scholarly journals Pulmonary Artery Endovascular Device Compensates for Loss of Vascular Compliance in Pulmonary Arterial Hypertension

2020 ◽  
Vol 76 (19) ◽  
pp. 2284-2286
Author(s):  
Christian Gerges ◽  
Karl Vollmers ◽  
Marc R. Pritzker ◽  
John Gainor ◽  
John Scandurra ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Vascular Compliance ◽  
Pulmonary Arterial ◽  
Endovascular Device

scholarly journals Prognostic impact of neurohormonal inhibition in pulmonary arterial hypertension

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Scagliola ◽  
I Rota ◽  
M Cheli ◽  
C Brunelli ◽  
M Balbi ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Beta Blocker ◽  
Diastolic Pressure ◽  
Smoking Habit ◽  
Prognostic Impact ◽  
Mineralocorticoid Receptor Antagonist ◽  
Kaplan Meier ◽  
Pulmonary Arterial

Abstract Background Experimental evidence points towards a hyperactivity of the sympathetic nervous system and renin-angiotensin-aldosterone system in the pathobiology of pulmonary arterial hypertension (PAH), raising the hypothesis that blockade of neurohormonal axis may have favorable effects in this context. Purpose To assess the use and prognostic impact of neurohormonal inhibitors (NEUi) in a single centre cohort of subjects with PAH. Methods We analysed retrospectively collected data from our register of right heart catheterizations (RHC) performed consecutively from January 1st 2005 until October 31st 2018. We selected patients with PAH and complete information about demographics, biochemical data and drug therapy at the time of RHC. Patients on beta-blocker, angiotensin-converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB) or mineralocorticoid receptor antagonist (MRA) at the time of RHC were classified as NEUi users. Comparisons between NEUi recipients and non-recipients were drawn by chi-square or t-test, as appropriate. Death from any cause was assessed by Kaplan-Meier analysis. Results Complete data were available for 57 PAH patients. Mean pulmonary artery pressure, pulmonary artery wedge pressure, diastolic pressure gradient, pulmonary vascular resistance and cardiac index were 45.0±14.9 mmHg, 10.9±3.5 mmHg, 16.0±10.2 mmHg, 8.8±5.1 Wood units and 2.5±0.8 l/min/m2 respectively. Twenty-seven subjects (47.4%) were taking at least one NEUi when RHC was performed: 12 (21.1%) were on beta-blocker, 15 (26.3%) on ACEi/ARB and 6 (10.5%) on MRA. NEUi users were significantly older (67.6±11.9 vs. 58.3±15.2 years, p=0.039), had a higher body mass index (25.9±4.4 vs. 23.6±3.5, p=0.029), more frequently systemic arterial hypertension (74.1% vs. 40.0%, p=0.020), smoking habit (51.9% vs. 20.0%, p=0.025) and lower estimated glomerular filtration rate (58.7±22.7 vs. 73.7±24.7 ml/min/1.73 m2, p=0.022) than non-users. Moreover, 5 NEUi users (18.5%), but no NEUi non-users, had a history of coronary artery disease. Hemodynamic parameters were similar in NEUi recipients and non-recipients (p=NS). Seven patients (25.9%) died in the NEUi users group vs. 17 (56.7%) in the non-users one (p=0.038). Kaplan-Meier analysis confirmed that subjects not taking NEUi were more likely to die over the course of follow-up (Log-Rank p=0.020) (Figure 1). Conclusions Our data identify a subset of atypical PAH patients, with pre-capillary pulmonary hypertension and a comorbidity profile for left heart disease (LHD), in whom NEUi have shown to improve survival. A prognostic benefit of NEUi, due to their effects on cardiovascular comorbidities in this kind of patients, has been speculated. Future prospective studies are needed to identify the most appropriate treatment strategies for atypical forms of PAH, with subtle and probably covert LHD. Figure 1. Kaplan-Meier survival curves Funding Acknowledgement Type of funding source: None

Beta3-adrenergic stimulation restores endothelial mitochondrial dynamics and prevents pulmonary arterial hypertension

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Oliver ◽  
S.F Rocha ◽  
M Spaczynska ◽  
D.V Lalama ◽  
M Gomez ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Therapeutic Strategy ◽  
Mitochondrial Dynamics ◽  
Systolic Pressure ◽  
Funding Source ◽  
Pulmonary Arterial

Abstract Background Endothelial dysfunction is one of the most important hallmarks of pulmonary arterial hypertension (PAH). This leads to anomalous production of vasoactive mediators that are responsible for a higher vascular tone and a subsequent increase in pulmonary artery pressure (PAP), and to an increased vascular permeability that favors perivascular inflammation and remodeling, thus worsening the disease. Therefore, preservation of the endothelial barrier could become a relevant therapeutic strategy. Purpose In previous studies, others and we have suggested the pharmacological activation of the β3-adrenergic receptor (AR) as a potential therapeutic strategy for pulmonary hypertension (PH) due to left heart disease. However, its potential use in other forms of PH remain unclear. The aim of the present study was to elucidate whether the β3-AR agonist mirabegron could preserve pulmonary endothelium function and be a potential new therapy in PAH. Methods For this purpose, we have evaluated the effect of mirabegron (2 and 10 mg/kg·day) in different animal models, including the monocrotaline and the hypoxia-induced PAH models in rats and mice, respectively. Additionally, we have used a transgenic mouse model with endothelial overexpression of human β3-AR in a knockout background, and performed in vitro experiments with human pulmonary artery endothelial cells (HPAECs) for mechanistic experiments. Results Our results show a dose dependent effect of mirabegron in reducing mean PAP and Right Ventricular Systolic Pressure in both mice and rats. In addition, the use of transgenic mice has allowed us to determine that pulmonary endothelial cells are key mediators of the beneficial role of β3-AR pathway in ameliorating PAH. Mechanistically, we have shown in vitro that activation of β3-AR with mirabegron protects HPAECs from hypoxia-induced ROS production and mitochondrial fragmentation by restoring mitochondrial fission/fusion dynamics. Conclusions This protective effect of mirabegron would lead to endothelium integrity and preserved pulmonary endothelial function, which are necessary for a correct vasodilation, avoiding increased permeability and remodeling. Altogether, the current study demonstrates a beneficial effect of the β3-AR agonist mirabegron that could open new therapeutic avenues in PAH. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Programa de Atracciόn de Talento, Comunidad de Madrid

Safflower injection inhibits pulmonary arterial remodeling in a monocrotaline-induced pulmonary arterial hypertension rat model

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Aifeng Chen ◽  
Shibiao Ding ◽  
Liangliang Kong ◽  
Jianpu Xu ◽  
Fei He ◽  
...  
Keyword(s):  
Growth Factor ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Cardiac Muscle ◽  
Rat Model ◽  
Dependent Manner ◽  
Arterial Remodeling ◽  
Pulmonary Arterial ◽  
Dose Dependent

AbstractPulmonary arterial hypertension (PAH) is a group of diseases with an increase of pulmonary artery pressure (PAP) and pulmonary vascular resistance. Here, the effects of safflower injection, a preparation of Chinese herbs, was investigated in a monocrotaline (MCT)-induced PAH rat model. PAP, carotid artery pressure (CAP), and the right ventricular hypertrophy index (RVHI) increased in the PAH group, while safflower injection was able to inhibit this increase to similar levels as observed in the normal group. The arteriole wall of the lungs and cardiac muscle were thickened and edema was observed in the PAH group, while these pathologies were improved in the herb-treated group in a dose-dependent manner. MCT treatment induced proliferation of pulmonary artery smooth muscle cells (PASMCs), which was inhibited by safflower injection in a dose-dependent manner. Our experimental results demonstrated that safflower injection can regulate pulmonary arterial remodeling through affecting the expression of connective tissue growth factor, transforming growth factor-β, integrin, collagen or fibronectin, which subsequently affected the thicknesses of the arteriole walls of the lungs and cardiac muscle, and thereby benefits the control of PAH. This means safflower injection improved the abnormalities in PAP, CAP and RVHI, and pulmonary arterial remodeling through regulation of remodeling factors.

Abstract 532: New Agonist of A2a Receptor Reduces Ventricular and Vascular Dysfunction in Monocrotaline-induced Pulmonary Arterial Hypertension in Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Allan K Alencar ◽  
Sharlene L Pereira ◽  
Arthur E Kummerle ◽  
Sharon S Langraf ◽  
Celso Caruso-Neves ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Vascular Reactivity ◽  
Vascular Dysfunction ◽  
Systolic Pressure ◽  
Pulmonary Tissue ◽  
A2a Receptor ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is characterized by enhanced pulmonary vascular resistance with subsequent remodeling and right ventricular hypertrophy. Vascular reactivity and ventricular function were investigated in rats with monocrotaline-induced PAH and treated with a new N-acylhydrazone derivative named as LASSBio-1359. METHODS: Protocols were approved by Animal Care and Use Committee at Universidade Federal do Rio de Janeiro. Male Wistar rats received a single i.p. injection of monocrotaline (MCT) (60 mg/kg) for PAH induction and were randomly divided in groups which were treated with: saline, vehicle and LASSBio-1359 (50 mg/kg p.o.). After 14 days of treatment, some parameters were evaluated: pulmonary acceleration time (PAT); right ventricular systolic pressure (RVSP); vascular reactivity to acetylcholine; expression of iNOS in pulmonary tissue; wall thickness of pulmonary artery (PAWT). Results: PAT (ms) was increased from 26.2 ± 2.8 to 41.3 ± 3.9 in PAH group treated with vehicle (n=8, p<0.05) and was reduced to 24.2 ± 1.7 when PAH group was treated with LASSBio-1359. RVSP (mmHg) increased from 26.0 ± 2.0 to 55.2 ± 2.3 in PAH group (p<0.05) but was similar to control after treatment with LASSBio-1359 (31.8 ± 2.3 mm Hg). Ratio of right ventricle and body weight (mg/g) was 0.66 ± 0.02, 1.63 ± 0.16 and 0.87 ± 0.10 for control, vehicle- and LASSBio-1359-treated PAH groups, respectively. PAH promoted ventricular dysfunction which was reduced by LASSBio-1359. The pulmonary artery maximum relaxation (%) was 57.3 ± 5.5, 43.6 ± 1.2 and 61.4 ± 8.4 for control, vehicle and LASSBio-1359-treated groups indicating that PAH promoted endothelium injury which was recovered by LASSBio-1359. iNOS expression in pulmonary tissue was increased from 0.48 ± 1.31 to 0.98 ± 3.14 in PAH group and reduced to 0.53 ± 1.83 in rats treated with LASSBio-1359. The PAWT (%) were increased from 74.1 ± 1.3 to 90.2 ± 2.7 in PAH group (p<0.05) but was 74.4 ± 1.3 when treated with LASSBio-1359. This compound showed an in vitro vasodilatory activity mediated by activation of adenosinergic A2A receptor. Conclusion: LASSBio-1359 reduced ventricular and vascular dysfunction in monocrotaline-induced PAH in rats indicating a possible new alternative to treat PAH.

Enhanced Pulmonary Artery Radiodensity in Pulmonary Arterial Hypertension: A Sign of Early Calcification?

2019 ◽  
Vol 199 (6) ◽  
pp. 799-802 ◽  
Author(s):  
Virginie F. Tanguay ◽  
Camille Babin ◽  
Gabrielle Giardetti ◽  
Catherine Sohier-Poirier ◽  
Vincent Ménard-Cholette ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Pulmonary Arterial

scholarly journals Traditional Herbal Medicine Discovery for the Treatment and Prevention of Pulmonary Arterial Hypertension

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhifeng Xue ◽  
Yixuan Li ◽  
Mengen Zhou ◽  
Zhidong Liu ◽  
Guanwei Fan ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Herbal Medicine ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Premature Death ◽  
Right Heart Failure ◽  
Tanshinone Iia ◽  
Active Components ◽  
Traditional Herbal Medicine ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is characterized by pulmonary artery remodeling that may subsequently culminate in right heart failure and premature death. Although there are currently both non-pharmacological (lung transplantation, etc.) and pharmacological (Sildenafil, Bosentan, and new oral drugs on trial) therapies available, PAH remains a serious and fatal pulmonary disease. As a unique medical treatment, traditional herbal medicine (THM) treatment has gradually exerted its advantages in treating PAH worldwide through a multi-level and multi-target approach. Additionally, the potential mechanisms of THM were deciphered, including suppression of proliferation and apoptosis of pulmonary artery smooth muscle cells, controlling the processes of inflammation and oxidative stress, and regulating vasoconstriction and ion channels. In this review, the effects and mechanisms of the frequently studied compound THM, single herbal preparations, and multiple active components from THM are comprehensively summarized, as well as their related mechanisms on several classical preclinical PAH models. It is worth mentioning that sodium tanshinone IIA sulfonate sodium and tetramethylpyrazine are under clinical trials and are considered the most promoting medicines for PAH treatment. Last, reverse pharmacology, a strategy to discover THM or THM-derived components, has also been proposed here for PAH. This review discusses the current state of THM, their working mechanisms against PAH, and prospects of reverse pharmacology, which are expected to facilitate the natural anti-PAH medicine discovery and development and its bench-to-bedside transformation.

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