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Pulmonary arterial hypertension

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https://www.readbyqxmd.com/read/27932789/the-maintenance-ability-and-ca-2-availability-of-skeletal-muscle-are-enhanced-by-sildenafil
#1
Mei Huang, Keon Jin Lee, Kyung-Jin Kim, Mi Kyoung Ahn, Chung-Hyun Cho, Do Han Kim, Eun Hui Lee
Sildenafil relaxes vascular smooth muscle cells and is used to treat pulmonary artery hypertension as well as erectile dysfunction. However, the effectiveness of sildenafil on skeletal muscle and the benefit of its clinical use have been controversial, and most studies focus primarily on tissues and organs from disease models without cellular examination. Here, the effects of sildenafil on skeletal muscle at the cellular level were examined using mouse primary skeletal myoblasts (the proliferative form of skeletal muscle stem cells) and myotubes, along with single-cell Ca(2+) imaging experiments and cellular and biochemical studies...
December 9, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27932471/a-paradigm-shift-is-needed-in-the-field-of-pulmonary-arterial-hypertension-for-its-entrance-into-the-precision-medicine-era
#2
Vikram Gurtu, Evangelos D Michelakis
No abstract text is available yet for this article.
December 9, 2016: Circulation Research
https://www.readbyqxmd.com/read/27932335/multicentre-randomised-placebo-controlled-trial-of-oral-anticoagulation-with-apixaban-in-systemic-sclerosis-related-pulmonary-arterial-hypertension-the-sphinx-study-protocol
#3
Alicia Calderone, Wendy Stevens, David Prior, Harshal Nandurkar, Eli Gabbay, Susanna M Proudman, Trevor Williams, David Celermajer, Joanne Sahhar, Peter K K Wong, Vivek Thakkar, Nathan Dwyer, Jeremy Wrobel, Weng Chin, Danny Liew, Margaret Staples, Rachelle Buchbinder, Mandana Nikpour
INTRODUCTION: Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12-15% of patients with SSc and accounts for 30-40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH...
December 8, 2016: BMJ Open
https://www.readbyqxmd.com/read/27931609/clinical-and-biological-insights-into-combined-post-and-pre-capillary-pulmonary-hypertension
#4
Tufik R Assad, Anna R Hemnes, Emma K Larkin, Andrew M Glazer, Meng Xu, Quinn S Wells, Eric H Farber-Eger, Quanhu Sheng, Yu Shyr, Frank E Harrell, John H Newman, Evan L Brittain
BACKGROUND: Pulmonary hypertension (PH) is a common and morbid complication of left heart disease with 2 subtypes: isolated post-capillary pulmonary hypertension (Ipc-PH) and combined post-capillary and pre-capillary pulmonary hypertension (Cpc-PH). Little is known about the clinical or physiological characteristics that distinguish these 2 subphenotypes or if Cpc-PH shares molecular similarities to pulmonary arterial hypertension (PAH). OBJECTIVES: The goal of this study was to test the hypothesis that the hemodynamic and genetic profile of Cpc-PH would more closely resemble PAH than Ipc-PH...
December 13, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27931011/cardiac-dysfunction-of-pulmonary-artery-aneurysm-in-patients-with-pulmonary-arterial-hypertension
#5
Konomi Sakata, Toru Satoh, Aoi Isaka, Yoichiro Uesugi, Mitsufumi Furuya, Kenichi Matsushita, Hideaki Yoshino
BACKGROUND: Pulmonary artery aneurysm (PAA) occurs in some patients with pulmonary arterial hypertension (PAH). We evaluated the characteristics of cardiac dysfunction in patients with PAH complicated by PAA. METHODS: Echocardiography and right-heart catheterization were performed in 130 PAH patients to measure the maximum dimensions of the main pulmonary artery (MPA) trunk and evaluate right ventricular (RV) and left ventricular (LV) function. RESULTS: A diameter of >40mm was defined as PAA in the MPA trunk...
October 29, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27929408/a-review-of-targeted-pulmonary-arterial-hypertension-specific-pharmacotherapy
#6
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/27927914/tryptophan-hydroxylase-1-tph1-inhibition-impacts-pulmonary-vascular-remodeling-in-two-rat-models-of-pulmonary-hypertension
#7
Robert J Aiello, Patricia-Ann Bourassa, Qing Zhang, Jeffrey Dubins, Daniel R Goldberg, Stephane De Lombaert, Marc Humbert, Christophe Guignabert, Maria A Cavasin, Timothy A McKinsey, Vishwas Paralkar
Pulmonary arterial hypertension (PAH) is a progressive disease defined by a chronic elevation in pulmonary arterial pressure with extensive pulmonary vascular remodeling and perivascular inflammation characterized by an accumulation of macrophages, lymphocytes, dendritic cells and mast cells. While the exact etiology of the disease is unknown, clinical as well as pre-clinical data strongly implicate a role for serotonin (5 HT) in the process. Here, we investigated the chronic effects of pharmacological inhibition of tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme in peripheral 5 HT biosynthesis, in two pre-clinical models of pulmonary hypertension (PH), the monocrotaline (MCT) rat and the SU5416 (SUGEN)-hypoxia rat...
December 7, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27927014/genetic-modification-of-the-lung-directed-toward-treatment-of-human-disease
#8
Dolan Sondhi, Katie Stiles, Bishnu P De, Ronald G Crystal
Genetic modification therapy is a promising therapeutic strategy for many diseases of the lung intractable to other treatments. Lung gene therapy has been the subject of numerous preclinical animal experiments and human clinical trials, for targets including genetic diseases such as cystic fibrosis and α1-antitrypsin deficiency, complex disorders such as asthma, allergy and lung cancer, infections such as respiratory syncytial virus and Pseudomonas, as well as pulmonary arterial hypertension, transplant rejection and lung injury...
December 7, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27925430/pulmonary-hypertension-as-estimated-by-doppler-echocardiography-in-adolescent-and-adult-patients-with-cystic-fibrosis-and-their-relationship-with-clinical-lung-function-and-sleep-findings
#9
Bruna Ziegler, Christiano Perin, Fernanda Cano Casarotto, Simone Chaves Fagondes, Sérgio Saldanha Menna-Barreto, Paulo de Tarso Roth Dalcin
BACKGROUND: In cystic fibrosis (CF) patients, end stage of pulmonary disease is characterized by pulmonary hypertension (PH), hypoxemia, decrease in exercise tolerance and sleep quality. OBJECTIVE: To evaluate the association between clinical, lung function, sleep quality and polysomnographic variables with PH in CF patients aged 16 years or older. METHODS: In a cross-sectional study, 51 clinically stable CF patients underwent a clinical evaluation, an overnight polysomnography and answered sleep questionnaires (Pittsburgh Sleep Quality Index - PSQI and Epworth sleepiness scale - ESS)...
December 7, 2016: Clinical Respiratory Journal
https://www.readbyqxmd.com/read/27925228/a-mock-circulatory-system-incorporating-a-compliant-3d-printed-anatomical-model-to-investigate-pulmonary-hemodynamics
#10
Paul G M Knoops, Giovanni Biglino, Alun D Hughes, Kim H Parker, Linzhang Xu, Silvia Schievano, Ryo Torii
A realistic mock circulatory system (MCS) could be a valuable in vitro testbed to study human circulatory hemodynamics. The objective of this study was to design a MCS replicating the pulmonary arterial circulation, incorporating an anatomically representative arterial model suitable for testing clinically relevant scenarios. A second objective of the study was to ensure the system's compatibility with magnetic resonance imaging (MRI) for additional measurements. A latex pulmonary arterial model with two generations of bifurcations was manufactured starting from a 3D-printed mold reconstructed from patient data...
December 7, 2016: Artificial Organs
https://www.readbyqxmd.com/read/27922752/abnormal-glucose-metabolism-and-high-energy-expenditure-in-idiopathic-pulmonary-arterial-hypertension
#11
Gustavo A Heresi, Steven K Malin, Jarrod W Barnes, Liping Tian, John P Kirwan, Raed A Dweik
RATIONALE: Insulin resistance has emerged as a potential mechanism related to the pathogenesis of idiopathic pulmonary arterial hypertension (IPAH). However, direct measurements of insulin and glucose metabolism have not been performed in IPAH patients to date. OBJECTIVES: To perform comprehensive metabolic phenotyping on humans with IPAH. METHODS: We assessed plasma insulin and glucose using an oral glucose tolerance test and estimated insulin resistance and beta-cell function in 14 IPAH patients and 14 controls matched for age, sex, blood pressure, and body mass index (BMI),...
December 6, 2016: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/27920514/usefulness-of-the-6-minute-walk-test-as-a-screening-test-for-pulmonary-arterial-enlargement-in-copd
#12
Yutaro Oki, Masahiro Kaneko, Yukari Fujimoto, Hideki Sakai, Shogo Misu, Yuji Mitani, Takumi Yamaguchi, Hisafumi Yasuda, Akira Ishikawa
PURPOSE: Pulmonary hypertension and exercise-induced oxygen desaturation (EID) influence acute exacerbation of COPD. Computed tomography (CT)-detected pulmonary artery (PA) enlargement is independently associated with acute COPD exacerbations. Associations between PA to aorta (PA:A) ratio and EID in patients with COPD have not been reported. We hypothesized that the PA:A ratio correlated with EID and that results of the 6-minute walk test (6MWT) would be useful for predicting the risk associated with PA:A >1...
2016: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/27919930/mir-17-20-controls-prolyl-hydroxylase-2-phd2-hypoxia-inducible-factor-1-hif1-to-regulate-pulmonary-artery-smooth-muscle-cell-proliferation
#13
Tianji Chen, Qiyuan Zhou, Haiyang Tang, Melike Bozkanat, Jason X-J Yuan, J Usha Raj, Guofei Zhou
BACKGROUND: Previously we found that smooth muscle cell (SMC)-specific knockout of miR-17~92 attenuates hypoxia-induced pulmonary hypertension. However, the mechanism underlying miR-17~92-mediated pulmonary artery SMC (PASMC) proliferation remains unclear. We sought to investigate whether miR-17~92 regulates hypoxia-inducible factor (HIF) activity and PASMC proliferation via prolyl hydroxylases (PHDs). METHODS AND RESULTS: We show that hypoxic sm-17~92(-/-) mice have decreased hematocrit, red blood cell counts, and hemoglobin contents...
December 5, 2016: Journal of the American Heart Association
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
#14
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/27919209/evaluation-of-echocardiographic-abnormalities-in-hiv-positive-patients-treated-with-antiretroviral-medications
#15
Sina Moradmand Badie, Mehrnaz Rasoulinejad, Mohammadreza Salehi, Hamid Emadi Kochak, SeyedAhmad SeyedAlinaghi, Seyed Ali Dehghan Manshadi, Fatemeh Jahanjo Amin Abad, Banafsheh Moradmand Badie
BACKGROUND: Echocardiography is a reliable means for the diagnosis of functional and valvular diseases of the heart in HIV positive and HIV negative patients. The current study was to evaluate echocardiographic abnormalities in HIV positive patients under an antiretroviral therapy (ART) program in Tehran, Imam Khomeini Hospital, Iran. METHODS: This is a descriptive cross-sectional study, conducted among 231 HIV positive patients under ART. All HIV positive patients including 150 men (65%) and 81 women (35%) (mean age of 41 years) were assessed by trans-thoracic echocardiography (TTE) in Imam Khomeini Hospital, over the period from 2013 to 2014...
December 5, 2016: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/27916219/coupling-factor-6-is-upregulated-in-monocrotaline-induced-pulmonary-arterial-hypertension-in-rats
#16
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/27916210/heart-type-fatty-acid-binding-protein-in-the-assessment-of-acute-pulmonary-embolism
#17
Hai-Yan Qian, Ji Huang, Yue-Jin Yang, Yan-Min Yang, Zhi-Zhong Li, Jing-Mei Zhang
OBJECTIVE: To explore the predictive value of heart-type fatty acid binding protein (H-FABP) in the stratification and prognosis of patients with acute pulmonary embolism (APE). METHODS: According to risk stratification, 69 patients with APE admitted into the emergency department within 24 hours after onset were divided into the following 3 groups: high-risk group, moderate-risk group and low-risk group. H-FABP- and cardiac troponin I (cTNI)-positive rates of all groups were analyzed and compared, and the correlation between major adverse events (death, endotracheal intubation and cardiopulmonary resuscitation) and the cardiac markers (heart rate, arterial partial pressure of oxygen, right ventricular dimension, pulmonary arterial pressure, etc...
December 2016: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/27914611/restoration-of-uridine-5-triphosphate-suppressed-delayed-rectifying-k-currents-by-an-no-activator-kmup-1-involves-rhoa-rho-kinase-signaling-in-pulmonary-artery-smooth-muscle-cells
#18
Zen-Kong Dai, Chang-Ling Kao, Su-Ling Hsieh, Ing-Jun Chen, Bin-Nan Wu
We have demonstrated that KMUP-1 (7-[2-[4-(2-chlorobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) blunts monocrotaline-induced pulmonary arterial hypertension by altering Ca(2+) sensitivity, K(+)-channel function, endothelial nitric oxide synthase activity, and RhoA/Rho kinase (ROCK) expression. This study further investigated whether KMUP-1 impedes uridine 5'-triphosphate (UTP)-inhibited delayed rectifying K(+) (KDR) current in rat pulmonary arteries involved the RhoA/ROCK signaling. Pulmonary artery smooth muscle cells (PASMCs) were enzymatically dissociated from rat pulmonary arteries...
December 2016: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/27913427/intermittent-hypoxia-during-recovery-from-neonatal-hyperoxic-lung-injury-causes-long-term-impairment-of-alveolar-development-a-new-rat-model-of-bpd
#19
Anastasiya Mankouski, Crystal Kantores, Mathew J Wong, Julijana Ivanovska, Amish Jain, Eric J Benner, Stanley N Mason, A Keith Tanswell, Richard L Auten, Robert P Jankov
Bronchopulmonary dysplasia (BPD) is a chronic lung injury characterized by impaired alveologenesis that may persist into adulthood. Rat models of BPD using varying degrees of hyperoxia to produce injury either cause early mortality or spontaneously recover following removal of the inciting stimulus, thus limiting clinical relevance. We sought to refine an established rat model induced by exposure to 60% O2 from birth by following hyperoxia with intermittent hypoxia (IH). Rats exposed from birth to air or 60% O2 until day 14 were recovered in air with or without IH (FiO2 = 0...
December 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27913300/suppression-of-nadph-oxidase-attenuates-hypoxia-induced-dysfunctions-of-endothelial-progenitor-cells
#20
Bin Liu, Kai-Di Ren, Jing-Jie Peng, Tao Li, Xiu-Ju Luo, Chengming Fan, Jin-Fu Yang, Jun Peng
NADPH oxidases (NOX) - derived reactive oxygen species (ROS) contribute to oxidative injury in hypoxia-induced pulmonary arterial hypertension. This study aims to evaluate the status of NOX in endothelial progenitor cells (EPCs) under hypoxic condition and to determine whether NOX inhibitors could attenuate hypoxia-induced dysfunctions of EPCs. EPCs were isolated from peripheral blood of SD rats and subjected to hypoxia (O2/N2/CO2, 1/94/5) for 24 h. The cells were collected for β-galactosidase or Hoechst staining, or for functional analysis (migration, adhesion and tube formation)...
November 29, 2016: Biochemical and Biophysical Research Communications
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