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https://www.readbyqxmd.com/read/27929408/a-review-of-targeted-pulmonary-arterial-hypertension-specific-pharmacotherapy
#1
REVIEW
Ali Ataya, Jessica Cope, Hassan Alnuaimat
Significant advances in the understanding of the pathophysiology of pulmonary arterial hypertension over the past two decades have led to the development of targeted therapies and improved patient outcomes. Currently, a broad armamentarium of pulmonary arterial hypertension-specific drugs exists to assist in the treatment of this complex disease state. In this manuscript, we provide a comprehensive review of the current Food and Drug Administration (FDA)-approved pulmonary arterial hypertension-specific therapies, and their supporting evidence for adults, targeting the nitric oxide, soluble guanylate cyclase, endothelin, and prostacyclin pathways...
December 6, 2016: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/27926661/the-effect-of-intraoperative-and-6-h-postoperative-intravenous-administration-of-low-dose-prostacyclin-on-the-endothelium-hemostasis-and-hemodynamics-in-patients-undergoing-a-pancreaticoduodenoctemy-a-randomized-controlled-pilot-study
#2
Pär I Johansson, Christian R Mortensen, Tatiana Nielsen, Carsten Tollund, Jakob Stensballe, Carsten P Hansen, Hans J Frederiksen, Sisse R Ostrowski
BACKGROUND: Capillary leakage, secondary to endothelial breakdown, is common in patients undergoing major surgical procedures with extensive tissue injury and this is associated with increased morbidity and mortality. Prostacyclin has been ascribed cytoprotective properties together with its vasodilatory and antiplatelet effects. The present pilot study investigated the safety and endothelial protective effects of low-dose prostacyclin infusion. PATIENTS AND METHODS: A randomized placebo-controlled pilot study evaluating the effect of prostacyclin (iloprost) infusion (1...
December 6, 2016: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27919660/a-comparison-of-vasodilation-mode-among-selexipag-ns-304-2-4-5-6-diphenylpyrazin-2-yl-isopropyl-amino-butoxy-n-methylsulfonyl-acetamide-its-active-metabolite-mre-269-and-various-prostacyclin-receptor-agonists-in-rat-porcine-and-human-pulmonary-arteries
#3
Chiaki Fuchikami, Kohji Murakami, Koyuki Tajima, Junko Homan, Keiji Kosugi, Kazuya Kuramoto, Michiko Oka, Keiichi Kuwano
Selexipag (NS-304; [2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N- (methylsulfonyl)acetamide]) is a novel, orally available non-prostanoid prostacyclin receptor (IP receptor) agonist that has recently been approved for the treatment of pulmonary arterial hypertension (PAH). We examined the effect of the active metabolite of selexipag, MRE-269, and IP receptor agonists that are currently available as PAH therapeutic drugs on the relaxation of rat, porcine and human pulmonary artery. cAMP formation in human pulmonary artery smooth muscle cells was induced by all test compounds (MRE-269, epoprostenol, iloprost, treprostinil and beraprost sodium) and suppressed by IP receptor antagonists (CAY10441 and 2-[4-(1H-indol-4-yloxymethyl)-benzyloxycarbonylamino]-3-phenyl-propionic acid)...
December 2, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27916240/spatial-phenotyping-of-the-endocardial-endothelium-as-a-function-of-intracardiac-hemodynamic-shear-stress
#4
Margaret E McCormick, Elisabetta Manduchi, Walter R T Witschey, Robert C Gorman, Joseph H Gorman, Yi-Zhou Jiang, Christian J Stoeckert, Alex J Barker, Samuel Yoon, Michael Markl, Peter F Davies
Despite substantial evidence for the central role of hemodynamic shear stress in the functional integrity of vascular endothelial cells, hemodynamic and molecular regulation of the endocardial endothelium lining the heart chambers remains understudied. We propose that regional differences in intracardiac hemodynamics influence differential endocardial gene expression leading to phenotypic heterogeneity of this cell layer. Measurement of intracardiac hemodynamics was performed using 4-dimensional flow MRI in healthy humans (n=8) and pigs (n=5)...
November 16, 2016: Journal of Biomechanics
https://www.readbyqxmd.com/read/27916219/coupling-factor-6-is-upregulated-in-monocrotaline-induced-pulmonary-arterial-hypertension-in-rats
#5
Nannan Li, Jie Yin, Weidong Cai, Jingjing Liu, Na Zhang, Suhua Yan, Lucheng Song, Xiaolu Li
BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare and fatal disease. The prostacyclin (PGI2) pathway is a well-known therapeutic target for PAH. As a novel vasoconstrictive peptide, coupling factor 6 (CF6) has been recognized as the only endogenous inhibitor of PGI2. However, the relationship between CF6 and PAH is still unknown. In this study, we investigated the involvement of CF6 in PAH in rats. METHODS: A total of 80 Sprague-Dawley rats were randomly divided into 2 groups: a control group (with saline intraperitoneally) and a monocrotaline (MCT)-treated group (with MCT 60mg/kg intraperitoneal injection)...
December 2016: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/27915453/effects-of-chronic-nitric-oxide-synthase-inhibition-on-v-o2max-and-exercise-capacity-in-mice
#6
M Wojewoda, K Przyborowski, B Sitek, A Zakrzewska, L Mateuszuk, J A Zoladz, S Chlopicki
Acute inhibition of NOS by L-NAME (N(ω)-nitro-L-arginine methyl ester) is known to decrease maximal oxygen consumption (V'O2max) and impair maximal exercise capacity, whereas the effects of chronic L-NAME treatment on V'O2max and exercise performance have not been studied so far. In this study, we analysed the effect of L-NAME treatment, (LN2 and LN12, respectively) on V'O2max and exercise capacity (in maximal incremental running and prolonged sub-maximal incremental running tests), systemic NO bioavailability (plasma nitrite (NO2(-)) and nitrate (NO3(-))) and prostacyclin (PGI2) production in C57BL6/J mice...
December 3, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27914476/lidocaine-relaxation-in-isolated-rat-aortic-rings-is-enhanced-by-endothelial-removal-possible-role-of-kv-katp-channels-and-a2a-receptor-crosstalk
#7
Aryadi Arsyad, Geoffrey P Dobson
BACKGROUND: Lidocaine is an approved local anesthetic and Class 1B antiarrhythmic with a number of ancillary properties. Our aim was to investigate lidocaine's vasoreactivity properties in intact versus denuded rat thoracic aortic rings, and the effect of inhibitors of nitric oxide (NO), prostenoids, voltage-dependent Kv and KATP channels, membrane Na(+)/K(+) pump, and A2a and A2b receptors. METHODS: Aortic rings were harvested from adult male Sprague Dawley rats and equilibrated in an organ bath containing oxygenated, modified Krebs-Henseleit solution, pH 7...
December 3, 2016: BMC Anesthesiology
https://www.readbyqxmd.com/read/27903664/practical-considerations-for-therapies-targeting-the-prostacyclin-pathway
#8
REVIEW
Harrison W Farber, Wendy Gin-Sing
Therapies that target the prostacyclin pathway play a key role in the treatment of both early- and late-stage pulmonary arterial hypertension, and provide significant clinical benefits for patients. A number of agents have been approved, which are administered via intravenous, subcutaneous, inhaled or oral routes. The use of these therapies is associated with practical challenges, relating to the need for up-titration and their routes of administration. We discuss here a number of measures that can be taken to support patients and healthcare professionals in order to address the complexities of using these therapies and to encourage compliance...
December 2016: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/27903663/beyond-a-single-pathway-combination-therapy-in-pulmonary-arterial-hypertension
#9
REVIEW
Olivier Sitbon, Sean Gaine
There is a strong rationale for combining therapies to simultaneously target three of the key pathways implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Evidence to support this strategy is growing, and a number of studies have demonstrated that combination therapy, administered as either a sequential or an initial regimen, can improve long-term outcomes in PAH. Dual combination therapy with a phosphodiesterase-5 inhibitor and an endothelin receptor antagonist is the most widely utilised combination regimen...
December 2016: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/27898216/characterization-of-prostacyclin-associated-leg-pain-in-patients-with-pulmonary-arterial-hypertension
#10
Gabriel L Pagani-Estévez, Keith M Swetz, Michael D McGoon, Robert P Frantz, Susan K Tointon, Ann M Karnyski, Louise A Durst, James C Watson
RATIONALE: Prostacyclin-associated leg pain is a potentially debilitating adverse effect of prostacyclin therapy for patients with pulmonary arterial hypertension (PAH). However, to our knowledge, this entity has not been systematically studied. OBJECTIVE: To characterize the clinical features and metabolic risk factors for prostacyclinassociated leg pain. METHODS: At one academic medical center we assembled and analyzed a case series of patients with PAH and prostacyclin-associated leg pain...
November 29, 2016: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/27895464/selexipag-in-the-treatment-of-pulmonary-arterial-hypertension-design-development-and-therapy
#11
REVIEW
Elizabeth Ashley Hardin, Kelly M Chin
Pulmonary arterial hypertension is characterized by abnormalities in the small pulmonary arteries including increased vasoconstriction, vascular remodeling, proliferation of smooth muscle cells, and in situ thrombosis. Selexipag, a novel, oral prostacyclin receptor agonist, has been shown to improve hemodynamics in a phase II clinical trial and reduce clinical worsening in a large phase III clinical trial involving patients with pulmonary arterial hypertension. In this paper, we describe the prostacyclin signaling pathway, currently available oral prostanoid medications, and the development and clinical use of selexipag...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27885399/absolute-oral-bioavailability-of-selexipag-a-novel-oral-prostacyclin-ip-receptor-agonist
#12
Priska Kaufmann, Noémie Hurst, Béatrice Astruc, Jasper Dingemanse
PURPOSE: The aim of this single-center, open-label study was to assess the absolute bioavailability of an oral (tablet) versus intravenous (i.v.) formulation of selexipag in healthy subjects. METHODS: A pilot phase in three healthy male subjects, which preceded the main study, consisted of a single 20-minute i.v. infusion of 50 μg selexipag. Its objectives were to ensure the safety of the i.v. formulation and to select the i.v. dose for the main study. The main study had a randomized, two-way crossover design in 16 healthy male subjects...
November 24, 2016: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27852936/the-vasorelaxant-mechanisms-of-methanol-on-isolated-rat-aortic-rings-involvement-of-ion-channels-and-signal-transduction-pathways
#13
Y Bai, Q Zhang, Z Yang, Z Meng, Q Zhao
It is reported that methanol is generally used as an industrial solvent, antifreeze, windshield washer fluid, cooking fuel and perfume. Methanol ingestion can lead to severe metabolic disturbances, blindness, or even death. So far, few studies about its negative effects on cardiovascular system have been reported. The purpose of this study was to determine the vasoactive effect of methanol and roles of ion channels and signal transduction pathways on isolated rat aorta. The results suggested that the mechanism of methanol-induced vasorelaxation at low concentrations (<500 mM) was mediated by ATP-sensitive K(+) (KATP) and L-type Ca(2+) channels, but the mechanism at high concentrations (>600 mM) was related to KATP, voltage-dependent K(+), big-conductance Ca(2+)-activated K(+), L-type Ca(2+) channels as well as prostacyclin, protein kinase C, β-adrenoceptors pathways...
November 16, 2016: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/27834752/cyclooxygenase-2-derived-prostaglandins-mediate-cerebral-microcirculation-in-a-juvenile-ischemic-rat-model
#14
Pierre-Louis Leger, Julien Pansiot, Valerie Besson, Bruno Palmier, Sylvain Renolleau, Olivier Baud, Bruno Cauli, Christiane Charriaut-Marlangue
BACKGROUND AND PURPOSE: We previously showed that the selective neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI) increases cerebral microcirculation in a juvenile ischemic rat model. We address the roles of cyclooxygenase (COX)-elaborated prostaglandins in collateral recruitment and blood supply. METHODS: Fourteen-day-old rats were subjected to ischemia-reperfusion and treated with either PBS or 7-NI (25 mg/kg) at the reperfusion onset. Six-keto-prostaglandin F1α was measured using ELISA...
December 2016: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/27802898/oxymatrine-attenuated-isoproterenol-induced-heart-failure-in-rats-via-regulation-of-cox-2-pgi2-pathway
#15
Ru Zhou, Qingbin Xu, Yehua Xu, Aiqin Xiong, Yang Wang, Ping Ma
Oxymatrine (OMT) is an active constituent of traditional Chinese herb Sophora japonica Ait which has been shown to exert potent anti-inflammatory,anti-oxidant and anti-fibrosis properties. Our previous studies have demonstrated that OMT has protective effects on isoproterenol-induced heart failure in rats through regulation of DDAH/ADMA metabolism pathway.In this study,we further investigated whether OMT could attenuate isoproterenol-induced heart failure through the regulation of COX-2/PGI2 pathway. Heart failure was induced in Sprague-Dawley rats by 5mg/kg isoproterenol subcutaneous injection for 7days...
October 29, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27800456/successful-lung-transplant-after-prolonged-extracorporeal-membrane-oxygenation-ecmo-in-a-child-with-pulmonary-hypertension-a-case-report
#16
Cecile Tissot, Walid Habre, Paola Soccal, Maja Isabel Hug, Dominique Bettex, Michel Pellegrini, Yacine Aggoun, Anne Mornand, Afksendyios Kalangos, Peter Rimensberger, Maurice Beghetti
INTRODUCTION: The use of extracorporeal membrane oxygenation (ECMO) is considered a risk factor for, or even a potential contraindication to, lung transplantation. However, only a few pediatric cases have been described thus far. CASE PRESENTATION: A 9-year-old boy with idiopathic pulmonary arterial hypertension developed cardiac arrest after the insertion of a central catheter. ECMO was used as a bridge to lung transplantation. However, after prolonged resuscitation, he developed medullary ischemia and medullary syndrome...
August 2016: Research in Cardiovascular Medicine
https://www.readbyqxmd.com/read/27800004/attenuation-of-thrombosis-by-crude-rice-oryza-sativa-bran-policosanol-extract-ex-vivo-platelet-aggregation-and-serum-levels-of-arachidonic-acid-metabolites
#17
Wai-Teng Wong, Maznah Ismail, Eusni Rahayu Mohd Tohit, Rasedee Abdullah, Yi-Da Zhang
Background. Vascular occlusion or thrombosis was often attributed to uncontrolled platelet activation. Influence of sugarcane policosanol extract on platelet was reported but little was known of rice bran policosanol, particularly its mechanisms of actions on platelet activities. Objective. Antiplatelet mechanisms of rice bran policosanol extract (RBE) were studied using hyperlipidemic Sprague Dawley rats. Ex vivo platelet aggregation, platelet count (PC), bleeding time (BT), and coagulation time were assayed...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27787407/vasodilators-in-septic-shock-resuscitation-a-clinical-perspective
#18
Thiago Domingos Corrêa, Roberto Rabello Filho, Murillo Santucci Cesar Assunção, Eliézer Silva, Alexandre Lima
Microcirculatory abnormalities have been shown to be frequent in patients with septic shock despite "normalization" of systemic hemodynamics. Several studies have explored the impact of vasodilator therapy (prostacyclin, inhaled nitric oxide, topic acetylcholine and nitroglycerin) on microcirculation and tissue perfusion, with contradictory findings.In this narrative review, we briefly present the pathophysiological aspects of microcirculatory dysfunction, and depict the evidence supporting the use of vasodilators and other therapeutic interventions (fluid administration, blood transfusion, vasopressors and dobutamine) aiming to improve the microcirculatory flow in septic shock patients...
October 26, 2016: Shock
https://www.readbyqxmd.com/read/27783213/a-prospective-randomized-study-of-inhaled-prostacyclin-versus-nitric-oxide-in-patients-with-residual-pulmonary-hypertension-after-pulmonary-endarterectomy
#19
Shinichiro Abe, Keiichi Ishida, Masahisa Masuda, Hideki Ueda, Hiroki Kohno, Kaoru Matsuura, Yusaku Tamura, Michiko Watanabe, Goro Matsumiya
OBJECTIVES: Pulmonary endarterectomy (PEA) is an effective treatment for chronic thromboembolic pulmonary hypertension (CTEPH), but postoperative residual hypertension leads to in-hospital mortality. Inhaled epoprostenol sodium (PGI2) and NO are administered for pulmonary hypertension after cardiothoracic surgery. This prospective study provides the first comparative evaluation of the effects of inhaled PGI2 and NO on pulmonary hemodynamics, systemic hemodynamics, and gas exchange in patients developing residual pulmonary hypertension after PEA...
October 25, 2016: General Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/27771466/gender-related-differences-in-pulmonary-arterial-hypertension-targeted-drugs-administration
#20
REVIEW
Alberto M Marra, Nicola Benjamin, Christina Eichstaedt, Andrea Salzano, Michele Arcopinto, Luna Gargani, Michele D Alto, Paola Argiento, Lorenzo Falsetti, Paolo Di Giosia, Andrea M Isidori, Francesco Ferrara, Eduardo Bossone, Antonio Cittadini, Ekkehard Grünig
During the last 15 years, a real "paradigm-shift" occurred, due to the development of PAH-targeted drugs, leading to crucial improvements in symptoms, exercise capacity, hemodynamics and outcome of PAH patients. In order to describe differences regarding epidemiology and therapy in PAH according to gender, we performed a review of the available literature in "PubMed" and "Web of Science" databases. In order to find relevant articles, we combined each of the following the keywords "pulmonary arterial hypertension", "gender", "sex", "men", "woman", "male", "female", "phosphodiesterase inhibitors", "endothelin receptor antagonists", "prostanoids"...
October 19, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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