Narrowing Of Pulmonary Arteries Research Articles

Percutaneous pulmonary valve implantation in a patient with a single pulmonary artery and distal narrowing.

Percutaneous pulmonary valve implantation is established as a safe and effective method of treating patients with disfunction of right ventricular outflow tract. Modifications of this method allow for an increasingly wider use of this less invasive treatment. We present a staged percutaneous pulmonary valve implantation into a single-branch pulmonary artery in a paediatric patient with tetralogy of Fallot after patch repair.

TAKAYASU'S ARTERITIS: ANAESTHETIC IMPLICATIONS AND MANAGEMENT OF A PATIENT FOR CESAREAN SECTION IN A TERTIARY CARE HOSPITAL

Takayasu's arteritis (TA) is a rare, chronic, inammatory, progressive, idiopathic arteriopathy, aficting young women of reproductive age group, causing narrowing, occlusion, and aneurysms of systemic and pulmonary arteries, especially the aorta and its branches. During pregnancy, such patients warrant special attention. We report here with anesthetic management of a primigravida of 37 week gestation, who suffered from TA scheduled for elective cesarean section by general anaesthesia. The intraoperative period was uneventful. The patient was stable in the postoperative period and was shifted to ward after being monitored in the intensive care unit for 24 h.

Compression of the Pulmonary Artery and Coronary Artery Caused by Pulmonary Epithelioid Hemangioendothelioma: A Case Report.

A 63-year-old woman with a five-month history of pulmonary epithelioid hemangioendothelioma (PEH) presented to the emergency department, due to worsening dyspnea and chest pain. The electrocardiography showed a pattern of ST-segment elevation in leads I, AVL, and poor R-wave progression consistent with anterolateral ischemia. Emergent coronary angiography revealed severe stenosis of the left main coronary artery. Then, contrast-enhanced computed tomography scan indicated the right pulmonary artery and left main coronary artery narrowing by compression of metastasized PEH. Finally, the patient died of deteriorated multi-organ failure.

Techniques for pulmonary artery narrowing in patients with congenital heart disease and ductal-dependent systemic circulation

<h3>ЦЕЛЬ ИССЛЕДОВАНИЯ</h3> Определение интраоперационных критериев эффективности суживания ветвей легочной артерии (ЛА) при коррекции критических врожденных пороков сердца (ВПС). <h3>МАТЕРИАЛ И МЕТОДЫ</h3> Исследованы результаты лечения 37 пациентов с критическими ВПС, которым выполнена гибридная операция: билатеральное суживание ветвей ЛА и стентирование открытого артериального протока (ОАП). Пациенты разделены на три группы с учетом метода операции. Операция по методу №1 проводится в один этап со стентированием ОАП. После срединной стернотомии накладываются две манжеты из сосудистого протеза Gore-Tex шириной 1—2 мм и диаметром 3—3,5 мм. Метод №2 основывается на применении лавсановой нити при суживании ветвей ЛА. Эффективность операций оценивали по изменению инвазивного артериального давления и насыщения крови кислородом после сужения ветвей ЛА. Метод №3 отличается интраоперационной оценкой кровотока в месте сужения ветвей ЛА. Манжету для билатерального суживания ЛА изготавливали из сосудистого протеза Gore-Tex. Операцию по методике №1 выполнили у 14 (37,8%) пациентов, по методике №2 — у 8 (21,6%), по методике №3 — у 15 (40,6%). Для выявления факторов, влияющих на гемодинамическую эффективность суживания ветвей ЛА, определения степени их влияния на результат применен метод множественной логистической регрессии. <h3>РЕЗУЛЬТАТЫ</h3> В результате применения методики №1 соотношение Qp/Qs=1/1 отмечено у 5 (35,7%) пациентов, методики №2 — у 3 (37,5%), методики №3 — у 14 (93,3%). По данным статистического анализа выявлено, что методика №3 (отношение шансов (ОШ) 0,013; 95% ДИ 0,001—0,314; <i>p</i>=0,007) в сочетании с интраоперационной оценкой показателей кровотока в месте суживания левой ветви ЛА (ОШ 17,526; 95% ДИ 1,944—325,462; <i>p</i>=0,045) являются значимыми критериями достижения Qp/Qs=1/1 при суживании ветвей ЛА у детей с критическими ВПС. <h3>ВЫВОД</h3> Билатеральное суживание ветвей ЛА по методике №3 позволяет наиболее эффективно сбалансировать объемную нагрузку малого и большого кругов кровообращения у пациентов с критическими ВПС. Методика №3 в сочетании с интраоперационной оценкой кровотока в месте суживания ветвей ЛА является наиболее оптимальным критерием достижения соотношения Qp/Qs=1/1.

Treatment of pulmonary artery pseudoaneurysms and stenosis with balloon-expandable stents.

We describe our use of balloon-expandable stents in pulmonary arteries for a variety of indications. This is an endovascular technique that provides an alternative treatment option to treat some forms of complex pulmonary artery disease when standard surgical or other endovascular options are not possible. This case series describes the successful treatment of four patients with different pulmonary artery diseases. Indications for stent placement include multiple broad-necked pulmonary artery pseudoaneurysms, symptomatic malignant pulmonary artery narrowing and post-surgical iatrogenic pulmonary artery stenosis. No stent-related complication had been identified from 3 months to 4 years of follow-up. All surviving patients have experienced sustained symptomatic improvement.

Diagnostic Evaluation of Chronic Thromboembolic Pulmonary Hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a distinct form of pulmonary hypertension, uniquely characterized by pulmonary artery narrowing and occlusion from clot material. With advances in medical education and therapeutic options, awareness of CTEPH has grown significantly in recent years. The diagnostic evaluation remains complex, warranting an integrated assessment of history, physical exam, echocardiogram, chest imaging including computerized tomography with angiography, ventilation–perfusion scanning, right heart catheterization, catheter-based pulmonary angiography, and assessment for medical and mechanical CTEPH risk factors. The diagnostic evaluation of CTEPH is reviewed here.

Staged left ventricular recruitment facilitated by Sano conduit upsizing

Staged left ventricular recruitment facilitated by Sano conduit upsizing

Ascending aortic extension to increase aortopulmonary space after comprehensive stage II palliation.

Aortic reconstruction at the time of the comprehensive stage II (CSII) procedure can be complicated by compression within the aortopulmonary space resulting in airway or pulmonary artery narrowing. We describe our experience with 2 patients with hypoplastic left heart syndrome and pulmonary artery stenosis after the CSII procedure. Both patients underwent an aortic extension with a Hemashield interposition graft to open up the aortopulmonary space. The patients were discharged from the hospital. In all cases the aortopulmonary space was enlarged, and the pulmonary arteries and airway were free from compression. Aortic extension is an option to be considered in children with pulmonary artery compression who previously had a CSII procedure.

Galectin-3 Promotes ROS, Inflammation, and Vascular Fibrosis in Pulmonary Arterial Hypertension.

Pulmonary Arterial Hypertension (PAH) is a progressive vascular disease arising from the narrowing of pulmonary arteries (PA) resulting in high pulmonary arterial blood pressure and ultimately right ventricular (RV) failure. A defining characteristic of PAH is the excessive remodeling of PA that includes increased proliferation, inflammation, and fibrosis. There is no cure for PAH nor interventions that effectively impede or reverse PA remodeling, and research over the past several decades has sought to identify novel molecular mechanisms of therapeutic benefit. Galectin-3 (Gal-3; Mac-2) is a carbohydrate-binding lectin that is remarkable for its chimeric structure, comprised of an N-terminal oligomerization domain and a C-terminal carbohydrate-recognition domain. Gal-3 is a regulator of changes in cell behavior that contribute to aberrant PA remodeling including cell proliferation, inflammation, and fibrosis, but its role in PAH is poorly understood. Herein, we summarize the recent literature on the role of Gal-3 in the development of PAH and provide experimental evidence supporting the ability of Gal-3 to influence reactive oxygen species (ROS) production, NOX enzyme expression, inflammation, and fibrosis, which contributes to PA remodeling. Finally, we address the clinical significance of Gal-3 as a target in the development of therapeutic agents as a treatment for PAH.

PIM1 (Moloney Murine Leukemia Provirus Integration Site) Inhibition Decreases the Nonhomologous End-Joining DNA Damage Repair Signaling Pathway in Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) is a fatal disease characterized by the narrowing of pulmonary arteries (PAs). It is now established that this phenotype is associated with enhanced PA smooth muscle cells (PASMCs) proliferation and suppressed apoptosis. This phenotype is sustained in part by the activation of several DNA repair pathways allowing PASMCs to survive despite the unfavorable environmental conditions. PIM1 (Moloney murine leukemia provirus integration site) is an oncoprotein upregulated in PAH and involved in many prosurvival pathways, including DNA repair. The objective of this study was to demonstrate the implication of PIM1 in the DNA damage response and the beneficial effect of its inhibition by pharmacological inhibitors in human PAH-PASMCs and in rat PAH models. Approach and Results: We found in vitro that PIM1 inhibition by either SGI-1776, TP-3654, siRNA (silencer RNA) decreased the phosphorylation of its newly identified direct target KU70 (lupus Ku autoantigen protein p70) resulting in the inhibition of double-strand break repair (Comet Assay) by the nonhomologous end-joining as well as reduction of PAH-PASMCs proliferation (Ki67-positive cells) and resistance to apoptosis (Annexin V positive cells) of PAH-PASMCs. In vivo, SGI-1776 and TP-3654 given 3× a week, improved significantly pulmonary hemodynamics (right heart catheterization) and vascular remodeling (Elastica van Gieson) in monocrotaline and Fawn-Hooded rat models of PAH. We demonstrated that PIM1 phosphorylates KU70 and initiates DNA repair signaling in PAH-PASMCs and that PIM1 inhibitors represent a therapeutic option for patients with PAH.

Galectin-3: A Harbinger of Reactive Oxygen Species, Fibrosis, and Inflammation in Pulmonary Arterial Hypertension.

Significance: Pulmonary arterial hypertension (PAH) is a progressive disease arising from the narrowing of pulmonary arteries (PAs) resulting in high pulmonary arterial blood pressure and ultimately right ventricle (RV) failure. A defining characteristic of PAH is the excessive and unrelenting inward remodeling of PAs that includes increased proliferation, inflammation, and fibrosis. Critical Issues: There is no cure for PAH nor interventions that effectively arrest or reverse PA remodeling, and intensive research over the past several decades has sought to identify novel molecular mechanisms of therapeutic value. Recent Advances: Galectin-3 (Gal-3) is a carbohydrate-binding lectin remarkable for its chimeric structure, composed of an N-terminal oligomerization domain and a C-terminal carbohydrate-recognition domain. Gal-3 has been identified as a regulator of numerous changes in cell behavior that contributes to aberrant PA remodeling, including cell proliferation, inflammation, and fibrosis, but its role in PAH has remained poorly understood until recently. In contrast, pathological roles for Gal-3 have been proposed in cancer and inflammatory and fibroproliferative disorders, such as pulmonary vascular and cardiac fibrosis. Herein, we summarize the recent literature on the role of Gal-3 in the development of PAH. We provide experimental evidence supporting the ability of Gal-3 to influence reactive oxygen species production, NADPH oxidase enzyme expression, and redox signaling, which have been shown to contribute to both vascular remodeling and increased pulmonary arterial pressure. Future Directions: While several preclinical studies suggest that Gal-3 promotes hypertensive pulmonary vascular remodeling, the clinical significance of Gal-3 in human PAH remains to be established. Antioxid. Redox Signal. 00, 000-000.

Multi-detector computed tomography angiographic evaluation of right ventricular outflow tract obstruction and other associated cardiovascular anomalies in tetralogy of Fallot patients.

PurposeTo evaluate various types of right ventricular outflow tract obstruction associated with tetralogy of Fallot (TOF) with emphasis on the abnormality of pulmonary arterial system and other associated cardiovascular anomalies using computed tomography (CT) angiography.Material and methodsWe retrospectively evaluated 184 consecutive previously diagnosed TOF patients who underwent CT angiography in our department.ResultsInfundibular with pulmonary valvular stenosis was the most common type of stenosis (47.28%) found, followed by isolated infundibular stenosis (34.23%). Isolated abnormality of both right and left pulmonary arteries was also noted. Right side aortic arch (23.91%) was the most common associated abnormality followed by double superior vena cava (9.78%).ConclusionsTOF is associated with various types of right ventricular outflow tract obstruction ranging from infundibular narrowing to isolated narrowing of right or left pulmonary arteries and is also associated with various other congenital abnormalities of the cardiovascular system. CT angiography is an excellent imaging modality, which provides comprehensive analysis of various abnormalities associated with TOF.

FHIT, a Novel Modifier Gene in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is characterized by progressive narrowing of pulmonary arteries, resulting in right heart failure and death. BMPR2 (bone morphogenetic protein receptor type 2) mutations account for most familial PAH forms whereas reduced BMPR2 is present in many idiopathic PAH forms, suggesting dysfunctional BMPR2 signaling to be a key feature of PAH. Modulating BMPR2 signaling is therapeutically promising, yet how BMPR2 is downregulated in PAH is unclear. We intended to identify and pharmaceutically target BMPR2 modifier genes to improve PAH. We combined siRNA high-throughput screening of >20,000 genes with a multicohort analysis of publicly available PAH RNA expression data to identify clinically relevant BMPR2 modifiers. After confirming gene dysregulation in tissue from patients with PAH, we determined the functional roles of BMPR2 modifiers in vitro and tested the repurposed drug enzastaurin for its propensity to improve experimental pulmonary hypertension (PH). We discovered FHIT (fragile histidine triad) as a novel BMPR2 modifier. BMPR2 and FHIT expression were reduced in patients with PAH. FHIT reductions were associated with endothelial and smooth muscle cell dysfunction, rescued by enzastaurin through a dual mechanism: upregulation of FHIT as well as miR17-5 repression. Fhit-/- mice had exaggerated hypoxic PH and failed to recover in normoxia. Enzastaurin reversed PH in the Sugen5416/hypoxia/normoxia rat model, by improving right ventricular systolic pressure, right ventricular hypertrophy, cardiac fibrosis, and vascular remodeling. This study highlights the importance of the novel BMPR2 modifier FHIT in PH and the clinical value of the repurposed drug enzastaurin as a potential novel therapeutic strategy to improve PAH.

Identification of Novel Therapeutic Targets for Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are fatal diseases; however, their pathogenesis still remains to be elucidated. We have recently screened novel pathogenic molecules and have performed drug discovery targeting those molecules. Pulmonary artery smooth muscle cells (PASMCs) in patients with PAH (PAH-PASMCs) have high proliferative properties like cancer cells, which leads to thickening and narrowing of distal pulmonary arteries. Thus, we conducted a comprehensive analysis of PAH-PASMCs and lung tissues to search for novel pathogenic proteins. We validated the pathogenic role of the selected proteins by using tissue-specific knockout mice. To confirm its clinical significance, we used patient-derived blood samples to evaluate the potential as a biomarker for diagnosis and prognosis. Finally, we conducted a high throughput screening and found inhibitors for the pathogenic proteins.

156 Inducers of pulmonary arterial hypertension upregulate the expression of plasma membrane calcium atpase 1 in pulmonary artery smooth muscle cells

Pulmonary arterial hypertension (PAH) is a chronic and life-threatening disease with high morbidity and mortality in adult and paediatric patients. PAH is characterised by a progressive narrowing and occlusion of small pulmonary arteries leading to increased pulmonary resistance, right ventricular hypertrophy, and, finally, right ventricular failure. A large body of data has shown that proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) represent key events in the vascular remodelling of pulmonary arteries that occurs during PAH. Levels of cytoplasmic calcium are an important determinant of PASMC proliferation and migration, and failure in maintaining appropriate levels of intracellular calcium are associated with PAH. The plasma membrane calcium ATPase (PMCA) proteins extrude calcium from the cytosol to the extracellular medium, and in doing so, play a critical role in the modulation of intracellular calcium levels. In this work, we have investigated whether inducers of PAH trigger any changes in the expression of PMCA proteins in PASMCs. Analysis of RNA expression levels for PMCA genes has revealed that treatment of PASMCs with PDGF results in a significant increase in the level of the RNA encoding for the protein PMCA1. Interestingly, PMCA1 RNA levels were also elevated in lungs of rats with monocrotaline-induced PAH. No changes were observed in the RNA levels for PMCA4, the other major PMCA isoform expressed in PASMCs. Although previous studies on the regulation of PMCA1 gene expression have identified functional binding sites for the transcription factors NFAT in the PMCA1 promoter region, we show here that PDGF-mediated upregulation of PMCA1 transcriptional expression is independent of activation of the calcineurin/NFAT signalling pathway. Our results suggest the involvement of PMCA1 in PASMC deregulation during PAH, although determination of the link between increased expression of PMCA1 and PAH requires further investigation.

Adventitial Fibroblast Nox4 Expression and ROS Signaling in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease arising from remodeling and narrowing of pulmonary arteries (PA) resulting in high pulmonary arterial blood pressure and ultimately right ventricular failure. Elevated production of reactive oxygen species (ROS) by NADPH oxidase 4 (Nox4), a constitutively active enzyme, has been associated with oxygen sensing, vasomotor control, cellular proliferation, differentiation, migration, apoptosis, senescence, fibrosis, and angiogenesis. Further, elevated expression of Nox4 has been reported in a number of cardiovascular diseases, including atherosclerosis, hypertension, cardiac failure, ischemic stroke, and PAH. However, the cellular location of Nox4 and its contribution to aberrant vascular remodeling in PAH remains poorly understood. The goal of this review is to summarize the recent literature on the enzymatic regulation of Nox4 in the production of ROS in PAH. In the vascular wall, Nox4 is present in fibroblasts, a primary cell of the adventitia, and matches the adventitial location of ROS production in PAH. Further, in adventitial fibroblasts, Nox4 overexpression stimulates migration and proliferation as well as matrix gene expression. Collectively, reports indicate that Nox4 contributes to altered fibroblast behavior, ROS production leading to hypertensive vascular remodeling and the development of PAH. Finally, we address the functional significance of Nox4 in fibroblasts, and also suggest an "outside in" (adventitial) process of vascular remodeling that is mediated by Nox4, which although has physiological roles in the intimal layer (i.e., endothelium), may also have pathologic importance in the adventitial layer of the vascular wall through signaling in fibroblasts.

P46 Dextrocardia and right atrial isomerism associated with congenital trifurcation of trachea

Background A 34 weeks gestation baby was born with complex cardiac congenital heart disease i.e. dextrocardia, right atrial isomerism and moderate pulmonary stenosis. The baby was ventilated because of prematurity and poor respiratory effort. However, later on during the course, the baby failed multiple attempts at extubation. Case Report This is about a white Caucasian female who was born at 34 weeks. She had antenatal diagnosis of right atrial isomerism, dextrocardia and asplenia. Postnatally, she had moderate pulmonary stenosis. Her pulmonary flow was moderately reduced necessitating a BT shunt earlier on. She was ventilated from birth due to prematurity and poor respiratory effort however a few weeks later, an attempt to extubate her failed. Multiple attempts at extubation later on were unsuccessful. This prompted a flexible bronchoscopy which showed trifurcation of trachea. This included a morphological right bronchus and two left bronchus. One of the left bronchus ended in a blind loop. There was moderate tracheomalacia as well. A tracheostomy was eventually performed for respiratory support. In the course of time, pulmonary flow deteriorated again due to supravalvular and valvular stenosis of undetermined aetiology. Hence a right ventricular to pulmonary artery conduit was performed. Discussion Trifurcate trachea is very rare and its association with pulmonary artery stenosis was unrelated in our case but it is important to look for structural and functional association of trifurcate trachea with pulmonary artery narrowing.

NADPH oxidase 4 is expressed in pulmonary artery adventitia and contributes to hypertensive vascular remodeling.

Pulmonary hypertension (PH) is a progressive disease arising from remodeling and narrowing of pulmonary arteries (PAs) resulting in high pulmonary blood pressure and ultimately right ventricular failure. Elevated production of reactive oxygen species by NADPH oxidase 4 (Nox4) is associated with increased pressure in PH. However, the cellular location of Nox4 and its contribution to aberrant vascular remodeling in PH remains poorly understood. Therefore, we sought to identify the vascular cells expressing Nox4 in PAs and determine the functional relevance of Nox4 in PH. Elevated expression of Nox4 was detected in hypertensive PAs from 3 rat PH models and human PH using qualititative real-time reverse transcription polymerase chain reaction, Western blot, and immunofluorescence. In the vascular wall, Nox4 was detected in both endothelium and adventitia, and perivascular staining was prominently increased in hypertensive lung sections, colocalizing with cells expressing fibroblast and monocyte markers and matching the adventitial location of reactive oxygen species production. Small-molecule inhibitors of Nox4 reduced adventitial reactive oxygen species generation and vascular remodeling as well as ameliorating right ventricular hypertrophy and noninvasive indices of PA stiffness in monocrotaline-treated rats as determined by morphometric analysis and high-resolution digital ultrasound. Nox4 inhibitors improved PH in both prevention and reversal protocols and reduced the expression of fibroblast markers in isolated PAs. In fibroblasts, Nox4 overexpression stimulated migration and proliferation and was necessary for matrix gene expression. These findings indicate that Nox4 is prominently expressed in the adventitia and contributes to altered fibroblast behavior, hypertensive vascular remodeling, and development of PH.

G244(P) “Blessing in Disguise”: Noonan Syndrome with JMML

AimsDr Jacqueline Noonan (1962) identified a cohort of patients with typical facial features, short stature, pulmonary artery narrowing and chest deformities. Subsequently they were recognised as having Noonan syndrome (NS);...

Pulmonary regurgitation and pulmonary branch kinking: long-term complication in adults with repaired tetrallogy of Fallot

Cardiologia CROATICA The major long-term complication of tetralogy of Fallot repair is pulmonary valve insufficiency, which leads to right heart failure. Other problems include atrial and ventricular arrhythmias and sudden cardiac death. We report a case of progressive pulmonary valve regurgitation late after tetralogy of Fallot correction. A 26-year old woman with history of Ductus Botalli closure and complete tetralogy of Fallot correction at the age of two, was evaluated for palpitation, intermittent leg edema, progressive exertion intolerance New York Heart Association (NYHA) functional class II/III and a syncope episode. On examination, sinus rhythm and a systolic and early diastolic murmur was noted at the high left sternal border and at the back. Electrocardiography shows right ventricular (RV) hypertrophy with a right bundle branch block. First transthoracic echocardiogram (TTE) showed right ventricle hypertrophy (Figure 1) and mild pulmonary valve regurgitation. The presence of Doppler flow turbulence and increased velocity jet in the left branch pulmonary artery was suggesting the stenosis. Magnetic resonance imaging (MRI) also showed right ventricular hypertrophy, mild pulmonary regurgitation and narrowing of the main pulmonary artery at branching (diameter 12 mm / 20 mm) suggesting mild stenosis. Cardiac catheterization confirmed the diagnosis of anomal coronary artery origin, all from the right coronary sinus. Left pulmonary artery stenosis with pressure gradient less than 20 mmHg was detected on right pulmonary angiography. A computed tomographic scan of thorax was further arranged to delineate the pulmonary artery anatomy; this confirmed mild left branch pulmonary artery narrowing. Perfusion lung scan ratio was 65% right to 35% left. In 6 months follow-up, progressive dyspnea and exercise intolerance occurred. Control TTE revealed significant impairment of pulmonary regurgitation (Figure 2). Stress TTE confirmed increase in pulmonary regurgitation while significant pulmonary transvalvular and peripheral pulmonary gradient remained the same. Patient was scheduled for surgery. At operation, the main left pulmonary artery was found to be kinked with adhesions. The annulus of the pulmonary valve was dilated and one of the cusps was completely destructed. Left pulmonary artery unkinking and pulmonary bioprosthetic valve replacement was done. Soon after operation the patient made an uneventful recovery. At her 6-month follow-up, she remains in NYHA functional class I with no symptoms, follow-up TTE revealed reversal remodeling of the RV, normal bioprosthetic function, transpulmonary and peripheral flow. Proπireni saaeetak / Extended abstract