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BMC Pulmonary Medicine Dec 2021Mechanisms of positive effects of pulmonary artery (PA) denervation (PADN) remain poorly understood. The study aimed to evaluate pulmonary hemodynamic changes after PADN... (Comparative Study)
Comparative Study
BACKGROUND
Mechanisms of positive effects of pulmonary artery (PA) denervation (PADN) remain poorly understood. The study aimed to evaluate pulmonary hemodynamic changes after PADN and their association with the extent of PA wall damage in an acute thromboxane A2 (TXA2)-induced pulmonary hypertension (PH) model in swine.
METHODS
In this experimental sham-controlled study, 17 normotensive male white Landrace pigs (the mean weight 36.2 ± 4.5 kg) were included and randomly assigned to group I (n = 9)-PH modeling before and after PADN, group II (n = 4)-PADN only, or group III (n = 4)-PH modeling before and after a sham procedure. Radiofrequency (RF) PADN was performed in the PA trunk and at the proximal parts of the right and left PAs. PA wall lesions were characterized at the autopsy study using histological and the immunohistochemical examination.
RESULTS
In groups I and II, no statistically significant changes in the mean pulmonary arterial pressure nor systemic blood pressure were found after PADN (-0.8 ± 3.4 vs 4.3 ± 8.6 mmHg, P = 0.47; and 6.0 ± 15.9 vs -8.3 ± 7.5 mmHg, P = 0.1; correspondingly). There was a trend towards a lower diastolic pulmonary arterial pressure after PADN in group I when compared with group III during repeat PH induction (34.4 ± 2.9 vs 38.0 ± 0.8; P = 0.06). Despite the presence of severe PA wall damage at the RF application sites, S100 expression was preserved in the majority of PA specimens. The presence of high-grade PA lesions was associated with HR acceleration after PADN (ρ = 0.68, p = 0.03). No significant correlation was found between the grade of PA lesion severity and PA pressure after PADN with or without PH induction.
CONCLUSIONS
Extended PADN does not affect PH induction using TXA2. Significant PA adventitia damage is associated with HR acceleration after PADN. Possible delayed effects of PADN on perivascular nerves and pulmonary hemodynamics require further research in chronic experiments.
Topics: Animals; Blood Pressure; Catheter Ablation; Denervation; Disease Models, Animal; Hemodynamics; Hypertension, Pulmonary; Male; Pulmonary Artery; Swine
PubMed: 34922518
DOI: 10.1186/s12890-021-01786-y -
BMC Cardiovascular Disorders Dec 2021Growth differentiation factor (GDF)-15 is linked to inflammation, cancer, and atherosclerosis. GDF-15 is expressed in most tissues but is extremely induced under...
Characterization of atherosclerotic plaques in blood vessels with low oxygenated blood and blood pressure (Pulmonary trunk): role of growth differentiation factor-15 (GDF-15).
BACKGROUND
Growth differentiation factor (GDF)-15 is linked to inflammation, cancer, and atherosclerosis. GDF-15 is expressed in most tissues but is extremely induced under pathological conditions. Elevated serum levels are suggested as a risk factor and a marker for cardiovascular diseases. However, the cellular sources and the effects of GDF-15 on the cardiovascular system have not been completely elucidated including progression, and morphology of atherosclerotic plaques. Thus, this work aimed to characterize the influence of GDF-15 deficiency on the morphology of atherosclerotic plaques in blood vessels with low-oxygen blood and low blood pressure as the pulmonary trunk (PT), in hypercholesterolemic ApoE mice.
METHODS
GDF-15 ApoE mice were generated by crossbreeding of ApoE- and GDF-15 mice. After feeding a cholesterol-enriched diet (CED) for 20 weeks, samples of the brachiocephalic trunk (BT) and PT were dissected and lumen stenosis (LS) was measured. Furthermore, changes in the cellularity of the PT, amounts of apoptosis-, autophagy-, inflammation- and proliferation-relevant proteins were immunohisto-morphometrically analyzed. Additionally, we examined an atherosclerotic plaque in a human post mortem sample of the pulmonary artery.
RESULTS
After CED the body weight of GDF-15ApoE was 22.9% higher than ApoE. Double knockout mice showed also an 35.3% increase of plasma triglyceride levels, whereas plasma cholesterol was similar in both genotypes. LS in the BT and PT of GDF-15ApoE mice was significantly reduced by 19.0% and by 6.7% compared to ApoE. Comparing LS in PT and BT of the same genotype revealed a significant 38.8% (ApoE) or 26.4% (GDF-15ApoE) lower LS in the PT. Immunohistomorphometry of atherosclerotic lesions in PT of GDF-15ApoE revealed significantly increased levels (39.8% and 7.3%) of CD68 macrophages (MΦ) and α-actin smooth muscle cells than in ApoE. The density of TUNEL , apoptotic cells was significantly (32.9%) higher in plaques of PT of GDF-15ApoE than in ApoE. Analysis of atherosclerotic lesion of a human pulmonary artery showed sm-α-actin, CD68, TUNEL, Ki67, and APG5L/ATG cells as observed in PT. COX-2 and IL-6 immunoreactivities were predominantly located in endothelial cells and subendothelial space. In BT and PT of GDF15ApoE mice the necrotic area was 10% and 6.5% lower than in ApoE. In BT and PT of GDF15ApoE we found 40% and 57% less unstable plaques than ApoE mice.
CONCLUSIONS
Atherosclerotic lesions occur in both, BT and PT, however, the size is smaller in PT, possibly due to the effect of the low-oxygen blood and/or lower blood pressure. GDF-15 is involved in atherosclerotic processes in BT and PT, although different mechanisms (e.g. apoptosis) in these two vessels seem to exist.
Topics: Animals; Apoptosis; Arterial Pressure; Atherosclerosis; Autophagy; Biomarkers; Cell Proliferation; Disease Models, Animal; Growth Differentiation Factor 15; Humans; Hypercholesterolemia; Lipids; Male; Mice, Inbred C57BL; Mice, Knockout, ApoE; Necrosis; Oxygen; Plaque, Atherosclerotic; Pulmonary Artery; Mice
PubMed: 34920697
DOI: 10.1186/s12872-021-02420-9 -
Tidsskrift For Den Norske Laegeforening... Sep 2018
Topics: Adult; Arteriovenous Malformations; Humans; Imaging, Three-Dimensional; Male; Pulmonary Artery; Tomography, X-Ray Computed
PubMed: 30180481
DOI: 10.4045/tidsskr.18.0106 -
Journal of the American College of... Jun 2004Endothelin receptor antagonism has emerged as an important therapeutic strategy in pulmonary arterial hypertension (PAH). Laboratory and clinical investigations have... (Review)
Review
Endothelin receptor antagonism has emerged as an important therapeutic strategy in pulmonary arterial hypertension (PAH). Laboratory and clinical investigations have clearly shown that endothelin (ET)-1 is overexpressed in several forms of pulmonary vascular disease and likely plays a significant pathogenetic role in the development and progression of pulmonary vasculopathy. Oral endothelin receptor antagonists (ERAs) have been shown to improve pulmonary hemodynamics, exercise capacity, functional status, and clinical outcome in several randomized placebo-controlled trials. Bosentan, a dual-receptor antagonist, is approved by the U.S. Food and Drug Administration for class III and IV patients with PAH, based on two phase III trials. In addition to its efficacy as sole therapy, bosentan may have a role as part of a combination of drugs such as a prostanoid or sildenafil. The selective endothelin receptor-A antagonists sitaxsentan and ambrisentan are currently undergoing investigation.
Topics: Endothelin Receptor Antagonists; Endothelin-1; Forecasting; Humans; Hypertension, Pulmonary; Pulmonary Artery; Randomized Controlled Trials as Topic
PubMed: 15194180
DOI: 10.1016/j.jacc.2004.02.042 -
Poultry Science May 2007The pulmonary arterioles react to hypoxia by contraction and to increased pressure and volume by hypertrophy of the muscular wall, referred to as pulmonary vascular... (Review)
Review
The pulmonary arterioles react to hypoxia by contraction and to increased pressure and volume by hypertrophy of the muscular wall, referred to as pulmonary vascular remodeling, both of which increase vascular resistance and result in increased pulmonary arterial pressure. Heart muscle reacts to increased pressure by hypertrophy of cardiac myocytes and thickening of the muscular wall. The heart responds to increased volume by dilation of the chamber that may result in physiologic or pathologic hypertrophy of the muscle wall. Heart muscle cells are very sensitive to hypoxia or other insults, and this may result in death of individual cardiac myocytes with lengthening and thinning of the remaining heart muscle cells and dilation of the chamber in a process called dilated cardiomyopathy.
Topics: Animals; Hypertrophy; Hypoxia; Myocardium; Pressure; Pulmonary Artery
PubMed: 17435039
DOI: 10.1093/ps/86.5.1006 -
Annals of the Academy of Medicine,... Mar 2021
Topics: Angioplasty, Balloon; Chronic Disease; Endarterectomy; Humans; Hypertension, Pulmonary; Pulmonary Artery; Pulmonary Embolism; Singapore
PubMed: 33855327
DOI: 10.47102/annals-acadmedsg.2020126 -
Journal of the American College of... Aug 2020
Topics: Denervation; Endarterectomy; Humans; Hypertension, Pulmonary; Pulmonary Artery; Pulmonary Embolism
PubMed: 32819466
DOI: 10.1016/j.jacc.2020.06.067 -
Antioxidants & Redox Signaling Nov 2019Pulmonary arterial hypertension (PAH) is a progressive disease of the lung vasculature characterized by the proliferation of all vascular wall cell types, including... (Review)
Review
Pulmonary arterial hypertension (PAH) is a progressive disease of the lung vasculature characterized by the proliferation of all vascular wall cell types, including endothelial, smooth muscle, and fibroblasts. The disease rapidly advances into a form with extensive pulmonary vascular remodeling, leading to a rapid increase in pulmonary vascular resistance, which results in right heart failure. Most current research in the PAH field has been focused on the late stage of the disease, largely due to an urgent need for patient treatment options in clinics. Further, the pathobiology of PAH is multifaceted in the advanced disease, and there has been promising recent progress in identifying various pathological pathways related to the late clinical picture. Early stage PAH still requires additional attention from the scientific community, and although the survival of patients with early diagnosis is comparatively higher, the disease develops in patients asymptomatically, making it difficult to identify and treat early. There are several reasons to focus on the early stage of PAH. First, the complexity of late stage disease, owing to multiple pathways being activated in a complex system with intra- and intercellular signaling, leads to an unclear picture of the key contributors to the pathobiology. Second, an understanding of early pathophysiological events can increase the ability to identify PAH patients earlier than what is currently possible. Third, the prompt diagnosis of PAH would allow for the therapy to start earlier, which has proved to be a more successful strategy, and it ensures better survival in PAH patients.
Topics: Animals; Hemolysis; Humans; Inflammation; Oxidative Stress; Pulmonary Arterial Hypertension; Pulmonary Artery; Signal Transduction
PubMed: 31169021
DOI: 10.1089/ars.2018.7673 -
Journal of Medical Case Reports Apr 2021Unilateral pulmonary artery discontinuity is a rare malformation that is associated with other intracardiac abnormalities. Cases accompanied by other cardiac...
BACKGROUND
Unilateral pulmonary artery discontinuity is a rare malformation that is associated with other intracardiac abnormalities. Cases accompanied by other cardiac abnormalities are often missed on prenatal echocardiography. The prenatal diagnosis of isolated unilateral pulmonary artery discontinuity can also be delayed. However, undiagnosed this malformation would have an effect on further prognosis. We report our case of a prenatal diagnosis of pulmonary atresia with ventricular septal defect and left pulmonary artery discontinuity.
CASE PRESENTATION
A 33-year-old Asian woman visited our institution at 24 weeks of gestation because of suspected fetal congenital heart disease. Fetal echocardiography revealed a small atretic main pulmonary artery giving rise to the right pulmonary artery without bifurcation and the left pulmonary artery arising from the ductus arteriosus originating from the left subclavian artery. The neonate was delivered by cesarean section at 37 weeks of gestation. Postnatal echocardiography and multidetector computed tomography showed a right aortic arch, with the small right pulmonary artery originating from the atretic main pulmonary artery and the left pulmonary artery originating from the left subclavian artery. Patency of the ductus arteriosus from the left subclavian artery was maintained with prostaglandin E1. Right ventricular outflow tract reconstruction and pulmonary angioplasty with Gore-Tex graft patch was performed 25th day after birth. Unfortunately, the neonate died because of right heart failure 8 days postoperation.
CONCLUSION
There is a possibility that both pulmonary arteries do not arise from the same great artery (main pulmonary artery or common arterial trunk). Therefore, clinicians should check the origin of both pulmonary arteries.
Topics: Adult; Cesarean Section; Female; Heart Defects, Congenital; Heart Septal Defects, Ventricular; Humans; Infant, Newborn; Pregnancy; Pulmonary Artery; Pulmonary Atresia
PubMed: 33812372
DOI: 10.1186/s13256-021-02750-4 -
Clinical Cardiology Oct 1997The five-part review focuses on selected nonneoplastic diseases of the aorta and pulmonary trunk. Because many more disease affect the aorta compared with the pulmonary... (Review)
Review
The five-part review focuses on selected nonneoplastic diseases of the aorta and pulmonary trunk. Because many more disease affect the aorta compared with the pulmonary trunk and right and left main pulmonary arteries, most of this review will be devoted to disorders of the aorta. Part III of this five-part series discusses the etiology of aortic aneurysms and aortitis.
Topics: Aortic Diseases; Arteritis; Humans; Pulmonary Artery
PubMed: 9377826
DOI: 10.1002/clc.4960201017