Hypoxia Mediates Mutual Repression between microRNA-27a and PPARγ in the Pulmonary Vasculature

Pulmonary arterial hypertension is a progressive disease of the pulmonary vasculature, ultimately leading to right heart failure and death. Current treatment is aimed at targeting three different pathways: the prostacyclin, endothelin and nitric oxide pathways. These therapies improve functional class, increase exercise capacity and improve haemodynamics. In addition, data from a meta-analysis provide compelling evidence of improved survival. Despite these treatments, the outcome is still grim and the cause of death is inevitable – right ventricular failure. One explanation for this paradox of haemodynamic benefit and still worse outcome is that the right ventricle does not benefit from a modest reduction in pulmonary vascular resistance. This article describes the physiological concepts that might underlie this paradox. Based on these concepts, we argue that not only a significant reduction in pulmonary vascular resistance, but also a significant reduction in pulmonary artery pressure is required to save the right ventricle. Haemodynamic data from clinical trials hold the promise that these haemodynamic requirements might be met if upfront combination therapy is used.

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A Mathematical Model for the Study of Hemorrhagic Shock and Fluid Resuscitation: The Systemic and Pulmonary Vasculature

10.21236/ada266292 ◽

1993 ◽

Author(s):

Tammy J. Doherty

Keyword(s):

Mathematical Model ◽

Hemorrhagic Shock ◽

Fluid Resuscitation ◽

Pulmonary Vasculature

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G420(P) A case series on abnormal pulmonary vasculature

10.1136/archdischild-2019-rcpch.405 ◽

2019 ◽

Author(s):

M Ranjan ◽

V Cheruvalli ◽

S Hamad

Keyword(s):

Case Series ◽

Pulmonary Vasculature

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

Pulmonary Circulation ◽

10.1086/688890 ◽

2016 ◽

Vol 6 (4) ◽

pp. 407-425 ◽

Cited By ~ 20

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.

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

European Heart Journal ◽

10.1093/eurheartj/ehz746.0030 ◽

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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Combination of µCT and light microscopy for generation-specific stereological analysis of pulmonary arterial branches: a proof-of-concept study

Histochemistry and Cell Biology ◽

10.1007/s00418-020-01946-x ◽

2020 ◽

Cited By ~ 1

Author(s):

Roman Grothausmann ◽

Jonas Labode ◽

Pablo Hernandez-Cerdan ◽

David Haberthür ◽

Ruslan Hlushchuk ◽

...

Keyword(s):

Blood Vessels ◽

Volume Fraction ◽

Pulmonary Vasculature ◽

Chronic Obstructive ◽

Micro Computed Tomography ◽

Vascular Perfusion ◽

Arterial Tree ◽

Color Code ◽

Rabbit Lung ◽

Stereological Analysis

AbstractVarious lung diseases, including pulmonary hypertension, chronic obstructive pulmonary disease or bronchopulmonary dysplasia, are associated with structural and architectural alterations of the pulmonary vasculature. The light microscopic (LM) analysis of the blood vessels is limited by the fact that it is impossible to identify which generation of the arterial tree an arterial profile within a LM microscopic section belongs to. Therefore, we established a workflow that allows for the generation-specific quantitative (stereological) analysis of pulmonary blood vessels. A whole left rabbit lung was fixed by vascular perfusion, embedded in glycol methacrylate and imaged by micro-computed tomography (µCT). The lung was then exhaustively sectioned and 20 consecutive sections were collected every 100 µm to obtain a systematic uniform random sample of the whole lung. The digital processing involved segmentation of the arterial tree, generation analysis, registration of LM sections with the µCT data as well as registration of the segmentation and the LM images. The present study demonstrates that it is feasible to identify arterial profiles according to their generation based on a generation-specific color code. Stereological analysis for the first three arterial generations of the monopodial branching of the vasculature included volume fraction, total volume, lumen-to-wall ratio and wall thickness for each arterial generation. In conclusion, the correlative image analysis of µCT and LM-based datasets is an innovative method to assess the pulmonary vasculature quantitatively.

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Localization and Distribution of Endothelin Receptor Subtypes in Pulmonary Vasculature of Normal and Hypoxia-Exposed Rats

American Journal of Respiratory Cell and Molecular Biology ◽

10.1165/ajrcmb.20.4.3356 ◽

1999 ◽

Vol 20 (4) ◽

pp. 620-630 ◽

Cited By ~ 66

Author(s):

Sanae Soma ◽

Hideki Takahashi ◽

Masashi Muramatsu ◽

Masahiko Oka ◽

Yoshinosuke Fukuchi

Keyword(s):

Pulmonary Vasculature ◽

Receptor Subtypes ◽

Endothelin Receptor

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Transient severe isolated right ventricular hypertrophy in neonates

Cardiology in the Young ◽

10.1017/s1047951103000799 ◽

2003 ◽

Vol 13 (4) ◽

pp. 384-386 ◽

Cited By ~ 2

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.

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