process of shaping general social awareness as to harmful effects of lead compounds on human health.

  11. An in vitro study of histamine on the pulmonary artery of the Wistar-Kyoto and spontaneously hypertensive rats.

    PubMed

    Lau, Wing Hung; Kwan, Yiu Wa; Au, Alice Lai Shan; Cheung, Wui Hang

    2003-05-30

    The vascular response to most neurotransmitters of different vascular beds is altered under hypertensive condition. The modulatory effect of genetic pulmonary arterial hypertension on histamine responses is not known. The present study was undertaken to evaluate the modulatory effect of enzymatic degradation (via histamine N-methyl-transferase and diamine oxidase) on the vascular response of histamine, and the subtype(s) of histamine receptor present in the pulmonary artery (first branch, O.D. approximately 800 microm) of the normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) (male, 22-26 weeks old). In phenylephrine (1 microM) pre-contracted preparations, histamine and 6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl) heptanecarboxamide (HTMT, a histamine H(1) receptor agonist) elicited a concentration-dependent relaxation, with a smaller magnitude recorded in SHR. Application of 10 microM S-[4-(N,N-dimethylamino)-butyl]isothiourea (SKF 91488, a selective histamine N-methyl-transferase inhibitor), but not aminoguanidine (100 microM, a diamine oxidase inhibitor), significantly attenuated histamine-induced relaxation. Clobenpropit (1 nM, a potent histamine H(3) receptor antagonist) "antagonised" the suppressive effect of SKF 91488 and histamine-evoked relaxation was restored. Endothelial denudation reduced histamine- and abolished HTMT-elicited relaxation. Dimaprit (a histamine H(2) receptor agonist) caused an endothelium-independent, cis-N-(2-phenylcyclopentyl)azacyclotridec-1-en-2-amine (MDL 12330A, 10 microM, an adenylate cyclase inhibitor)-sensitive, concentration-dependent relaxation, with a similar magnitude in both strains of rat. Histamine-evoked relaxation was reversed into a further contraction (clobenpropit (10 nM)-sensitive) (with a greater magnitude occurred in the WKY rat) after blocking the histamine H(1) and H(2) receptors with diphenhydramine plus cimetidine (30 microM each). A similar further contraction

  12. Cardiovascular responses induced by obstructive apnea are enhanced in hypertensive rats due to enhanced chemoreceptor responsivity.

    PubMed

    Angheben, Juliana M M; Schoorlemmer, Guus H M; Rossi, Marcio V; Silva, Thiago A; Cravo, Sergio L

    2014-01-01

    Spontaneously hypertensive rats (SHR), like patients with sleep apnea, have hypertension, increased sympathetic activity, and increased chemoreceptor drive. We investigated the role of carotid chemoreceptors in cardiovascular responses induced by obstructive apnea in awake SHR. A tracheal balloon and vascular cannulas were implanted, and a week later, apneas of 15 s each were induced. The effects of apnea were more pronounced in SHR than in control rats (Wistar Kyoto; WKY). Blood pressure increased by 57±3 mmHg during apnea in SHR and by 28±3 mmHg in WKY (p<0.05, n = 14/13). The respiratory effort increased by 53±6 mmHg in SHR and by 34±5 mmHg in WKY. The heart rate fell by 209±19 bpm in SHR and by 155±16 bpm in WKY. The carotid chemoreceptors were then inactivated by the ligation of the carotid body artery, and apneas were induced two days later. The inactivation of chemoreceptors reduced the responses to apnea and abolished the difference between SHR and controls. The apnea-induced hypertension was 11±4 mmHg in SHR and 8±4 mmHg in WKY. The respiratory effort was 15±2 mmHg in SHR and 15±2 mmHg in WKY. The heart rate fell 63±18 bpm in SHR and 52±14 bpm in WKY. Similarly, when the chemoreceptors were unloaded by the administration of 100% oxygen, the responses to apnea were reduced. In conclusion, arterial chemoreceptors contribute to the responses induced by apnea in both strains, but they are more important in SHR and account for the exaggerated responses of this strain to apnea.

  13. Micro-CT image-derived metrics quantify arterial wall distensibility reduction in a rat model of pulmonary hypertension

    NASA Astrophysics Data System (ADS)

    Johnson, Roger H.; Karau, Kelly L.; Molthen, Robert C.; Haworth, Steven T.; Dawson, Christopher A.

    2000-04-01

    We developed methods to quantify arterial structural and mechanical properties in excised rat lungs and applied them to investigate the distensibility decrease accompanying chronic hypoxia-induced pulmonary hypertension. Lungs of control and hypertensive (three weeks 11% O2) animals were excised and a contrast agent introduced before micro-CT imaging with a special purpose scanner. For each lung, four 3D image data sets were obtained, each at a different intra-arterial contrast agent pressure. Vessel segment diameters and lengths were measured at all levels in the arterial tree hierarchy, and these data used to generate features sensitive to distensibility changes. Results indicate that measurements obtained from 3D micro-CT images can be used to quantify vessel biomechanical properties in this rat model of pulmonary hypertension and that distensibility is reduced by exposure to chronic hypoxia. Mechanical properties can be assessed in a localized fashion and quantified in a spatially-resolved way or as a single parameter describing the tree as a whole. Micro-CT is a nondestructive way to rapidly assess structural and mechanical properties of arteries in small animal organs maintained in a physiological state. Quantitative features measured by this method may provide valuable insights into the mechanisms causing the elevated pressures in pulmonary hypertension of differing etiologies and should become increasingly valuable tools in the study of complex phenotypes in small-animal models of important diseases such as hypertension.

  14. [Dynamic changes in arterial hypertension prevalence and their relation to the main risk factors among able-bodied newcomers in Iamalo-Nenetskiĭ autonomous region].

    PubMed

    Shesterikova, N V; Buganov, A A; Umanskaia, E L; Novokrestova, S V

    2003-01-01

    The frequency of arterial hypertension among non-native able-bodied unorganized population of Yamalo-Nenets Autonomous Okrug was studied. Mean population index of the frequency was 31.0%. Important factors which promote arterial hypertension are excessive body mass, age, period of living in the Far North, psycho-emotional stress, unsatisfactory level of adaptation and its failure, dislipidemia.

  15. Late diagnosis of Takayasu's arteritis with repeated attacks of heart failure and uncontrolled hypertension due to abdominal aortic thrombosis: case report and review of the literature.

    PubMed

    Wang, Huan; Lai, Baochun; Wu, Xiaoying; Han, Tao; Chen, Hui

    2015-01-01

    Takayasu's arteritis (TA) is a chronic, idiopathic, inflammatory disease affecting the aorta and its branches. To date, only one case involving abdominal aortic thrombosis due to TA has been reported. After bilateral artificial subclavian-iliac bypass, a case of abdominal aortic thrombosis due to TA received a delayed diagnosis in a 44-year-old Chinese male who experienced recurrent episodes of heart failure and uncontrolled hypertension with claudication of two extremities. Abdominal color Doppler sonography and computed tomography aortography (CTA) showed occlusion of the abdominal aorta and bilateral renal artery stenosis. After vascular bypass and during 1 year follow-up, his cardiac function improved and blood pressure was well controlled, with reduced serum creatinine. Postoperative CTA still showed abdominal aortic thrombosis resulting in arterial occlusion extending from the left renal artery initial segment level to the bilateral common iliac artery and the bifurcation of the renal artery, except for the vascular bypass. Abdominal aortic thrombosis due to TA is very rare and potentially life threatening, probably becoming an atherosclerosis risk factor. Doppler sonography and CTA results are important for diagnosis. Artificial vascular bypass can be used for TA in debilitated patients with diffuse aortic disease.

  16. Prevalence of arterial hypertension among Brazilian adolescents: systematic review and meta-analysis

    PubMed Central

    2013-01-01

    the small number of studies in some regions of Brazil, the pooled prevalence found in both males and females shows that systemic arterial hypertension should be monitored in the population aged 10–20 years and that specific measures are required to prevent and control the disease, as well as its risk factors. Studies that compare regional heterogeneities may contribute to the knowledge of factors associated with increased blood pressure among adolescents. PMID:24025095

  17. [Use of computerized tomography in the study of the etiology of various forms of symptomatic arterial hypertension].

    PubMed

    Shapkina, L S; Pogrebnaia, G N; Tolua, F I

    1988-01-01

    In 181 patients with arterial hypertension of various genesis clinical-laboratory data were compared with those obtained by computed tomography of kidneys and adrenal glands for etiology verification. Computer tomography is proved to be a valuable noninvasive method for elucidation of retroperitoneal space organs pathology which can cause arterial hypertension. Hormonal-active tumors are better identified when patients are purposely selected according to the catecholamine and VMA levels as well as the state of renin-angiotensin-aldosterone system. Computer tomography allowed determination of alterations in kidneys including those not identifiable by other methods (small cysts in kidneys, tumors, concrements).

  18. Arterial microanatomy determines the success of energy-based renal denervation in controlling hypertension

    PubMed Central

    Tzafriri, Abraham R.; Keating, John H.; Markham, Peter M.; Spognardi, Anna-Maria; Stanley, James R. L.; Wong, Gee; Zani, Brett G.; Grunewald, Debby; O’Fallon, Patrick; Fuimaono, Kristine; Mahfoud, Felix; Edelman, Elazer R.

    2015-01-01

    Renal Denervation (RDN) is a treatment option for patients with hypertension resistant to conventional therapy. Clinical trials have demonstrated variable benefit. To understand the determinants of successful clinical response to this treatment, we integrated porcine and computational models of intravascular radiofrequency RDN. Controlled single-electrode denervation resulted in ablation zone geometries that varied in arc, area and depth, depending on the composition of the adjacent tissue substructure. Computational simulations predicted that delivered power density was influenced by tissue substructure, and peaked at the conductivity discontinuities between soft fatty adventitia and water rich tissues (media, lymph nodes etc.), not at the electrode-tissue interface). Electrode irrigation protected arterial wall tissue adjacent to the electrode by clearing heat that diffuses from within the tissue, without altering peri-arterial ablation. Seven days after multi-electrode treatments, renal norepinephrine and blood pressure were reduced. Blood pressure reductions were correlated with the size-weighted number of degenerative nerves, implying that the effectiveness of the treatment in decreasing hypertension depends on the extent of nerve injury and ablation, which in turn are determined by the tissue microanatomy at the electrode site. These results may explain the variable patient response to RDN and suggest a path to more robust outcomes. PMID:25925684

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

    PubMed

    Delcroix, Marion; Howard, Luke

    2015-12-01

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

  20. A study of aspirin and clopidogrel in idiopathic pulmonary arterial hypertension.

    PubMed

    Robbins, I M; Kawut, S M; Yung, D; Reilly, M P; Lloyd, W; Cunningham, G; Loscalzo, J; Kimmel, S E; Christman, B W; Barst, R J

    2006-03-01

    Idiopathic pulmonary arterial hypertension (IPAH) is characterised by in situ thrombosis and increased thromboxane (Tx) A2 synthesis; however, there are no studies of antiplatelet therapy in IPAH. The aim of the current study was to determine the biochemical effects of aspirin (ASA) and clopidogrel on platelet function and eicosanoid metabolism in patients with IPAH. A randomised, double-blind, placebo-controlled crossover study of ASA 81 mg once daily and clopidogrel 75 mg once daily was performed. Plasma P-selectin levels and aggregometry were measured after exposure to adenosine diphosphate, arachidonic acid and collagen. Serum levels of TxB2 and urinary metabolites of TxA2 and prostaglandin I2 (Tx-M and PGI-M, respectively) were assessed. A total of 19 IPAH patients were enrolled, of whom nine were being treated with continuous intravenous epoprostenol. ASA and clopidogrel significantly reduced platelet aggregation to arachidonic acid and adenosine diphosphate, respectively. ASA significantly decreased serum TxB2, urinary Tx-M levels and the Tx-M/PGI-M ratio, whereas clopidogrel had no effect on eicosanoid levels. Neither drug significantly lowered plasma P-selectin levels. Epoprostenol use did not affect the results. In conclusion, aspirin and clopidogrel inhibited platelet aggregation, and aspirin reduced thromboxane metabolite production without affecting prostaglandin I2 metabolite synthesis. Further clinical trials of aspirin in patients with idiopathic pulmonary arterial hypertension should be performed. PMID:16507859

  1. Leptin and regulatory T-lymphocytes in idiopathic pulmonary arterial hypertension.

    PubMed

    Huertas, Alice; Tu, Ly; Gambaryan, Natalia; Girerd, Barbara; Perros, Frédéric; Montani, David; Fabre, Dominique; Fadel, Elie; Eddahibi, Saadia; Cohen-Kaminsky, Sylvia; Guignabert, Christophe; Humbert, Marc

    2012-10-01

    Immune mechanisms and autoimmunity seem to play a significant role in idiopathic pulmonary arterial hypertension (IPAH) pathogenesis and/or progression, but the pathophysiology is still unclear. Recent evidence has demonstrated a detrimental involvement of leptin in promoting various autoimmune diseases by controlling regulatory T-lymphocytes. Despite this knowledge, the role of leptin in IPAH is currently unknown. We hypothesised that leptin, synthesised by dysfunctional pulmonary endothelium, might play a role in the immunopathogenesis of IPAH by regulating circulating regulatory T-lymphocytes function. First, we collected serum and regulatory T-lymphocytes from controls, and IPAH and scleroderma-associated pulmonary arterial hypertension (SSc-PAH) patients; secondly, we recovered tissue samples and cultured endothelial cells after either surgery or transplantation in controls and IPAH patients, respectively. Our findings indicate that serum leptin was higher in IPAH and SSc-PAH patients than controls. Circulating regulatory T-lymphocyte numbers were comparable in all groups, and the percentage of those expressing leptin receptor was higher in IPAH and SSc-PAH compared with controls, whereas their function was reduced in IPAH and SSc-PAH patients compared with controls, in a leptin-dependent manner. Furthermore, endothelial cells from IPAH patients synthesised more leptin than controls. Our data suggest that endothelial-derived leptin may play a role in the immunopathogenesis of IPAH. PMID:22362850

  2. Safety, efficacy, and clinical utility of macitentan in the treatment of pulmonary arterial hypertension.

    PubMed

    Monaco, Thomas J; Davila, Carlos D

    2016-01-01

    Pulmonary arterial hypertension is a progressive, debilitating disease caused by a dysregulation of the pulmonary vascular tone that inevitably leads to right heart failure and death without treatment. Until relatively recently, the treatment options for those afflicted by pulmonary arterial hypertension were limited; today, a greater understanding of the pathophysiology behind this disease has led to several evidence-based therapies that can improve pulmonary function and quality of life for these patients. One of the primary mediators of pulmonary vascular tone is endothelin-1, which is a potent and long-lasting vasoconstrictor. Macitentan is a second-generation endothelin receptor antagonist that acts selectively as a pulmonary vasodilator without the significant side effects noted with previous endothelin receptor antagonists. This review focuses on the mechanism of action and pharmacokinetics of macitentan, as well as the adverse effects, efficacy, and clinical uses of macitentan in the clinical trials to date. In addition, the authors briefly review clinical trials currently underway to illustrate possible future directions for the use of macitentan.

  3. Safety, efficacy, and clinical utility of macitentan in the treatment of pulmonary arterial hypertension

    PubMed Central

    Monaco, Thomas J; Davila, Carlos D

    2016-01-01

    Pulmonary arterial hypertension is a progressive, debilitating disease caused by a dysregulation of the pulmonary vascular tone that inevitably leads to right heart failure and death without treatment. Until relatively recently, the treatment options for those afflicted by pulmonary arterial hypertension were limited; today, a greater understanding of the pathophysiology behind this disease has led to several evidence-based therapies that can improve pulmonary function and quality of life for these patients. One of the primary mediators of pulmonary vascular tone is endothelin-1, which is a potent and long-lasting vasoconstrictor. Macitentan is a second-generation endothelin receptor antagonist that acts selectively as a pulmonary vasodilator without the significant side effects noted with previous endothelin receptor antagonists. This review focuses on the mechanism of action and pharmacokinetics of macitentan, as well as the adverse effects, efficacy, and clinical uses of macitentan in the clinical trials to date. In addition, the authors briefly review clinical trials currently underway to illustrate possible future directions for the use of macitentan. PMID:27274200

  4. [Features of brain oscillatory activity and cardiac defense in treatment arterial hypertensives].

    PubMed

    Aftanas, L I; Brak, I V; Gilinskaia, O M; Pavlov, S V; Reva, N V

    2014-01-01

    Stress reactivity of the motivational system of defense can be assessed with the aid the cardiac defense response (CDR) - the reaction of the cardiovascular system to unexpected aversive unconditioned stimulus. The main objective of the study was revealing putative contribution of oscillatory systems of the brain into central pathogenic mechanisms of enhanced blood pressure (BP) stress-reactivity in naive patients with arterial hypertension (AH) of the 1st-2nd degrees (n = 17) and healthy control (n = 19) subjects. Using dynamic registration "beat-by-beat" arterial pressure, and oscillatory activity related EEG (64 channels) is estimated using the event-related synchronization/desynchronization (ERD/ERS). Along with abnormally high blood pressure in patients with hypertension background set significantly lower concentrations of serotonin blood platelets and increased tonic activation of the left hemisphere, reflected in the asymmetric reduction of delta- (2-4 Hz) and theta-1 (4-6 Hz) power in the central and parietal cortex in the hemisphere CDR of the patients are characterized by hyperactivity both short- and long-latency components of blood pressure. According to the dynamic analysis of the concomitant EEG, long-latency BP components may be accounted by, among other mechanisms, weakening of the descending ("top-down") inhibitory control, hypothetically implemented with the high-frequency EEG alpha (10-12 Hz) oscillations from the medial central-parietal cortex of both hemispheres of the brain. PMID:25464727

  5. Vasovagal response secondary to permanent contraception device in pulmonary arterial hypertension

    PubMed Central

    Cope, Jessica; Alnuaimat, Hassan

    2015-01-01

    Abstract Adequate contraception is an essential component of managing pulmonary hypertension in women of childbearing age. Intrauterine devices are a popular contraceptive choice for many women but are associated with a risk of vagal response upon placement in certain patients with pulmonary hypertension, which may not be well tolerated. More recently, newer permanent contraception devices have emerged in the market, such as the Essure. We describe the first case, to our knowledge, of vagal-associated response due to an Essure device placement. PMID:26697184

  6. Blunted sympathoinhibitory responses in obesity-related hypertension are due to aberrant central but not peripheral signalling mechanisms

    PubMed Central

    How, Jackie M Y; Wardak, Suhail A; Ameer, Shaik I; Davey, Rachel A; Sartor, Daniela M

    2014-01-01

    The gut hormone cholecystokinin (CCK) acts at subdiaphragmatic vagal afferents to induce renal and splanchnic sympathoinhibition and vasodilatation, via reflex inhibition of a subclass of cardiovascular-controlling neurons in the rostroventrolateral medulla (RVLM). These sympathoinhibitory and vasodilator responses are blunted in obese, hypertensive rats and our aim in the present study was to determine whether this is attributable to (i) altered sensitivity of presympathetic vasomotor RVLM neurons, and (ii) aberrant peripheral or central signalling mechanisms. Using a diet-induced obesity model, male Sprague–Dawley rats exhibited either an obesity-prone (OP) or obesity-resistant (OR) phenotype when placed on a medium high fat diet for 13–15 weeks; control animals were placed on a low fat diet. OP animals had elevated resting arterial pressure compared to OR/control animals (P < 0.05). Barosensitivity of RVLM neurons was significantly attenuated in OP animals (P < 0.05), suggesting altered baroreflex gain. CCK induced inhibitory responses in RVLM neurons of OR/control animals but not OP animals. Subdiaphragmatic vagal nerve responsiveness to CCK and CCK1 receptor mRNA expression in nodose ganglia did not differ between the groups, but CCK induced significantly less Fos-like immunoreactivity in both the nucleus of the solitary tract and the caudal ventrolateral medulla of OP animals compared to controls (P < 0.05). These results suggest that blunted sympathoinhibitory and vasodilator responses in obesity-related hypertension are due to alterations in RVLM neuronal responses, resulting from aberrant central but not peripheral signalling mechanisms. In obesity, blunted sympathoinhibitory mechanisms may lead to increased regional vascular resistance and contribute to the development of hypertension. PMID:24492842

  7. Blunted sympathoinhibitory responses in obesity-related hypertension are due to aberrant central but not peripheral signalling mechanisms.

    PubMed

    How, Jackie M Y; Wardak, Suhail A; Ameer, Shaik I; Davey, Rachel A; Sartor, Daniela M

    2014-04-01

    The gut hormone cholecystokinin (CCK) acts at subdiaphragmatic vagal afferents to induce renal and splanchnic sympathoinhibition and vasodilatation, via reflex inhibition of a subclass of cardiovascular-controlling neurons in the rostroventrolateral medulla (RVLM). These sympathoinhibitory and vasodilator responses are blunted in obese, hypertensive rats and our aim in the present study was to determine whether this is attributable to (i) altered sensitivity of presympathetic vasomotor RVLM neurons, and (ii) aberrant peripheral or central signalling mechanisms. Using a diet-induced obesity model, male Sprague-Dawley rats exhibited either an obesity-prone (OP) or obesity-resistant (OR) phenotype when placed on a medium high fat diet for 13-15 weeks; control animals were placed on a low fat diet. OP animals had elevated resting arterial pressure compared to OR/control animals (P < 0.05). Barosensitivity of RVLM neurons was significantly attenuated in OP animals (P < 0.05), suggesting altered baroreflex gain. CCK induced inhibitory responses in RVLM neurons of OR/control animals but not OP animals. Subdiaphragmatic vagal nerve responsiveness to CCK and CCK1 receptor mRNA expression in nodose ganglia did not differ between the groups, but CCK induced significantly less Fos-like immunoreactivity in both the nucleus of the solitary tract and the caudal ventrolateral medulla of OP animals compared to controls (P < 0.05). These results suggest that blunted sympathoinhibitory and vasodilator responses in obesity-related hypertension are due to alterations in RVLM neuronal responses, resulting from aberrant central but not peripheral signalling mechanisms. In obesity, blunted sympathoinhibitory mechanisms may lead to increased regional vascular resistance and contribute to the development of hypertension.

  8. Doxazosin: safety and efficacy in the treatment of resistant arterial hypertension.

    PubMed

    Ceral, Jiri; Solar, Miroslav

    2009-01-01

    Five classes of antihypertensive drugs have proven efficacy in the prevention of cardiovascular morbidity and mortality. Among the remaining antihypertensives, the action of alpha-1-blockers is supported by most clinical evidence; however, in combination therapy, the published data concern their use as third-line drugs at the most. The data from patients with drug-resistant hypertension remain limited. The aim of our study was to evaluate the efficacy and safety of doxazosin in this clinical setting. Data from 97 patients with resistant hypertension treated by doxazosin were analysed retrospectively. Doxazosin was usually added as the fifth antihypertensive drug in individuals who were either unresponsive to or intolerant of the combination of other antihypertensives. The dose of doxazosin ranged from 2 to 16 mg/day. The mean duration of follow-up was 21+/-17 months. Adverse events related to doxazosin treatment were rare and led to discontinuation of the therapy in only five patients (5.2%). Data from 34 patients were subjected to analysis of efficacy. In this subgroup, doxazosin therapy led to the reduction of blood pressure from 159+/-20/92+/-14 to 126+/-16/73+/-10 mmHg. We found that doxazosin is a well-tolerated and effective drug for patients with resistant arterial hypertension who require a combination of multiple antihypertensive drugs.

  9. The role of endogenous cardiotonic steroids in pathogenesis of cardiovascular and renal complications of arterial hypertension.

    PubMed

    Paczula, Aneta; Więcek, Andrzej; Piecha, Grzegorz

    2016-01-01

    Endogenous cardiotonic steroids (CTS), also called digitalis-like factors, are a group of steroid hormones linking high salt intake and elevated blood pressure and in part responsible for target organ damage in arterial hypertension. CTS act primarily through their ability to inhibit the ubiquitous transport enzyme sodium-potassium adenosine triphosphatase (Na⁺/K⁺-ATPase). A portion of Na⁺/K⁺-ATPase does not seem to actively "pump" sodium and potassium but is closely associated with other key signaling proteins. Plasma concentration and urine excretion of CTS are increased in experimental models with volume expansion and on a high salt diet. Elevated plasma concentration of marinobufagenin has been shown in volume-expanded states such as essential hypertension, primary aldosteronism, chronic renal failure, congestive heart failure and pregnancy. In experimental models marinobufagenin induces heart and kidney fibrosis to the same extent as observed in uremia. Neutralization of marinobufagenin with antibodies prevents such heart remodeling. Expanding our understanding of this new class of hormones may lead to development of novel and effective therapeutic strategies in hypertensive patients with renal and cardiovascular complications. PMID:27117099

  10. The role of endogenous cardiotonic steroids in pathogenesis of cardiovascular and renal complications of arterial hypertension.

    PubMed

    Paczula, Aneta; Więcek, Andrzej; Piecha, Grzegorz

    2016-03-18

    Endogenous cardiotonic steroids (CTS), also called digitalis-like factors, are a group of steroid hormones linking high salt intake and elevated blood pressure and in part responsible for target organ damage in arterial hypertension. CTS act primarily through their ability to inhibit the ubiquitous transport enzyme sodium-potassium adenosine triphosphatase (Na⁺/K⁺-ATPase). A portion of Na⁺/K⁺-ATPase does not seem to actively "pump" sodium and potassium but is closely associated with other key signaling proteins. Plasma concentration and urine excretion of CTS are increased in experimental models with volume expansion and on a high salt diet. Elevated plasma concentration of marinobufagenin has been shown in volume-expanded states such as essential hypertension, primary aldosteronism, chronic renal failure, congestive heart failure and pregnancy. In experimental models marinobufagenin induces heart and kidney fibrosis to the same extent as observed in uremia. Neutralization of marinobufagenin with antibodies prevents such heart remodeling. Expanding our understanding of this new class of hormones may lead to development of novel and effective therapeutic strategies in hypertensive patients with renal and cardiovascular complications.

  11. Sympathoexcitation by oxidative stress in the brain mediates arterial pressure elevation in salt-sensitive hypertension.

    PubMed

    Fujita, Megumi; Ando, Katsuyuki; Nagae, Ai; Fujita, Toshiro

    2007-08-01

    Central sympathoexcitation is involved in the pathogenesis of salt-sensitive hypertension. We have suggested that oxidative stress in the brain modulates the sympathetic regulation of arterial pressure. Thus, we investigated whether oxidative stress could mediate central sympathoexcitation in salt-sensitive hypertension. Five- to 6-week-old male Dahl salt-sensitive rats and salt-resistant rats were fed with a normal (0.3%) or high- (8%) salt diet for 4 weeks. In urethane-anesthetized and artificially ventilated rats, arterial pressure, renal sympathetic nerve activity, and heart rate decreased in a dose-dependent fashion, when 20 or 40 micromol of tempol, a membrane-permeable superoxide dismutase mimetic, was infused into the lateral cerebral ventricle. The same degree of reduction was noted in salt-sensitive and salt-resistant rats without salt loading. Salt loading significantly increased central tempol-induced reductions in arterial pressure (-29.1+/-4.8% versus -10.6+/-3.3% at 40 micromol; P<0.01), sympathetic nerve activity (-18.7+/-2.0% versus -7.1+/-1.8%; P<0.01), and heart rate (-10.7+/-2.8% versus -2.0+/-0.7%; P<0.05) in salt-sensitive rats but not in salt-resistant rats. Intracerebroventricular diphenyleneiodonium, a reduced nicotinamide-adenine dinucleotide phosphate oxidase inhibitor, also elicited significantly greater reduction in each parameter in salt-loaded salt-sensitive rats. Moreover, salt loading increased reduced nicotinamide-adenine dinucleotide phosphate-dependent superoxide production in the hypothalamus in salt-sensitive rats but not in salt-resistant rats. In addition, reduced nicotinamide-adenine dinucleotide phosphate oxidase subunits p22(phox), p47(phox), and gp91(phox) mRNA expression significantly increased in the hypothalamus of salt-loaded salt-sensitive rats. In conclusion, in salt-sensitive hypertension, increased oxidative stress in the brain, possibly via activation of reduced nicotinamide-adenine dinucleotide phosphate oxidase

  12. 2014 Guidelines of Taiwan Society of Cardiology (TSOC) for the Management of Pulmonary Arterial Hypertension

    PubMed Central

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

    2014-01-01

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

  13. Hypertension and coronary artery disease: a summary of the American Heart Association scientific statement.

    PubMed

    Rosendorff, Clive

    2007-10-01

    The American Heart Association scientific statement on the treatment of hypertension in the prevention and management of ischemic heart disease was published recently. The main recommendations were as follows: (1) For most adults with hypertension, the blood pressure (BP) goal is <140/90 mm Hg but should be <130/80 [corrected] mm Hg in patients with diabetes mellitus, chronic kidney disease, known coronary artery disease (CAD), CAD equivalents (carotid artery disease, abdominal aortic aneurism, and peripheral vascular disease), or 10-year Framingham risk score of >/=10%. For those with left ventricular dysfunction, the recommended BP target is <120/80 mm Hg. (2) For primary CAD prevention, any effective antihypertensive drug or combination is indicated, but preference is given to angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and thiazide diuretics. (3) For the management of hypertension in patients with established CAD (stable or unstable angina, non-ST-segment elevation myocardial infarction, ST-segment elevation myocardial infarction), beta-blockers and ACE inhibitors (or ARBs) are the basis of treatment. If further BP lowering is needed, a thiazide diuretic and/or a dihydropyridine CCB (not verapamil or diltiazem) can be added. If a beta-blocker is contraindicated or not tolerated, diltiazem or verapamil can be substituted. (4) If there is left ventricular dysfunction, recommended therapy consists of an ACE inhibitor or ARB, a beta-blocker, and either a thiazide or loop diuretic. In patients with more severe heart failure, an aldosterone antagonist and hydralazine/isosorbide dinitrate (in black patients) should be considered. PMID:17917507

  14. Frequency of supraventricular arrhythmias in patients with idiopathic pulmonary arterial hypertension.

    PubMed

    Wen, Li; Sun, Ming-Li; An, Pei; Jiang, Xin; Sun, Kai; Zheng, Lu; Liu, Qian-Qian; Wang, Lan; Zhao, Qin-Hua; He, Jing; Jing, Zhi-Cheng

    2014-11-01

    Supraventricular arrhythmias (SVA) may be risk factors of prognosis in patients with pulmonary arterial hypertension. SVA are increasingly reported in patients with pulmonary hypertension, but little is known about their incidence and outcomes for patients with idiopathic pulmonary arterial hypertension (IPAH) in a large cohort. In this 6-year prospective multicenter study, 280 patients with IPAH were enrolled to investigate the incidence of SVA and assess risk factors, clinical manifestation, management, and impact on survival. The cumulative 6-year incidence of SVA was 15.8%. The most common types of SVA were atrial fibrillation (n = 16) and atrial flutter (n = 13), followed by atrial tachycardia (n = 11). Most episodes of SVA were associated with significant clinical deterioration and right-sided cardiac failure. Sinus rhythm was successfully restored in most patients, resulting in clinical recovery. Increased right ventricular diameter, left atrial area, and higher right atrial pressure and pulmonary vascular resistance were associated with increased risk for experiencing SVA. SVA predicted a greater risk for mortality in a stepwise forward Cox analysis (hazard ratio 4.757, 95% confidence interval 2.695 to 8.397, p <0.001). Kaplan-Meier survival curves showed that patients with SVA, mainly permanent SVA, had a lower survival rate than those who did not develop SVA (p = 0.008). In conclusion, SVA often lead to clinical deterioration and may be associated with an increased risk for death in a large cohort of patients with IPAH. Restoration and maintenance of sinus rhythm are important treatment goals in patients with IPAH.

  15. Acute Carotid Artery Stent Thrombosis Due to Dual Antiplatelet Resistance

    SciTech Connect

    Köklü, Erkan Arslan, Şakir; Yüksel, İsa Öner; Bayar, Nermin; Koç, Pınar

    2015-08-15

    Carotid artery stenting (CAS) is a revascularization modality that is an alternative to carotid endarterectomy. The efficacy of CAS in primary and secondary prevention from ischemic stroke has been demonstrated in various trials. Acute thrombosis of CAS is a rare complication that can lead to dramatic and catastrophic consequences. We discuss a case of acute CAS thrombosis in a patient who had previously undergone successful CAS. CAS was performed in a 73-year-old man who had had dysarthria lasting 2 weeks with 95 % stenosis in his left internal carotid artery. An acute cerebrovascular event resulting in right-sided hemiplegia developed 24 h after the procedure. Computed tomographic carotid angiography revealed complete occlusion of the stent with thrombus. The cause of stent thrombosis was thought to be antiaggregant resistance to both acetylsalicylic acid and clopidogrel. The most important cause of acute CAS thrombosis is inadequate or ineffective antiaggregant therapy. Evaluating patients who are candidates for CAS for acetylsalicylic acid and clopidogrel resistance may preclude this complication.

  16. The role of collagen in extralobar pulmonary artery stiffening in response to hypoxia-induced pulmonary hypertension.

    PubMed

    Ooi, Chen Yen; Wang, Zhijie; Tabima, Diana M; Eickhoff, Jens C; Chesler, Naomi C

    2010-12-01

    Hypoxic pulmonary hypertension (HPH) causes extralobar pulmonary artery (PA) stiffening, which potentially impairs right ventricular systolic function. Changes in the extracellular matrix proteins collagen and elastin have been suggested to contribute to this arterial stiffening. We hypothesized that vascular collagen accumulation is a major cause of extralobar PA stiffening in HPH and tested our hypothesis with transgenic mice that synthesize collagen type I resistant to collagenase degradation (Col1a1(R/R)). These mice and littermate controls that have normal collagen degradation (Col1a1(+/+)) were exposed to hypoxia for 10 days; some were allowed to recover for 32 days. In vivo PA pressure and isolated PA mechanical properties and collagen and elastin content were measured for all groups. Vasoactive studies were also performed with U-46619, Y-27632, or calcium- and magnesium-free medium. Pulmonary hypertension occurred in both mouse strains due to chronic hypoxia and resolved with recovery. HPH caused significant PA mechanical changes in both mouse strains: circumferential stretch decreased, and mid-to-high-strain circumferential elastic modulus increased (P < 0.05 for both). Impaired collagen type I degradation prevented a return to baseline mechanical properties with recovery and, in fact, led to an increase in the low and mid-to-high-strain moduli compared with hypoxia (P < 0.05 for both). Significant changes in collagen content were found, which tended to follow changes in mid-to-high-strain elastic modulus. No significant changes in elastin content or vasoactivity were observed. Our results demonstrate that collagen content is important to extralobar PA stiffening caused by chronic hypoxia. PMID:20852040

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

    PubMed

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

    2016-06-01

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

  18. The role of collagen in extralobar pulmonary artery stiffening in response to hypoxia-induced pulmonary hypertension

    PubMed Central

    Ooi, Chen Yen; Wang, Zhijie; Tabima, Diana M.; Eickhoff, Jens C.

    2010-01-01

    Hypoxic pulmonary hypertension (HPH) causes extralobar pulmonary artery (PA) stiffening, which potentially impairs right ventricular systolic function. Changes in the extracellular matrix proteins collagen and elastin have been suggested to contribute to this arterial stiffening. We hypothesized that vascular collagen accumulation is a major cause of extralobar PA stiffening in HPH and tested our hypothesis with transgenic mice that synthesize collagen type I resistant to collagenase degradation (Col1a1R/R). These mice and littermate controls that have normal collagen degradation (Col1a1+/+) were exposed to hypoxia for 10 days; some were allowed to recover for 32 days. In vivo PA pressure and isolated PA mechanical properties and collagen and elastin content were measured for all groups. Vasoactive studies were also performed with U-46619, Y-27632, or calcium- and magnesium-free medium. Pulmonary hypertension occurred in both mouse strains due to chronic hypoxia and resolved with recovery. HPH caused significant PA mechanical changes in both mouse strains: circumferential stretch decreased, and mid-to-high-strain circumferential elastic modulus increased (P < 0.05 for both). Impaired collagen type I degradation prevented a return to baseline mechanical properties with recovery and, in fact, led to an increase in the low and mid-to-high-strain moduli compared with hypoxia (P < 0.05 for both). Significant changes in collagen content were found, which tended to follow changes in mid-to-high-strain elastic modulus. No significant changes in elastin content or vasoactivity were observed. Our results demonstrate that collagen content is important to extralobar PA stiffening caused by chronic hypoxia. PMID:20852040

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

    PubMed

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

    2016-06-01

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

  20. Arterial desaturation due to pulmonary arteriovenous malformations after the Kawashima Operation.

    PubMed

    Loomba, Rohit S

    2016-01-01

    Arterial desaturation may occur after the Kawashima procedure and, in the absence of venovenous collaterals is usually due to pulmonary arteriovenous malformations. Stenting of the pulmonary arteries, oxygen therapy, and pulmonary vasodilators such as sildenafil have not been able to resolve the arterial desaturation and the only way to do this has been Fontan completion. The time course of the formation of these malformations after the Kawashima and the progression of cyanosis and its resolution after the Fontan has only been demonstrated in case reports and small case series. We pool the available data to model arterial saturations in patients with pulmonary arteriovenous malformations after the Kawashima procedure. PMID:27011689

  1. Pseudoaneurysm of the Common Carotid Artery in an Infant due to Swallowed Fish Bone

    PubMed Central

    Jean Roger, Moulion Tapouh; Marcus, Fokou; Emmanuel, Fongang; Boniface, Moifo; Alain Georges, Juimo

    2015-01-01

    Carotid artery pseudoaneurysm is a rare condition, particularly in the paediatric population. Only about 30 cases of carotid artery aneurysms in infants have been published until now. This paper reports the case of a giant pseudoaneurysm of the left common carotid artery due to swallowed fish bone by an 8-year-old boy. This pseudoaneurysm was 5.5 cm transverse-diameter and resulted in severe respiratory distress. It was treated by resection and end-to-end anastomosis with satisfactory outcome after one-year follow-up. To the best of our knowledge, this is the largest carotid artery pseudoaneurysm ever described in children. PMID:26783485

  2. Pseudoaneurysm of the Common Carotid Artery in an Infant due to Swallowed Fish Bone.

    PubMed

    Jean Roger, Moulion Tapouh; Marcus, Fokou; Emmanuel, Fongang; Boniface, Moifo; Alain Georges, Juimo

    2015-01-01

    Carotid artery pseudoaneurysm is a rare condition, particularly in the paediatric population. Only about 30 cases of carotid artery aneurysms in infants have been published until now. This paper reports the case of a giant pseudoaneurysm of the left common carotid artery due to swallowed fish bone by an 8-year-old boy. This pseudoaneurysm was 5.5 cm transverse-diameter and resulted in severe respiratory distress. It was treated by resection and end-to-end anastomosis with satisfactory outcome after one-year follow-up. To the best of our knowledge, this is the largest carotid artery pseudoaneurysm ever described in children.

  3. Interlobular arteries from two-kidney, one-clip Goldblatt hypertensive rats exhibit impaired vasodilator response to epoxyeicosatrienoic acids

    PubMed Central

    Sporková, Alexandra; Reddy, N. Rami; Falck, John R.; Imig, John D.; Kopkan, Libor; Sadowski, Janusz; Červenka, Luděk

    2016-01-01

    Background Small renal arteries have a significant role in regulation of renal hemodynamics and blood pressure (BP). To study potential changes in regulation of vascular function in hypertension, we examined renal vasodilatory responses of small arteries from nonclipped kidneys of the two-kidney, one-clip (2K1C) Goldblatt hypertensive rats to native epoxyeicosatrienoic acids (EETs) which are believed to be involved in regulation of renal vascular function and BP. Two newly synthesized EET analogs were also examined. Methods Renal interlobular arteries isolated from the nonclipped kidneys on day 28 after clipping were preconstricted with phenylephrine (PE), pressurized, and the effects of a 14,15-EET analog, native 14,15-EET, and 11,12-ether-EET-8ZE, an analog of 11,12-EET, on the vascular diameter were determined and compared to the responses of arteries from the kidneys of sham-operated rats. Results In the arteries from non-clipped kidneys isolated in the maintenance phase of Goldblatt hypertension the maximal vasodilatory response to 14,15-EET analog was 30.1 ± 2.8% versus 49.8 ± 7.2% in sham-operated rats; the respective values for 11,12-ther-EET-8ZE were 31.4± 6.4% versus 80.4±6%, and for native EETs they were 41.7 ± 6.6 % versus 62.8 ± 4.4 % (P ≤ 0.05 for each difference). Conclusions We propose that reduced vasodilatory action and decreased intrarenal bioavailability of EETs combined with intrarenal ANG II levels that are inappropriately high for hypertensive rats underlie functional derangements of the nonclipped kidneys of 2K1C Goldblatt hypertensive rats. These derangements could play an important role in pathophysiology of sustained BP elevation observed in this animal model of human renovascular hypertension. PMID:27140711

  4. [IDENTIFICATION OF OCCUPATIONAL RISK FOR ARTERIAL HYPERTENSION. REPORT II: ELIMINATION OF THE MODIFYNG INFLUENCE OF FACTORS OF CARDIOVASCULAR RISK].

    PubMed

    Maksimov, S A; Skripchenko, A E; Mikhailuts, A P; Artamonova, G V

    2016-01-01

    This study is a continuation of (Report I) identification of the occupational risk of arterial hypertension (AH) in 13 occupational groups (3842 workers, men). In previous work there was eliminated the influence of traditional factors of the cardiovascular risk, in this study there was implemented the identification of the components of a healthy worker effect (HWE) and the elimination of their influence on the occupational risks of hypertension. Identification and removal of components HWE--the effect of a healthy recruitment (EHR) and the effect of the healthy worker persisting to work (EHWPW--was carried out by the analytic rearranging of the standardized for age and obesity prevalence rate of arterial hypertension with the use of own methodological approaches. For the determination of the presence and severity of EHR there was performed an analysis of the initial prevalence rate of arterial hypertension in the youngest age groups (under 31 years). To overcome HER standardized for age and obesity indices of the arterial hypertension prevalence rate were adjusted by the ratio of the frequency of arterial hypertension in the most young occupational and reference comparable groups. Identification of HWPW was executed by comparing the frequency of AH among workers retiring within 3 years from the occupational groups when compared to the whole sample. Then on the additional risk value there was adjusted the overall prevalence rate of AH in the occupation profession to overcome EHWPW. As a result of the consistent correction and elimination of the influence of HWE components on the prevalence rate of AH, there were obtained risks values, primarily reflecting the impact of occupational factors which can be considered as true occupational risks. Factors of the cardiovascular risk and HWE significantly modified true occupational risks for AH in a number of occupational groups up to inversion. At the same time, the pronouncement of EHR has a paramount importance in the

  5. Efficacy and safety of mineralocorticoid receptors in mild to moderate arterial hypertension.

    PubMed

    Pelliccia, Francesco; Rosano, Giuseppe; Patti, Giuseppe; Volterrani, Maurizio; Greco, Cesare; Gaudio, Carlo

    2015-12-01

    The mineralocorticoid receptor antagonists have been shown to have favourable safety and cost-effectiveness profiles across a broad range of clinical indications, including heart failure, primary aldosteronism and resistant hypertension. The clinical biology of the first aldosterone blocker, i.e. spironolactone, and its effects in several organ systems has been well elucidated from multiple studies. The range of adverse effects experienced with spironolactone has led to its modification and the consequent synthesis of eplerenone. Scientific evidence accumulated so far supports the role of eplerenone as first-choice drug in heart failure, with lower prevalence rates of sex-related adverse effects associated with eplerenone as compared to spironolactone. In Europe, eplerenone is currently marketed only in some countries and only with the indication of heart failure, whereas its clinical efficacy and safety in mild to moderate hypertension is said to be uncertain. A review of available scientific evidence, however, discloses that 11 randomized clinical trials assessing eplerenone in >3500 hypertensives have been reported so far. The results of these studies clearly show that eplerenone is an effective antihypertensive agent when used alone or in combination with other medications. In doses ranging from 25 to 100mg daily, eplerenone monotherapy results in a dose-dependent reduction in clinic blood pressure. As compared to placebo, eplerenone reduces significantly blood pressure from baseline. In general, 100mg daily eplerenone has a blood pressure lowering that is 50 to 75% that of spironolactone. Eplerenone results in a greater reduction in blood pressure as compared with losartan, and comparison between eplerenone and amlodipine shows that both treatments decrease systolic blood pressure to a similar extent but eplerenone is better tolerated. In conclusion, there is now evidence that eplerenone can play an important role in the treatment of mild to moderate arterial

  6. A cohort evaluation on arterial stiffness and hypertensive disorders in pregnancy

    PubMed Central

    2012-01-01

    Background Hypertensive disorders in pregnancy are associated with systemic endothelial dysfunction leading to impaired physiological vasodilation. Recent evidence has shown central aortic pressures obtained through pulse wave analysis, at less than 14 weeks of gestation, to be predictive of pre-eclampsia. In light of this, we aimed to evaluate the role of central aortic stiffness in the prediction and discrimination of hypertensive disorders in pregnancy. Methods A cohort study of women with viable, singleton pregnancies at less than 14 weeks of amenorrhoea, and without multiple pregnancies, autoimmune or renal disease, diagnosed with aneuploidy or fetal anomaly will be recruited from a single maternity hospital and followed up till delivery and puerperium. A targeted sample size of 1000 eligible pregnant women will be enrolled into the study from antenatal clinics. Main exposure under study is central aortic pulse pressure using radial pulse wave recording, and the outcomes under follow-up are gestational hypertension and pre-eclampsia. Other measures include lifestyle factors such as smoking, physical exercise, psyc