scholarly journals The Biological Bases of Group 2 Pulmonary Hypertension

2019 ◽  
Vol 20 (23) ◽  
pp. 5884 ◽  
Author(s):  
Ana I. Fernández ◽  
Raquel Yotti ◽  
Ana González-Mansilla ◽  
Teresa Mombiela ◽  
Enrique Gutiérrez-Ibanes ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Current Knowledge ◽  
Molecular Genetic ◽  
Pressure Overload ◽  
Pulmonary Vasculature ◽  
World Population ◽  
Pulmonary Hemodynamics ◽  
Ongoing Research ◽  
Therapeutic Implications ◽  
Group 2

Pulmonary hypertension (PH) is a potentially fatal condition with a prevalence of around 1% in the world population and most commonly caused by left heart disease (PH-LHD). Usually, in PH-LHD, the increase of pulmonary pressure is only conditioned by the retrograde transmission of the left atrial pressure. However, in some cases, the long-term retrograde pressure overload may trigger complex and irreversible biomechanical and biological changes in the pulmonary vasculature. This latter clinical entity, designated as combined pre- and post-capillary PH, is associated with very poor outcomes. The underlying mechanisms of this progression are poorly understood, and most of the current knowledge comes from the field of Group 1-PAH. Treatment is also an unsolved issue in patients with PH-LHD. Targeting the molecular pathways that regulate pulmonary hemodynamics and vascular remodeling has provided excellent results in other forms of PH but has a neutral or detrimental result in patients with PH-LHD. Therefore, a deep and comprehensive biological characterization of PH-LHD is essential to improve the diagnostic and prognostic evaluation of patients and, eventually, identify new therapeutic targets. Ongoing research is aimed at identify candidate genes, variants, non-coding RNAs, and other biomarkers with potential diagnostic and therapeutic implications. In this review, we discuss the state-of-the-art cellular, molecular, genetic, and epigenetic mechanisms potentially involved in PH-LHD. Signaling and effective pathways are particularly emphasized, as well as the current knowledge on -omic biomarkers. Our final aim is to provide readers with the biological foundations on which to ground both clinical and pre-clinical research in the field of PH-LHD.

Transient severe isolated right ventricular hypertrophy in neonates

2003 ◽  
Vol 13 (4) ◽  
pp. 384-386 ◽  
Author(s):  
Munesh Tomar ◽  
Sitaraman Radhakrishnan ◽  
Savitri Shrivastava
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Ventricular Function ◽  
Ventricular Hypertrophy ◽  
Pressure Overload ◽  
Posterior Wall ◽  
Right Ventricular Hypertrophy ◽  
Pulmonary Vasculature ◽  
Normal Thickness ◽  
The Right

We report two instances of transient isolated right-sided myocardial hypertrophy in patients with an intact ventricular septum, normal thickness of the posterior wall of the left ventricle, and normal ventricular function, diagnosed by echocardiography on the third day of life. The two neonates, born at 36 and 38 weeks gestation respectively, had perinatal distress. Both were diagnosed as having isolated right ventricular hypertrophy with mild pulmonary hypertension, which disappeared in both cases within 8 weeks without any specific therapy. Though the cause of the ventricular hypertrophy remains unclear, we believe that it is the consequence of remodeling of pulmonary vasculature secondary to acute perinatal distress, resulting in persistent pulmonary hypertension and producing pressure overload on the right ventricle, and hence right ventricular hypertrophy. The finding of early and transient right ventricular hypertrophy, with normal left-sided structures and normal ventricular function, has thus far failed to gain attention in the paediatric cardiologic literature.

scholarly journals The incremental shuttle walk test predicts mortality in non-group 1 pulmonary hypertension: results from the ASPIRE Registry

2019 ◽  
Vol 9 (2) ◽  
pp. 204589401984864 ◽  
Author(s):  
Catherine G. Billings ◽  
Robert Lewis ◽  
Judith A. Hurdman ◽  
Robin Condliffe ◽  
Charlie A. Elliot ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Ceiling Effect ◽  
Walk Test ◽  
Limited Information ◽  
Pulmonary Hemodynamics ◽  
Disease Etiology ◽  
Invasive Test ◽  
Group 2 ◽  
Test Distance ◽  
Group 1

Pulmonary hypertension (PH) is classified into five groups based on disease etiology but there is only limited information on the prognostic value of exercise testing in non-group 1 PH. In group 1 PH, the incremental shuttle walking test (ISWT) distance has been shown to correlate with pulmonary hemodynamics and predict survival without a ceiling effect. This study assessed the ISWT in non-group 1 PH. Data were retrieved from the ASPIRE Registry (Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre) for consecutive patients diagnosed with PH. Patients were required to have been systematically assessed as group 2–5 PH and to have a baseline ISWT within three months of cardiac catheterization. Patients were stratified according to incremental shuttle walk test distance (ISWD) and ISWT distance percent predicted (ISWD%pred). A total of 479 patients with non-group 1 PH were identified. ISWD and ISWD%pred correlated significantly with symptoms and hemodynamic severity. ISWD and ISWD%pred predicted survival with no ceiling effect. The test was prognostic in groups 2, 3, and 4. ISWD and ISWD%pred and change in ISWD and ISWD%pred at one year were all significant predictors of outcome. In patients with non-group 1 PH the ISWT is a simple non-invasive test that is easy to perform, is predictive of survival at baseline and follow-up, reflects change, and can be used in the assessment of PH of any etiology.

scholarly journals Pulmonary Hypertension and Obesity: Focus on Adiponectin

2019 ◽  
Vol 20 (4) ◽  
pp. 912 ◽  
Author(s):  
Fabio Perrotta ◽  
Ersilia Nigro ◽  
Mariano Mollica ◽  
Adriano Costigliola ◽  
Vito D’Agnano ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Biological Effects ◽  
Strong Association ◽  
Hypoglycemic Agents ◽  
Pulmonary Vasculature ◽  
No Production ◽  
Peroxisome Proliferator ◽  
Pulmonary Hemodynamics

Pulmonary hypertension is an umbrella term including many different disorders causing an increase of the mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg. Recent data revealed a strong association between obesity and pulmonary hypertension. Adiponectin is a protein synthetized by the adipose tissue with pleiotropic effects on inflammation and cell proliferation, with a potential protective role on the pulmonary vasculature. Both in vivo and in vitro studies documented that adiponectin is an endogenous modulator of NO production and interferes with AMP-activated protein kinase (AMPK) activation, mammalian target of rapamycin (mTOR), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ) signaling preventing endothelial dysfunction and proliferation. Furthermore, adiponectin ameliorates insulin resistance by mediating the biological effects of peroxisome proliferator-activated receptor-gamma (PPARγ). Therefore, adiponectin modulation emerged as a theoretical target for the treatment of pulmonary hypertension, currently under investigation. Recently, consistent data showed that hypoglycemic agents targeting PPARγ as well as renin–angiotensin system inhibitors and mineralocorticoid receptor blockers may influence pulmonary hemodynamics in different models of pulmonary hypertension.

scholarly journals Chronic thromboembolic pulmonary hypertension – still evolving

2020 ◽  
Vol 2020 (1) ◽  
Author(s):  
Mario Gerges ◽  
Magdi Yacoub
Keyword(s):  
Pulmonary Hypertension ◽  
Medical Therapy ◽  
Treatment Options ◽  
Pulmonary Arteries ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Right Heart Failure ◽  
Pulmonary Vasculature ◽  
Pulmonary Hemodynamics ◽  
Thromboembolic Pulmonary Hypertension ◽  
Multiple Treatments

Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the leading causes of severe pulmonary hypertension (PH). The disease is still underdiagnosed, and the true prevalence is unknown. CTEPH is characterized by intraluminal non-resolving thrombus organization and fibrous stenosis, or complete obliteration of pulmonary arteries, promoted by progressive remodeling of the pulmonary vasculature. One consequence of this is an increase in pulmonary vascular resistance and pressure, resulting in PH and progressive right heart failure, leading to death if left untreated.Endovascular disobliteration by pulmonary endarterectomy (PEA) is the preferred treatment for CTEPH patients. PEA surgery is the only technique that can potentially cure CTEPH disease, especially in patients with fresh or organized thrombi of the proximal branches of pulmonary arteries. However, not all patients are eligible for PEA surgery. Recent research has provided evidence suggesting balloon pulmonary angioplasty (BPA) and targeted medical therapy as additional promising available treatments options for inoperable CTEPH and recurrent/persistent PH after PEA surgery.Studies on BPA have shown it to improve pulmonary hemodynamics, symptoms, exercise capacity and RV function in inoperable CTEPH. Subsequently, BPA has developed into an essential component of the modern era of CTEPH treatment. Large randomized controlled trials have demonstrated varying significant improvements with targeted medical therapy in technically inoperable CTEPH patients. Thus, treatment of CTEPH requires a comprehensive multidisciplinary assessment, including an experienced PEA surgeon, PH specialist, BPA interventionist and CTEPH-trained radiologist at expert centers. In this comprehensive review, we address the latest developments in the fast-evolving field of CTEPH. These include advancements in imaging modalities and developments in operative and interventional techniques, which have widened the range of patients who may benefit from these procedures. The efficacy and safety of targeted medical therapies in CTEPH patients are also discussed. As the treatment options for CTEPH improve, hybrid management involving multiple treatments in the same patient may become a viable option in the near future.

Prostacyclin and milrinone by aerosolization improve pulmonary hemodynamics in newborn lambs with experimental pulmonary hypertension

2010 ◽  
Vol 109 (3) ◽  
pp. 677-684 ◽  
Author(s):  
Vasanth H. Kumar ◽  
Daniel D. Swartz ◽  
Nasir Rashid ◽  
Satyan Lakshminrusimha ◽  
Changxing Ma ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Vasculature ◽  
Duration Of Action ◽  
Pulmonary Hemodynamics ◽  
Pulmonary Vasodilation ◽  
Pulmonary Arterial ◽  
Near Term ◽  
Phosphodiesterase Type ◽  
Type 3 ◽  
Phosphodiesterase Type 3

Aerosolized prostacyclin (PGI2) produces selective pulmonary vasodilation in patients with pulmonary hypertension (PH). The response to PGI2 may be increased by phosphodiesterase type 3 inhibitors such as milrinone. We studied the dose response effects of aerosolized PGI2 and aerosolized milrinone both alone and in combination on pulmonary and systemic hemodynamics in newborn lambs with Nω-nitro-l-arginine methyl ester (l-NAME)-induced PH. We hypothesized that coaerosolization of PGI2 with milrinone would additively decrease pulmonary vascular resistance (PVR), prolong the duration of action of PGI2, and selectively dilate the pulmonary vasculature. Near-term lambs were delivered by C-section and instrumented and PH was induced by l-NAME (bolus 25 mg/kg; infusion 10 mg·kg−1·h−1) and indomethacin. In the first set of experiments, PGI2 was aerosolized at random doses of 2, 20, 100, 200, 500, and 1,000 ng·kg−1·min−1 followed by milrinone at doses of 0.1, 1, and 10 μg·kg−1·min−1 over 10 min. In the second set of experiments, milrinone at 1 μg·kg−1·min−1 was aerosolized in combination with PGI2 at doses of 20, 100, and 200 ng·kg−1·min−1 over 10 min. Pulmonary arterial pressures (PAP) and PVR decreased significantly with increasing doses of aerosolized PGI2 and milrinone. The combination of PGI2 and milrinone significantly reduced PAP and PVR more than either of the drugs aerosolized alone. Addition of milrinone significantly increased the duration of action of PGI2. When aerosolized independently, PGI2 and milrinone selectively dilated the pulmonary vasculature but the combination did not. Milrinone enhances the vasodilatory effects of PGI2 on the pulmonary vasculature but caution must be exercised regarding systemic hypotension.

Clinical Trials Update

2013 ◽  
Vol 12 (3) ◽  
pp. 118-118
Author(s):  
Fernando Torres
Keyword(s):  
Clinical Trials ◽  
Pulmonary Hypertension ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Ventricular Systolic Dysfunction ◽  
Ongoing Research

The Clinical Trials Update highlights new and ongoing research trials that are evaluating therapies for PAH. In this issue, Fernando Torres, MD, examines a study on patients with pulmonary hypertension associated with left ventricular systolic dysfunction.

Plant Compounds for the Treatment of Diabetes, a Metabolic Disorder: NF-κB as a Therapeutic Target

2020 ◽  
Vol 26 (39) ◽  
pp. 4955-4969
Author(s):  
Ravi Sahukari ◽  
Jyothi Punabaka ◽  
Shanmugam Bhasha ◽  
Venkata S. Ganjikunta ◽  
Shanmugam K. Ramudu ◽  
...  
Keyword(s):  
Diabetic Complications ◽  
Current Knowledge ◽  
World Population ◽  
Future Studies ◽  
Expression Of Genes ◽  
Treatment Of Diabetes ◽  
Online Library ◽  
And Oxidative Stress ◽  
Stress Activation ◽  
Plant Compounds

Background: The prevalence of diabetes in the world population hás reached 8.8 % and is expected to rise to 10.4% by 2040. Hence, there is an urgent need for the discovery of drugs against therapeutic targets to sojourn its prevalence. Previous studies proved that NF-κB serves as a central agent in the development of diabetic complications. Objectives: This review intended to list the natural plant compounds that would act as inhibitors of NF-κB signalling in different organs under the diabetic condition with their possible mechanism of action. Methods: Information on NF-κB, diabetes, natural products, and relation in between them, was gathered from scientific literature databases such as Pubmed, Medline, Google scholar, Science Direct, Springer, Wiley online library. Results and Conclusion: NF-κB plays a crucial role in the development of diabetic complications because of its link in the expression of genes that are responsible for organs damage such as kidney, brain, eye, liver, heart, muscle, endothelium, adipose tissue and pancreas by inflammation, apoptosis and oxidative stress. Activation of PPAR-α, SIRT3/1, and FXR through many cascades by plant compounds such as terpenoids, iridoids, flavonoids, alkaloids, phenols, tannins, carbohydrates, and phytocannabinoids recovers diabetic complications. These compounds also exhibit the prevention of NF-κB translocation into the nucleus by inhibiting NF-κB activators, such as VEGFR, RAGE and TLR4 receptors, which in turn, prevent the activation of many genes involved in tissue damage. Current knowledge on the treatment of diabetes by targeting NF-κB is limited, so future studies would enlighten accordingly.

scholarly journals Unique Aspects of the Developing Lung Circulation: Structural Development and Regulation of Vasomotor Tone

2016 ◽  
Vol 6 (4) ◽  
pp. 407-425 ◽  
Author(s):  
Yuangsheng Gao ◽  
David N. Cornfield ◽  
Kurt R. Stenmark ◽  
Bernard Thébaud ◽  
Steven H. Abman ◽  
...  
Keyword(s):  
Lung Development ◽  
Lung Diseases ◽  
Vascular Tone ◽  
Current Knowledge ◽  
Normal Lung ◽  
Pulmonary Vasculature ◽  
Structural Development ◽  
Vasomotor Tone ◽  
Disease States ◽  
Vasculogenesis And Angiogenesis

This review summarizes our current knowledge on lung vasculogenesis and angiogenesis during normal lung development and the regulation of fetal and postnatal pulmonary vascular tone. In comparison to that of the adult, the pulmonary circulation of the fetus and newborn displays many unique characteristics. Moreover, altered development of pulmonary vasculature plays a more prominent role in compromised pulmonary vasoreactivity than in the adult. Clinically, a better understanding of the developmental changes in pulmonary vasculature and vasomotor tone and the mechanisms that are disrupted in disease states can lead to the development of new therapies for lung diseases characterized by impaired alveolar structure and pulmonary hypertension.

4971Blood viscosity and its relevance to the diagnosis and management of pulmonary hypertension: a new elephant in the cathlab

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Kempny ◽  
K Dimopoulos ◽  
A E Fraisse ◽  
G P Diller ◽  
L C Price ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Cardiac Catheterization ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Significant Difference ◽  
The Difference ◽  
Clinically Significant ◽  
The Relationship

Abstract Background Pulmonary vascular resistance (PVR) is an essential parameter assessed during cardiac catheterization. It is used to confirm pulmonary vascular disease, to assess response to targeted pulmonary hypertension (PH) therapy and to determine the possibility of surgery, such as closure of intra-cardiac shunt or transplantation. While PVR is believed to mainly reflect the properties of the pulmonary vasculature, it is also related to blood viscosity (BV). Objectives We aimed to assess the relationship between measured (mPVR) and viscosity-corrected PVR (cPVR) and its impact on clinical decision-making. Methods We assessed consecutive PH patients undergoing cardiac catheterization. BV was assessed using the Hutton method. Results We included 465 patients (56.6% female, median age 63y). The difference between mPVR and cPVR was highest in patients with abnormal Hb levels (anemic patients: 5.6 [3.4–8.0] vs 7.8Wood Units (WU) [5.1–11.9], P<0.001; patients with raised Hb: 10.8 [6.9–15.4] vs. 7.6WU [4.6–10.8], P<0.001, respectively). Overall, 33.3% patients had a clinically significant (>2.0WU) difference between mPVR and cPVR, and this was more pronounced in those with anemia (52.9%) or raised Hb (77.6%). In patients in the upper quartile for this difference, mPVR and cPVR differed by 4.0WU [3.4–5.2]. Adjustment of PVR required Conclusions We report, herewith, a clinically significant difference between mPVR and cPVR in a third of contemporary patients assessed for PH. This difference is most pronounced in patients with anemia, in whom mPVR significantly underestimates PVR, whereas in most patients with raised Hb, mPVR overestimates it. Our data suggest that routine adjustment for BV is necessary.

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