Pulmonary vasculature

2017 ◽  
Author(s):  
Sophie Vergnaud ◽  
David Dobarro ◽  
John Wort
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Treatment Strategies ◽  
Symptomatic Improvement ◽  
Pulmonary Vasculature ◽  
History Of ◽  
Diffuse Cutaneous Systemic Sclerosis ◽  
Pulmonary Arterial ◽  
Phosphodiesterase 5 ◽  
Haemodynamic Improvement

A 16-year-old girl with a diagnosis of diffuse cutaneous systemic sclerosis is referred to a specialist pulmonary hypertension centre with a history of progressive breathlessness, reduced exercise tolerance, and raised pulmonary pressures on transthoracic echocardiogram. She is found to have pulmonary arterial hypertension on right cardiac catheterization and is started on sildenafil, a phosphodiesterase-5 inhibitor, which stabilizes her condition. An endothelin receptor antagonist is added, which provides some initial symptomatic improvement. She continues to deteriorate over a period of 5 years, ultimately requiring intravenous prostanoids, the only treatment to provide a real symptomatic and haemodynamic improvement. This chapter explores the physiology and pathophysiology of pulmonary arterial hypertension, its classification, the means of investigation and diagnosis, who to refer to specialist centres, and the concepts behind current and future treatment strategies.

scholarly journals Identification of the Novel Variants in Patients With Chronic Thromboembolic Pulmonary Hypertension

2020 ◽  
Vol 9 (21) ◽  
Author(s):  
Nobuhiro Yaoita ◽  
Kimio Satoh ◽  
Taijyu Satoh ◽  
Toru Shimizu ◽  
Sakae Saito ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Vasculature ◽  
Nonsynonymous Variant ◽  
Whole Exome ◽  
Thromboembolic Pulmonary Hypertension ◽  
History Of ◽  
Pulmonary Arterial

Background Although chronic thromboembolic pulmonary hypertension (CTEPH) and acute pulmonary embolism (APE) share some clinical manifestations, a limited proportion of patients with CTEPH have a history of APE. Moreover, in histopathologic studies, it has been revealed that pulmonary vasculature lesions similar to pulmonary arterial hypertension existed in patients with CTEPH. Thus, it remains unknown whether these 3 disorders also share genetic backgrounds. Methods and Results Whole exome screening was performed with DNA isolated from 51 unrelated patients with CTEPH of Japanese ancestry. The frequency of genetic variants associated with pulmonary arterial hypertension or APE in patients with CTEPH was compared with those in the integrative Japanese Genome Variation Database 3.5KJPN. Whole exome screening analysis showed 17 049 nonsynonymous variants in patients with CTEPH. Although we found 6 nonsynonymous variants that are associated with APE in patients with CTEPH, there was no nonsynonymous variant associated with pulmonary arterial hypertension. Patients with CTEPH with a history of APE had nonsynonymous variants of F5 , which encodes factor V. In contrast, patients with CTEPH without a history of APE had a nonsynonymous variant of THBD , which encodes thrombomodulin. Moreover, thrombin‐activatable fibrinolysis inhibitor, which is one of the pathogenic proteins in CTEPH, was significantly more activated in those who had the variants of THBD compared with those without it. Conclusions These results provide the first evidence that patients with CTEPH have some variants associated with APE, regardless of the presence or absence of a history of APE. Furthermore, the variants might be different between patients with CTEPH with and without a history of APE.

scholarly journals Pulmonary arterial hypertension in patients treated with interferon

2014 ◽  
Vol 44 (6) ◽  
pp. 1627-1634 ◽  
Author(s):  
Laurent Savale ◽  
Caroline Sattler ◽  
Sven Günther ◽  
David Montani ◽  
Marie-Camille Chaumais ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Case Control Study ◽  
Severe Pulmonary Hypertension ◽  
Reference Centre ◽  
History Of ◽  
Ifn Therapy ◽  
Pulmonary Arterial ◽  
Haemodynamic Improvement ◽  
Control Study

Isolated cases of pulmonary arterial hypertension (PAH) in patients treated with interferon (IFN) α or β have been reported in the literature.The aim of this study was to describe all consecutive cases of PAH patients with a history of IFN exposure identified in the French reference centre for severe pulmonary hypertension between 1998 and 2012.A total of 53 patients with PAH and a history of IFN therapy were identified. 48 patients had been treated with IFNα for chronic hepatitis C. Most of them had portal hypertension (85%) and 56% had HIV co-infection. Five additional patients had been treated with IFNβ for multiple sclerosis. The diagnosis of PAH was made within 3 years after IFN therapy in 66% of patients. Repeated haemodynamic assessment was available in 13 out of 16 patients exposed to IFN after the diagnosis of PAH. Increased pulmonary vascular resistance >20% was observed in 11 out of 13 cases (median 43% increase; IQR 32–67%). In five of these patients, IFN withdrawal resulted in spontaneous haemodynamic improvement.This retrospective analysis suggests that IFN therapy may trigger PAH. However, most of these patients had other risk factors for PAH. A prospective case–control study is necessary to definitively establish a link between IFN exposure and PAH.

scholarly journals Repetitive and Brief Occlusion of Total Right Atrium Venous Blood Flow Improves Experimental Pulmonary Arterial Hypertension: a novel potential therapeutic strategy

2020 ◽  
Author(s):  
Nan Liu ◽  
Ying Xing ◽  
Chen Wang
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Therapeutic Strategy ◽  
Superior Vena ◽  
Venous Blood ◽  
Vena Cava ◽  
Vegf Receptor ◽  
Venous Blood Flow ◽  
History Of ◽  
Pulmonary Arterial

AbstractPulmonary arterial hypertension (PAH) is a vascular disorder associated with significant morbidity and mortality. The pathophysiology of PAH remains controversial, but the only currently available therapies for PAH are pharmacological pulmonary artery vasodilation, decreasing right ventricular (RV) afterload, and relieving symptoms. By now, there is no therapy being able to minimize vascular remodeling processes and thus to reverse or delay the natural history of the disease. It has been generally thought that reduction of RV preload was detrimental, which deteriorated the systemic hemodynamics. In the present study, however, we repetitively and briefly occluded (RBO) both superior vena cava and inferior vena cava by ligation (occlusion for less than 5 seconds then re-open for 30 seconds and repeated 5 cycles as one sequence, 1 sequence every 6 hours) to intermittently restrict RV preload, for continuous 24 hours, total 5 sequences, in the Sugen 5416 (VEGF receptor blocker) and hypoxia induced PAH rat models and we found this strategy was beneficial for lowering pulmonary vascular resistance (PVR).

scholarly journals Managing the Patient With Pulmonary Arterial Hypertension and Methamphetamine Use: A Practical Perspective for the Clinician

2018 ◽  
Vol 17 (2) ◽  
pp. 55-62 ◽  
Author(s):  
Nimaljeet Tarango ◽  
Andrea Gergay Baird
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
San Francisco ◽  
Medical Center ◽  
The United States ◽  
Methamphetamine Abuse ◽  
Methamphetamine Use ◽  
Personal Experiences ◽  
History Of ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a serious, chronic, progressive cardiopulmonary disease. PAH is associated with several concomitant conditions, as well as drugs and toxins.12 Methamphetamine abuse is likely associated with the development of PAH.3 Methamphetamine abuse is epidemic in the United States and abroad, with rates of new users escalating since 2012. There are over 100,000 new users annually as young as 12 years old. Treating a patient with a history of methamphetamine abuse poses many challenges for a clinician, including nonadherence, therapeutic treatment selection, complex psychosocial issues, and relapse or continued drug abuse. Patients with methamphetamine-associated PAH (Meth-APAH) have higher mortality rates when compared to idiopathic PAH.3 Having a better understanding of the complexities of addiction and working with a multidisciplinary team that includes a social worker to provide care and counseling to these patients can improve their trajectory. In this article, we will offer insight and background into methamphetamine abuse and addiction, as well as discuss a practical approach for clinicians in treating a patient with Meth-APAH, based on the literature, as well as our personal experiences at University of California, San Francisco Medical Center.

Abstract 18587: Downregulation of Pulmonary Artery Endothelial Catechol-o-methyltransferase Activity by Aldosterone Increases Norepinephrine Levels in Pulmonary Arterial Hypertension

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Samantha Torquato ◽  
Kiyotake Ishikawa ◽  
Jaume Aguerro ◽  
Bradley A Maron ◽  
Joseph Loscalzo ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Right Heart Failure ◽  
Therapeutic Interventions ◽  
Pulmonary Vasculature ◽  
Methyltransferase Activity ◽  
Comt Activity ◽  
Pulmonary Arterial

Elevated levels of norepinephrine (NE) occur in pulmonary arterial hypertension (PAH) and are determined, in part, by the activity of catechol- O -methyltransferase (COMT). COMT degrades catecholamines, is negatively regulated by calcium, and is expressed by pulmonary artery endothelial cells (PAEC). As hyperaldosteronism occurs in PAH and aldosterone (ALDO) influences calcium levels, we hypothesized that ALDO decreases COMT activity to increase NE levels in PAH. Accordingly, human PAEC were treated with ALDO (10 -7 mol/L), a level that is achieved clinically in PAH, for up to 72 h. Compared to vehicle-treated PAEC, ALDO decreased COMT activity by 59.2 ± 6.2% (p<0.01) to increase NE levels in the medium (122.4 ± 11.8 vs. 210.7 ± 15.5 pg/mL/mg protein, p<0.01). This occurred as a result of an ALDO-mediated decrease in COMT protein expression by 52.6 ± 9.3% (p<0.01) as well as an increase in intracellular calcium levels (102.9 ± 21.0 vs. 167.7 ± 17.8 nmol/L, p<0.05) to inhibit activity. These effects were abrogated by coincubation with spironolactone. To determine the in vivo relevance of these findings, COMT was examined in the rat monocrotaline model of PAH with confirmed hyperALDO. COMT was decreased (47.6 ± 10.2 %control, p<0.05) in remodeled pulmonary arterioles with a concomitant increase in lung NE levels (432.8 ± 44.5 vs. 899.7 ± 34.2 pg/mL, p<0.01) compared to control rats. In the porcine pulmonary vein banding model of pulmonary hypertension (PH-pigs) with elevated mean pulmonary artery pressure (15[13-15] vs. 35[27-43], p<0.01) and pulmonary vascular resistance (PVR) index (1.97[1.74-2.28] vs. 5.78[2.61-8.75], p <0.05), ALDO levels were also increased (27.1 ± 5.1 vs. 60.8 ± 10.6 pg/mL, p<0.03) in advance of right heart failure as compared to sham controls. PH-pigs demonstrated a 48.3 ± 9.9% (p<0.02) decrease in pulmonary vascular COMT expression and an increase in NE levels (114.6 ± 20.2 vs. 1,622.6 ± 489.2 pg/mL, p<0.02) that correlated positively with ALDO levels (R 2 =0.58, p<0.02). These findings were confirmed in patients with PAH. Together, these data indicate that there is crosstalk in the pulmonary vasculature between ALDO and the sympathetic nervous system to regulate NE levels in PAH, and thus, have implications for therapeutic interventions.

Abstract 382: Cyclophilin A (CypA) is a Pathogenic Mediator of Pulmonary Arterial Hypertension

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Chao Xue
Keyword(s):  
Oxidative Stress ◽  
Smooth Muscle ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Specific Inhibitor ◽  
Cyclophilin A ◽  
Pulmonary Vasculature ◽  
Tunel Staining ◽  
Mesenchymal Transition ◽  
Pulmonary Arterial

Rationale: Pulmonary arterial hypertension (PAH) is a devastating disease in which oxidative stress has been proposed to mediate pathological changes to the pulmonary vasculature such as endothelial cell (EC) apoptosis, endothelial to mesenchymal transition (EndMT), vascular smooth muscle cell (VSMC) proliferation, and inflammation. Our previous study showed that cyclophilin A (CypA) was secreted from EC and VSMC in response to oxidative stress, and much of the secreted CypA was acetylated (AcK-CypA). Furthermore, CypA was increased in the plasma of patients with PAH. Objective: To evaluate the cell- s pecific role of CypA in PAH and compare the relative effects of AcK-CypA and CypA on EC apoptosis, development of an inflammatory EC phenotype and EndMT. Methods and Results: Transgenic overexpression of CypA in EC, but not SMC, caused a PAH phenotype including increased pulmonary artery pressure, α-smooth muscle actin expression in small arteries, and CD45 positive cells in the lungs. Mechanistic analysis using cultured mouse lung microvascular EC showed that CypA and AcK-CypA increased apoptosis measured by caspase 3 cleavage and TUNEL staining. MM284, a specific inhibitor of extracellular CypA, prevented EC apoptosis. In addition, CypA and AcK-CypA promoted an EC inflammatory phenotype assessed by increased VCAM1 and ICAM1 expression, phosphorylation of p65, and degradation of IkB. Furthermore, CypA and AcK-CypA promoted EndMT assayed by change in cell morphology, increased mesenchymal markers and EndMT related transcription factors. At all concentrations, AcK-CypA stimulated greater increases in apoptosis, inflammation and EndMT than CypA. Conclusions: EC-derived CypA (especially AcK-CypA) causes PAH by a presumptive mechanism involving increased EC apoptosis, inflammation and EndMT. Our results suggest that inhibiting extracellular secreted CypA is a novel therapeutic approach for PAH.

Sign in / Sign up

Export Citation Format

Share Document