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JACC. Cardiovascular Imaging Aug 2023
Topics: Humans; Pulmonary Circulation; Predictive Value of Tests; Heart; Hypertension, Pulmonary; Pulmonary Artery; Heart Ventricles; Ventricular Function, Right
PubMed: 37115162
DOI: 10.1016/j.jcmg.2023.03.002 -
American Journal of Respiratory and... Jun 2021Data on the molecular mechanisms that regulate platelet-pulmonary endothelial adhesion under conditions of hypoxia are lacking, but may have important therapeutic...
Data on the molecular mechanisms that regulate platelet-pulmonary endothelial adhesion under conditions of hypoxia are lacking, but may have important therapeutic implications. To identify a hypoxia-sensitive, modifiable mediator of platelet-pulmonary artery endothelial cell adhesion and thrombotic remodeling. Network medicine was used to profile protein-protein interactions in hypoxia-treated human pulmonary artery endothelial cells. Data from liquid chromatography-mass spectrometry and microscale thermophoresis informed the development of a novel antibody (Ab) to inhibit platelet-endothelial adhesion, which was tested in cells from patients with chronic thromboembolic pulmonary hypertension (CTEPH) and three animal models . The protein NEDD9 was identified in the hypoxia thrombosome network . Compared with normoxia, hypoxia (0.2% O) for 24 hours increased HIF-1α (hypoxia-inducible factor-1α)-dependent NEDD9 upregulation . Increased NEDD9 was localized to the plasma-membrane surface of cells from control donors and patients with CTEPH. In endarterectomy specimens, NEDD9 colocalized with the platelet surface adhesion molecule P-selectin. Our custom-made anti-NEDD9 Ab targeted the NEDD9-P-selectin interaction and inhibited the adhesion of activated platelets to pulmonary artery endothelial cells from control donors and from patients with CTEPH . Compared with control mice, platelet-pulmonary endothelial aggregates and pulmonary hypertension induced by ADP were decreased in NEDD9 mice or wild-type mice treated with the anti-NEDD9 Ab, which also decreased chronic pulmonary thromboembolic remodeling . The NEDD9-P-selectin protein-protein interaction is a modifiable target with which to inhibit platelet-pulmonary endothelial adhesion and thromboembolic vascular remodeling, with potential therapeutic implications for patients with disorders of increased hypoxia signaling pathways, including CTEPH.
Topics: Adaptor Proteins, Signal Transducing; Animals; Blood Platelets; Cell Adhesion; Cells, Cultured; Endothelial Cells; Female; Humans; Hypoxia; Male; Mice; Middle Aged; Models, Animal; Pulmonary Circulation; Pulmonary Embolism; Signal Transduction
PubMed: 33523764
DOI: 10.1164/rccm.202003-0719OC -
Indian Heart Journal 2017The diagnosis of idiopathic dilatation of pulmonary artery is challenging because its clinical recognition is difficult and various other causes of dilated pulmonary... (Review)
Review
The diagnosis of idiopathic dilatation of pulmonary artery is challenging because its clinical recognition is difficult and various other causes of dilated pulmonary artery need to be excluded. The clinical findings mimic various common cardiac disorders and both invasive and non-invasive investigations should be done to arrive at the diagnosis. It is a known clinical entity but etiology and pathophysiology are largely unknown. The current echocardiographic and catheterization based diagnostic criteria, may not be satisfied completely in a particular patient and need to be revisited in view of newer imaging modalities. There is paucity of information about the natural history of the disease with attendant lack of clarity in treatment guidelines. Certain cases may progress to huge dilatation and consequent serious implications. It is a rare disease and is the diagnosis of exclusion.
Topics: Dilatation, Pathologic; Humans; Pulmonary Artery; Pulmonary Circulation; Ultrasonography, Doppler; Vascular Diseases
PubMed: 28228295
DOI: 10.1016/j.ihj.2016.07.009 -
Aerospace Medicine and Human Performance Aug 2019Changes in gravity or body position provoke changes in hydrostatic pressure in the arterial system and in venous return. Potential asymmetries between left (Q) and...
Changes in gravity or body position provoke changes in hydrostatic pressure in the arterial system and in venous return. Potential asymmetries between left (Q) and right ventricular (Q) cardiac output during transient gravity changes were investigated. It was hypothesized that blood volume is temporarily stored in the pulmonary vessels, with amount and duration depending on the level and directions of gravity. Eight healthy, male subjects (32 ± 3 yr, 182 ± 7 cm, 82 ± 6 kg) were tested on a tilt seat (TS), in a long arm human centrifuge (laHC), and during parabolic flights (PF). The gravitational changes during PF were reconstructed by changing gravity in a laHC and different body positions on a TS. All participants were tested in the seated, resting position. Heart rate and blood pressure were recorded continuously and Q was calculated, applying the Modelflow Algorithm. Gas exchange was measured breath-by-breath. Q was calculated from these data according to the Fick Principle. Four sequences were superimposed and analyzed by ANOVA with the factors Time, Ventricle (Q, Q), and Mode (TS, PF, laHC). After reductions in gravity Q and Q were transiently desynchronized. ANOVA showed no main effect for Mode, but significant changes were found for Time and Ventricle and all interactions. Phases of reduced gravity seem to lead to transiently increased storage of blood volume inside the pulmonary vascular system. A more detailed understanding of these mechanisms might help to describe the compliance of the pulmonary vascular system in diseases of the pulmonary circulation.
Topics: Adaptation, Physiological; Adult; Blood Pressure; Cardiac Output; Centrifugation; Healthy Volunteers; Heart Rate; Humans; Hypergravity; Male; Posture; Pulmonary Circulation; Space Flight
PubMed: 31331418
DOI: 10.3357/AMHP.5300.2019 -
Heart and Vessels Jul 2022There is a unique hyperbolic relationship between pulmonary vascular resistance (Rp) and compliance (Cp); however, the characteristics of this coupling curve in...
There is a unique hyperbolic relationship between pulmonary vascular resistance (Rp) and compliance (Cp); however, the characteristics of this coupling curve in pulmonary blood flow alterations remains unknown in children with congenital heart disease. We aimed to explore the Rp-Cp coupling and resistant-compliance (RC) time among them. We retrospectively reviewed catheterization data and calculated Rp and Cp in 217 subjects with ventricular septal defect. Median age and weight at catheterization were 2.8 (1.7-4.4) months and 4.3 (3.7-5.3) kg, respectively. Pulmonary hemodynamic parameters were as follows: mean pulmonary arterial pressure: 36 (28-43) mmHg; the amount of pulmonary blood flow (Qp): 14.2 (11.6-17.6) L/min/m; Rp: 1.95 (1.38-2.59) Wood unit m; Cp: 2.98 (2.42-3.88) mmHg/mL/m; and RC time: 0.35 (0.30-0.40) s. RC time remained unchanged according to alterations in Qp (P = 0.206); however, the relationship between logarithm transformations of Rp and Cp showed more steeper according to an increase in Qp. The pulmonary circulation depends upon Cp rather than Rp according to the degree of Qp despite the constancy in RC time. We should take both Rp and Cp into consideration when evaluating the pulmonary circulation among children with congenital heart disease.
Topics: Cardiac Catheterization; Child; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Pulmonary Artery; Pulmonary Circulation; Retrospective Studies; Vascular Resistance
PubMed: 35001144
DOI: 10.1007/s00380-021-02009-4 -
The European Respiratory Journal Jul 2016
Topics: Humans; Pulmonary Circulation
PubMed: 27365505
DOI: 10.1183/13993003.00860-2016 -
Archivos de Bronconeumologia Apr 2022
Topics: COVID-19; Humans; Pulmonary Circulation; Thrombosis
PubMed: 34054194
DOI: 10.1016/j.arbres.2021.05.007 -
Heart Failure Clinics Jul 2018Most healthy subjects can develop a subclinical interstitial pulmonary edema that is a complex and multifactor phenomenon, still with unanswered questions, and might be... (Review)
Review
Most healthy subjects can develop a subclinical interstitial pulmonary edema that is a complex and multifactor phenomenon, still with unanswered questions, and might be one line of defense against the development of severe symptomatic lung edema. Whether the acute, reversible increase in lung fluid content is really an innocent and benign part of the adaptation to extreme physiologic condition or rather the clinically relevant marker of an individual vulnerability to life-threatening high altitude pulmonary edema remains to be established in future studies. Thus the question if encouraging more conservative habits to climb is right or not remains open.
Topics: Adaptation, Physiological; Altitude; Altitude Sickness; Heart Ventricles; Humans; Hypertension, Pulmonary; Hypoxia; Lung; Pulmonary Circulation; Vascular Resistance
PubMed: 29966631
DOI: 10.1016/j.hfc.2018.02.008 -
Clinics in Perinatology Mar 2024Fetal lungs have fewer and smaller arteries with higher pulmonary vascular resistance (PVR) than a newborn. As gestation advances, the pulmonary circulation becomes more... (Review)
Review
Fetal lungs have fewer and smaller arteries with higher pulmonary vascular resistance (PVR) than a newborn. As gestation advances, the pulmonary circulation becomes more sensitive to changes in pulmonary arterial oxygen tension, which prepares them for the dramatic drop in PVR and increase in pulmonary blood flow (PBF) that occur when the baby takes its first few breaths of air, thus driving the transition from fetal to postnatal circulation. Dynamic and intricate regulatory mechanisms control PBF throughout development and are essential in supporting gas exchange after birth. Understanding these concepts is crucial given the role the pulmonary vasculature plays in the development of complications with transition, such as in the setting of persistent pulmonary hypertension of the newborn and congenital heart disease. An improved understanding of pulmonary vascular regulation may reveal opportunities for better clinical management.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Lung; Fetus; Pulmonary Circulation; Prenatal Care; Vascular Resistance
PubMed: 38325936
DOI: 10.1016/j.clp.2023.11.003 -
American Journal of Respiratory and... Aug 2023
Topics: Humans; Hypertension, Pulmonary; Pulmonary Artery; Pulmonary Circulation
PubMed: 37348119
DOI: 10.1164/rccm.202306-0990ED