Stretch-induced contraction in pulmonary arteries.

PubMed

Kulik, T J; Evans, J N; Gamble, W J

1988-12-01

Stretch stimulates contraction of systemic blood vessels, but the response has not been described in pulmonary vessels. To determine whether pulmonary arteries contract when stretched, isolated cylindrical segments of pulmonary arteries were suspended between two parallel wires, stretched, and the active force was generated in response to stretch measured. Eighty-nine percent of segments from small (in situ diameter less than 1,000 microns) feline pulmonary arteries contracted when stretched, and in 65% of these the magnitude of stretch was related to the magnitude of contraction. Large (in situ diameter greater than or equal to 1,000 microns) feline pulmonary arteries did not contract with stretch. Multiple, rapidly repeated stretches resulted in a diminution of active force development. Stretch-induced contraction required external Ca2+ and was abolished by diltiazem (10 microns), but it was not affected by phenoxybenzamine, phentolamine, diethylcarbamazine, or mechanical removal of endothelium. Indomethacin blunted but did not abolish stretch-induced contraction, an effect that may have been nonspecific. This study suggests that stretch can act, probably directly, on smooth muscle in small feline pulmonary arteries to elicit contraction and that it may be a determinant of pulmonary vascular tone. In addition, feline pulmonary arteries are suitable for the in vitro study of stretch-induced contraction.

Pediatric Cardiac Intensive Care Society 2014 Consensus Statement: Pharmacotherapies in Cardiac Critical Care Pulmonary Hypertension.

PubMed

Kim, John S; McSweeney, Julia; Lee, Joanne; Ivy, Dunbar

2016-03-01

To review the pharmacologic treatment options for pulmonary arterial hypertension in the cardiac intensive care setting and summarize the most-recent literature supporting these therapies. Literature search for prospective studies, retrospective analyses, and case reports evaluating the safety and efficacy of pulmonary arterial hypertension therapies. Mechanisms of action and pharmacokinetics, treatment recommendations, safety considerations, and outcomes for specific medical therapies. Specific targeted therapies developed for the treatment of adult patients with pulmonary arterial hypertension have been applied for the benefit of children with pulmonary arterial hypertension. With the exception of inhaled nitric oxide, there are no pulmonary arterial hypertension medications approved for children in the United States by the Food and Drug Administration. Unfortunately, data on treatment strategies in children with pulmonary arterial hypertension are limited by the small number of randomized controlled clinical trials evaluating the safety and efficacy of specific treatments. The treatment options for pulmonary arterial hypertension in children focus on endothelial-based pathways. Calcium channel blockers are recommended for use in a very small, select group of children who are responsive to vasoreactivity testing at cardiac catheterization. Phosphodiesterase type 5 inhibitor therapy is the most-commonly recommended oral treatment option in children with pulmonary arterial hypertension. Prostacyclins provide adjunctive therapy for the treatment of pulmonary arterial hypertension as infusions (IV and subcutaneous) and inhalation agents. Inhaled nitric oxide is the first-line vasodilator therapy in persistent pulmonary hypertension of the newborn and is commonly used in the treatment of pulmonary arterial hypertension in the ICU. Endothelin receptor antagonists have been shown to improve exercise tolerance and survival in adult patients with pulmonary arterial hypertension. Soluble guanylate cyclase stimulators are the first drug class to be Food and Drug Administration approved for the treatment of chronic thromboembolic pulmonary hypertension. Literature and data supporting the safe and effective use of pulmonary arterial hypertension therapies in children in the cardiac intensive care are limited. Extrapolation of adult data has afforded safe medical treatment of pulmonary hypertension in children. Large multicenter trials are needed in the search for safe and effective therapy of pulmonary hypertension in children.

The cancer theory of pulmonary arterial hypertension

PubMed Central

Boucherat, Olivier; Vitry, Geraldine; Trinh, Isabelle; Paulin, Roxane; Provencher, Steeve; Bonnet, Sebastien

2017-01-01

Pulmonary arterial hypertension (PAH) remains a mysterious killer that, like cancer, is characterized by tremendous complexity. PAH development occurs under sustained and persistent environmental stress, such as inflammation, shear stress, pseudo-hypoxia, and more. After inducing an initial death of the endothelial cells, these environmental stresses contribute with time to the development of hyper-proliferative and apoptotic resistant clone of cells including pulmonary artery smooth muscle cells, fibroblasts, and even pulmonary artery endothelial cells allowing vascular remodeling and PAH development. Molecularly, these cells exhibit many features common to cancer cells offering the opportunity to exploit therapeutic strategies used in cancer to treat PAH. In this review, we outline the signaling pathways and mechanisms described in cancer that drive PAH cells’ survival and proliferation and discuss the therapeutic potential of antineoplastic drugs in PAH. PMID:28597757

Hypoxic pulmonary vasoconstriction in isolated mouse pulmonary arterial vessels.

PubMed

Strielkov, Ievgen; Krause, Nicole Catherine; Sommer, Natasha; Schermuly, Ralph Theo; Ghofrani, Hossein Ardeschir; Grimminger, Friedrich; Gudermann, Thomas; Dietrich, Alexander; Weissmann, Norbert

2018-06-19

What is the central question of this study? Hypoxic pulmonary vasoconstriction has never been characterized in isolated mouse pulmonary arteries of different generations in detail. What is the main finding and its importance? We found that only small intrapulmonary arteries (80 - 200 μm in diameter) exhibit hypoxic pulmonary vasoconstriction. The observed response was sustained, significantly potentiated by depolarization-induced preconstriction, and not dependent on endothelium and TRPC6 channels. Hypoxic pulmonary vasoconstriction (HPV) is a physiological response of pulmonary arteries, which adapts lung perfusion to regional ventilation. Properties of hypoxic pulmonary vasoconstriction (HPV) vary significantly between animal species. Despite extensive use of mouse models in studies of HPV, this physiological response has never been characterized in isolated mouse pulmonary arteries in detail. We investigated the effect of 80-min exposure to hypoxia on tone in mouse pulmonary arteries of different generations in the presence and absence of preconstriction using wire myography. Hypoxia induced a sustained relaxation in non-preconstricted extrapulmonary arteries (500 - 700 μm in diameter), but not in the presence of KCl-induced preconstriction. Large intrapulmonary arteries (450 - 650 μm) did not exhibit a significant response to the hypoxic challenge. By contrast, in small intrapulmonary arteries (80 - 200 μm), hypoxia elicited a slowly developing sustained constriction, which was independent of endothelium. The response was significantly potentiated in arteries preconstricted with KCl, but not with U46619. HPV was not altered in pulmonary arteries of TRPC6-deficient mice, which suggests that this response corresponds to the sustained phase of biphasic HPV observed earlier in isolated, buffer-perfused, and ventilated mouse lungs. In conclusion, we have established the protocol allowing to study sustained HPV in isolated mouse pulmonary arteries. The obtained data may be useful for future studies of HPV mechanisms in mice. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Vascular Ehlers-Danlos Syndrome With a Novel Missense COL3A1 Mutation Present With Pulmonary Complications and Iliac Arterial Dissection.

PubMed

Gu, Guangchao; Yang, Hang; Cui, Lijia; Fu, Yuanyuan; Li, Fangda; Zhou, Zhou; Zheng, Yuehong

2018-02-01

Vascular Ehlers-Danlos syndrome (vEDS) is a life-threatening connective tissue disorder due to its high tendency of arterial and organ rupture. Pulmonary complications in vEDS are rare. We present a young male patient with vEDS who developed severe pulmonary complications and severe rupture of the iliac artery at different stages of his life. Vascular Ehlers-Danlos syndrome was diagnosed based on clinical manifestations and confirmed by the identification of COL3A1 gene mutation. Due to high bleeding tendency and weak cardiopulmonary capacity, conservative treatment was taken for him. To our knowledge, this is the first report of vEDS case in which the patient developed both pulmonary complications and dissection of large arteries. Our report emphasizes the importance of considering vEDS when an adolescent develops unexplained pulmonary cysts with fragility of lung tissues. Genetic counseling and close monitoring should be performed for earlier diagnosis and prevention of severe complications of large arteries. The typical presentations of vEDS were also discussed by means of a review of case reports on vEDS with pulmonary complications.

[Pulmonary hypertension associated with congenital heart disease and Eisenmenger syndrome].

PubMed

Calderón-Colmenero, Juan; Sandoval Zárate, Julio; Beltrán Gámez, Miguel

2015-01-01

Pulmonary arterial hypertension is a common complication of congenital heart disease (CHD). Congenital cardiopathies are the most frequent congenital malformations. The prevalence in our country remains unknown, based on birthrate, it is calculated that 12,000 to 16,000 infants in our country have some cardiac malformation. In patients with an uncorrected left-to-right shunt, increased pulmonary pressure leads to vascular remodeling and endothelial dysfunction secondary to an imbalance in vasoactive mediators which promotes vasoconstriction, inflammation, thrombosis, cell proliferation, impaired apotosis and fibrosis. The progressive rise in pulmonary vascular resistance and increased pressures in the right heart provocated reversal of the shunt may arise with the development of Eisenmenger' syndrome the most advanced form de Pulmonary arterial hypertension associated with congenital heart disease. The prevalence of Pulmonary arterial hypertension associated with CHD has fallen in developed countries in recent years that is not yet achieved in developing countries therefore diagnosed late as lack of hospital infrastructure and human resources for the care of patients with CHD. With the development of targeted medical treatments for pulmonary arterial hypertension, the concept of a combined medical and interventional/surgical approach for patients with Pulmonary arterial hypertension associated with CHD is a reality. We need to know the pathophysiological factors involved as well as a careful evaluation to determine the best therapeutic strategy. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Pulmonary hypertension in patients with congenital portosystemic venous shunt: a previously unrecognized association.

PubMed

Ohno, Takuro; Muneuchi, Jun; Ihara, Kenji; Yuge, Tetsuji; Kanaya, Yoshiaki; Yamaki, Shigeo; Hara, Toshiro

2008-04-01

Pulmonary arterial hypertension has been reported to be observed in association with acquired portal hypertension. However, the contribution of congenital anomalies occurring in the portal system to the development of pulmonary arterial hypertension remains to be elucidated. Nine patients with congenital portosystemic venous shunt were studied from January 1990 through September 2005. Patent ductus venosus was detected in 5 patients, including 3 patients with an absence of the portal vein. The presence of either a gastrorenal or splenorenal shunt was evident in another 4 patients. Six patients had a history of hypergalactosemia with normal enzyme activities, as seen during neonatal screening. Six (66.7%) of the 9 patients were identified to have clinically significant pulmonary arterial hypertension (mean pulmonary artery pressure: 34-79 mm Hg; pulmonary vascular resistances: 5.12-38.07 U). The median age at the onset of pulmonary arterial hypertension was 12 years and 3 months. Histologic studies of lung specimens, which were available in 4 of the 9 patients with congenital portosystemic venous shunt, showed small arterial microthrombotic lesions in 3 patients. This characteristic finding was recognized even in the congenital portosystemic venous shunt patients without PAH. This study demonstrated thromboembolic pulmonary arterial hypertension to be a crucial complication in congenital portosystemic venous shunt, and this pathologic state may be latently present in patients with pulmonary arterial hypertension of unknown etiology.

Morphometry-based impedance boundary conditions for patient-specific modeling of blood flow in pulmonary arteries.

PubMed

Spilker, Ryan L; Feinstein, Jeffrey A; Parker, David W; Reddy, V Mohan; Taylor, Charles A

2007-04-01

Patient-specific computational models could aid in planning interventions to relieve pulmonary arterial stenoses common in many forms of congenital heart disease. We describe a new approach to simulate blood flow in subject-specific models of the pulmonary arteries that consists of a numerical model of the proximal pulmonary arteries created from three-dimensional medical imaging data with terminal impedance boundary conditions derived from linear wave propagation theory applied to morphometric models of distal vessels. A tuning method, employing numerical solution methods for nonlinear systems of equations, was developed to modify the distal vasculature to match measured pressure and flow distribution data. One-dimensional blood flow equations were solved with a finite element method in image-based pulmonary arterial models using prescribed inlet flow and morphometry-based impedance at the outlets. Application of these methods in a pilot study of the effect of removal of unilateral pulmonary arterial stenosis induced in a pig showed good agreement with experimental measurements for flow redistribution and main pulmonary arterial pressure. Next, these methods were applied to a patient with repaired tetralogy of Fallot and predicted insignificant hemodynamic improvement with relief of the stenosis. This method of coupling image-based and morphometry-based models could enable increased fidelity in pulmonary hemodynamic simulation.

Right Pulmonary Artery Distensibility Index (RPAD Index). A field study of an echocardiographic method to detect early development of pulmonary hypertension and its severity even in the absence of regurgitant jets for Doppler evaluation in heartworm-infected dogs.

PubMed

Venco, Luigi; Mihaylova, Liliya; Boon, June A

2014-11-15

Despite the term "heartworm disease" Dirofilaria immitis infection in dogs should be considered a pulmonary arterial disease that might only involve the right heart structures in its late stage. Chronic infection by adult heartworms in dogs results in proliferative endoarteritis leading to progressively increasing pulmonary artery pressure due to reduced elasticity. Elasticity allows the pulmonary arteries to stretch in response to each pulse and helps maintain a relatively constant pressure in the arteries despite the pulsating nature of the blood flow. Pulmonary artery distensibility for both acute and chronic pulmonary hypertension has been investigated in humans using MRI and has been correlated with the severity of hypertension and its outcome and treatment response. The aim of the present study was to investigate whether echocardiographic measurement of the percentage change in diameter of the right pulmonary artery in systole and diastole (distensibility) may be of value in assessing the presence and severity of pulmonary hypertension in heartworm-infected dogs. The Right Pulmonary Artery Distensibility Index (RPAD Index) (which is calculated as the difference in diameter of the right pulmonary artery in systole and diastole) was calculated in healthy and naturally infected heartworm-positive dogs. The right pulmonary artery was chosen because it is usually affected earlier and to a greater degree. Data were obtained from healthy heartworm-free dogs without any clinical, radiographic, or echocardiographic signs of pulmonary hypertension; naturally infected heartworm-positive dogs in different stages of the disease in which pulmonary pressure could be measured by Doppler echocardiography (using tricuspid and or pulmonary regurgitation velocity and pressure gradient); and naturally infected heartworm-positive dogs in different stages of the disease (with or without tricuspid and or pulmonary regurgitation) in which the pulmonary pressure was measured invasively and noninvasively if possible. Results of these evaluations indicated that RPAD Index is a valuable method for early detection of the presence and severity of pulmonary hypertension in heartworm-infected dogs even in the absence of regurgitant jets for Doppler evaluation and that there is a strong correlation between the RPAD Index and the level of pulmonary hypertension. Copyright © 2014 Elsevier B.V. All rights reserved.

Does exercise pulmonary hypertension exist?

PubMed

Lau, Edmund M; Chemla, Denis; Whyte, Kenneth; Kovacs, Gabor; Olschewski, Horst; Herve, Philippe

2016-09-01

The exercise definition of pulmonary hypertension using a mean pulmonary artery pressure threshold of greater than 30 mmHg was abandoned following the 4th World Pulmonary Hypertension Symposium in 2008, as this definition was not supported by evidence and healthy individuals frequently exceed this threshold. Meanwhile, the clinical value of exercise pulmonary hemodynamic testing has also been questioned. Recent data support the notion that an abnormal pulmonary hemodynamic response during exercise (or exercise pulmonary hypertension) is associated with symptoms and exercise limitation. Pathophysiologic mechanisms accounting for the development of exercise pulmonary hypertension include increased vascular resistance, excessive elevation in left atrial pressure and/or increased volume of trapped air during exercise, resulting in a steep rise in pulmonary artery pressure relative to cardiac output. Recent evidence suggests that exercise pulmonary hypertension may be defined by a mean pulmonary artery pressure surpassing 30 mmHg together with a simultaneous total pulmonary resistance exceeding 3 WU. Exercise pulmonary hypertension is a clinically relevant entity and an improved definition has been suggested based on new evidence. Exercise pulmonary hemodynamics may help unmask early or latent disease, particularly in populations that are at high risk for the development of pulmonary hypertension.

A Non-Invasive Assessment of Cardiopulmonary Hemodynamics with MRI in Pulmonary Hypertension

PubMed Central

Bane, Octavia; Shah, Sanjiv J.; Cuttica, Michael J.; Collins, Jeremy D.; Selvaraj, Senthil; Chatterjee, Neil R.; Guetter, Christoph; Carr, James C.; Carroll, Timothy J.

2015-01-01

Purpose We propose a method for non-invasive quantification of hemodynamic changes in the pulmonary arteries resulting from pulmonary hypertension (PH). Methods Using a two-element windkessel model, and input parameters derived from standard MRI evaluation of flow, cardiac function and valvular motion, we derive: pulmonary artery compliance (C), mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), pulmonary capillary wedge pressure (PCWP), time-averaged intra-pulmonary pressure waveforms and pulmonary artery pressures (systolic (sPAP) and diastolic (dPAP)). MRI results were compared directly to reference standard values from right heart catheterization (RHC) obtained in a series of patients with suspected pulmonary hypertension (PH). Results In 7 patients with suspected PH undergoing RHC, MRI and echocardiography, there was no statistically significant difference (p<0.05) between parameters measured by MRI and RHC. Using standard clinical cutoffs to define PH (mPAP ≥ 25 mmHg), MRI was able to correctly identify all patients as having pulmonary hypertension, and to correctly distinguish between pulmonary arterial (mPAP≥ 25 mmHg, PCWP<15 mmHg) and venous hypertension (mPAP ≥ 25 mmHg, PCWP ≥ 15 mmHg) in 5 of 7 cases. Conclusions We have developed a mathematical model capable of quantifying physiological parameters that reflect the severity of PH. PMID:26283577

CXCL12-CXCR4 signalling plays an essential role in proper patterning of aortic arch and pulmonary arteries.

PubMed

Kim, Bo-Gyeong; Kim, Yong Hwan; Stanley, Edward L; Garrido-Martin, Eva M; Lee, Young Jae; Oh, S Paul

2017-11-01

Chemokine CXCL12 (stromal derived factor 1: SDF1) has been shown to play important roles in various processes of cardiovascular development. In recent avian studies, CXCL12 signalling has been implicated in guidance of cardiac neural crest cells for their participation in the development of outflow tract and cardiac septum. The goal of this study is to investigate the extent to which CXCL12 signalling contribute to the development of aortic arch and pulmonary arteries in mammals. Novel Cxcl12-LacZ reporter and conditional alleles were generated. Using whole mount X-gal staining with the reporter allele and vascular casting techniques, we show that the domain branching pattern of pulmonary arteries in Cxcl12-null mice is completely disrupted and discordant with that of pulmonary veins and airways. Cxcl12-null mice also displayed abnormal and superfluous arterial branches from the aortic arch. The early steps of pharyngeal arch remodelling in Cxcl12-null mice appeared to be unaffected, but vertebral arteries were often missing and prominent aberrant arteries were present parallel to carotid arteries or trachea, similar to aberrant vertebral artery or thyroid ima artery, respectively. Analysis with computed tomography not only confirmed the results from vascular casting studies but also identified abnormal systemic arterial supply to lungs in the Cxcl12-null mice. Tie2-Cre mediated Cxcr4 deletion phenocopied the Cxcl12-null phenotypes, indicating that CXCR4 is the primary receptor for arterial patterning, whereas Cxcl12 or Cxcr4 deletion by Wnt1-Cre did not affect aortic arch patterning. CXCL12-CXCR4 signalling is essential for the correct patterning of aortic arches and pulmonary arteries during development. Superfluous arteries in Cxcl12-null lungs and the aortic arch infer a role of CXCL12 in protecting arteries from uncontrolled sprouting during development of the arterial system. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.

Heterochrony and early left-right asymmetry in the development of the cardiorespiratory system of snakes.

PubMed

van Soldt, Benjamin J; Metscher, Brian D; Poelmann, Robert E; Vervust, Bart; Vonk, Freek J; Müller, Gerd B; Richardson, Michael K

2015-01-01

Snake lungs show a remarkable diversity of organ asymmetries. The right lung is always fully developed, while the left lung is either absent, vestigial, or well-developed (but smaller than the right). A 'tracheal lung' is present in some taxa. These asymmetries are reflected in the pulmonary arteries. Lung asymmetry is known to appear at early stages of development in Thamnophis radix and Natrix natrix. Unfortunately, there is no developmental data on snakes with a well-developed or absent left lung. We examine the adult and developmental morphology of the lung and pulmonary arteries in the snakes Python curtus breitensteini, Pantherophis guttata guttata, Elaphe obsoleta spiloides, Calloselasma rhodostoma and Causus rhombeatus using gross dissection, MicroCT scanning and 3D reconstruction. We find that the right and tracheal lung develop similarly in these species. By contrast, the left lung either: (1) fails to develop; (2) elongates more slowly and aborts early without (2a) or with (2b) subsequent development of faveoli; (3) or develops normally. A right pulmonary artery always develops, but the left develops only if the left lung develops. No pulmonary artery develops in relation to the tracheal lung. We conclude that heterochrony in lung bud development contributes to lung asymmetry in several snake taxa. Secondly, the development of the pulmonary arteries is asymmetric at early stages, possibly because the splanchnic plexus fails to develop when the left lung is reduced. Finally, some changes in the topography of the pulmonary arteries are consequent on ontogenetic displacement of the heart down the body. Our findings show that the left-right asymmetry in the cardiorespiratory system of snakes is expressed early in development and may become phenotypically expressed through heterochronic shifts in growth, and changes in axial relations of organs and vessels. We propose a step-wise model for reduction of the left lung during snake evolution.

Heterochrony and Early Left-Right Asymmetry in the Development of the Cardiorespiratory System of Snakes

PubMed Central

van Soldt, Benjamin J.; Metscher, Brian D.; Poelmann, Robert E.; Vervust, Bart; Vonk, Freek J.; Müller, Gerd B.; Richardson, Michael K.

2015-01-01

Snake lungs show a remarkable diversity of organ asymmetries. The right lung is always fully developed, while the left lung is either absent, vestigial, or well-developed (but smaller than the right). A ‘tracheal lung’ is present in some taxa. These asymmetries are reflected in the pulmonary arteries. Lung asymmetry is known to appear at early stages of development in Thamnophis radix and Natrix natrix. Unfortunately, there is no developmental data on snakes with a well-developed or absent left lung. We examine the adult and developmental morphology of the lung and pulmonary arteries in the snakes Python curtus breitensteini, Pantherophis guttata guttata, Elaphe obsoleta spiloides, Calloselasma rhodostoma and Causus rhombeatus using gross dissection, MicroCT scanning and 3D reconstruction. We find that the right and tracheal lung develop similarly in these species. By contrast, the left lung either: (1) fails to develop; (2) elongates more slowly and aborts early without (2a) or with (2b) subsequent development of faveoli; (3) or develops normally. A right pulmonary artery always develops, but the left develops only if the left lung develops. No pulmonary artery develops in relation to the tracheal lung. We conclude that heterochrony in lung bud development contributes to lung asymmetry in several snake taxa. Secondly, the development of the pulmonary arteries is asymmetric at early stages, possibly because the splanchnic plexus fails to develop when the left lung is reduced. Finally, some changes in the topography of the pulmonary arteries are consequent on ontogenetic displacement of the heart down the body. Our findings show that the left-right asymmetry in the cardiorespiratory system of snakes is expressed early in development and may become phenotypically expressed through heterochronic shifts in growth, and changes in axial relations of organs and vessels. We propose a step-wise model for reduction of the left lung during snake evolution. PMID:25555231

Associations between thoracic radiographic changes and severity of pulmonary arterial hypertension diagnosed in 60 dogs via Doppler echocardiography: A retrospective study.

PubMed

Adams, Dustin S; Marolf, Angela J; Valdés-Martínez, Alejandro; Randall, Elissa K; Bachand, Annette M

2017-07-01

Doppler echocardiography is a noninvasive method for estimating and grading pulmonary arterial hypertension. No current literature associates significance of radiographic findings with severity of pulmonary arterial hypertension. We hypothesized that the number and conspicuity of radiographic findings suggestive of pulmonary arterial hypertension would be greater based on the severity of pulmonary arterial hypertension. Dogs with pulmonary arterial hypertension and normal control dogs were included in this retrospective, case control study. Three radiologists blinded to echocardiographic results scored thoracic radiographs for right ventricular and main pulmonary artery enlargement and pulmonary lobar artery enlargement, tortuosity, and blunting by multiple methods. Presence or absence of each finding was scored in an additive fashion and averaged for each grade of pulmonary arterial hypertension severity. Seventy-one dogs (60 dogs with pulmonary arterial hypertension and 11 control dogs) of which some had multiple studies were included: 20 mild, 21 moderate, 25 severe, and 11 absent pulmonary arterial hypertension. The following radiographic findings were significantly associated with increasing pulmonary arterial hypertension severity: right ventricular enlargement by "reverse D" and "3/5-2/5 cardiac ratio" methods, main pulmonary artery enlargement, and caudal lobar artery enlargement by the "3rd rib" method. Mean scores for severe pulmonary arterial hypertension and normal dogs were significantly different (P-value < 0.0001). Mean scores between different pulmonary arterial hypertension grades increased with severity but were not statistically significant. Individually and in combination, radiographic findings performed poorly in differentiating severity of pulmonary arterial hypertension. Findings indicated that thoracic radiographs should be utilized in conjunction with Doppler echocardiography in a complete diagnostic work-up for dogs with suspected pulmonary arterial hypertension. © 2017 American College of Veterinary Radiology.

Pulmonary vascular anomalies: a review of clinical and radiological findings of cases presenting with different complaints in childhood.

PubMed

Nacaroğlu, Hikmet Tekin; Ünsal-Karkıner, Canan Şule; Bahçeci-Erdem, Semiha; Özdemir, Rahmi; Karkıner, Aytaç; Alper, Hüdaver; Can, Demet

2016-01-01

Congenital pulmonary vascular abnormalities arise from several etiologies. These anomalies are difficult to categorize and sorted into distinct classifications. Major pulmonary vascular abnormalities can be ranked as interruption of the main pulmonary artery or its absence, emergence of the left pulmonary artery in the right pulmonary artery, pulmonary venous drainage abnormalities, and pulmonary arteriovenous malformations (PAVMs). Some of the cases are asymptomatic and diagnosed by coincidence, whereas a few of them are diagnosed by typical findings in the newborn and infancy period, symptoms, and radiological appearances. Early diagnosis is important, since death may occur as a result of pulmonary and cardiac pathologies developed in patients with pulmonary vascular anomalies. In this case presentation, the clinical and radiological findings of patients that presented with different complaints and were diagnosed with pulmonary vascular anomalies were introduced.

The development of a pseudo-chamber after balloon pulmonary angioplasty: long-term complications of balloon pulmonary angioplasty.

PubMed

Sugiyama, Hisashi; Kise, Hiroaki; Toda, Takako; Hoshiai, Minako

2016-11-01

We experienced a rare complication where extravasation developed a pseudo-chamber long after the balloon pulmonary angioplasty for supravalvular pulmonary stenosis. A 3-month-old girl was diagnosed with an anomalous origin of the left coronary artery from the pulmonary artery. She underwent the Takeuchi procedure at 10 months of age. During the follow-up, the supravalvular pulmonary stenosis deteriorated, and was treated by balloon pulmonary angioplasty with the double balloon technique catheter at 6 years of age. Angiography at the main pulmonary artery showed a small amount of extravasation contrast medium after the procedure. Follow-up echocardiography showed a diminished extravasation hemorrhage. Twelve years later, right ventricular enlargement due to pulmonary regurgitation had been observed on echocardiography. In addition, abnormal echo free space was detected at the left posterior of the left atrium. Enhanced computed tomography clearly demonstrated there was an orifice and extent of the pseudo-chamber. Surgical findings revealed a large tear just distal to the coronary tunnel. We speculated that extravasation blood was limited in the perivascular area early after the procedure but eventually reached the non-adhesive oblique pericardial sinus with age. Consequently, pulmonary to oblique pericardial sinus communication was established and looked like a pseudo-chamber long after the procedure. In conclusion, even if extravasation seems to be limited immediately after the balloon pulmonary angioplasty, it could expand for non-adhesive space and could develop a huge blood space like chamber. Long-term careful observation should be necessary for extravasation of pulmonary artery even with surgical adhesion.

[Total cavopulmonary connection for grown diminutive pulmonary artery after staged Blalock-Taussig shunt].

PubMed

Uchita, S; Matsuo, K; Ishida, T; Okajima, Y; Aotsuka, H; Fujiwara, T

1998-11-01

We report a two-year-old girl with asplenia, [A, L, L] DORV, pulmonary atresia, common AV valve, PDA, and TAPVC, who successfully underwent total cavo pulmonary connection (TCPC). Deep cyanosis was pointed out since birth. Cardiac catheterization performed on the sixth day after birth revealed a diminutive pulmonary artery tree of which PA index was 41 mm2/m2. Left modified Blalock-Taussig shunt was created at 27 days of age. The PA index increased to 282 mm2/mm2, but disparity in diameter between the left and the right pulmonary artery was yielded by PDA subsidence. Therefore additional contralateral B-T shunt was made at one year of age. Follow-up cardiac catheterization at 28 months of age showed well developed pulmonary artery; PA index of 460 mm2/m2, right pulmonary resistance (Rp) of 3.49 units, left Rp of 2.33 units, and estimated total Rp was 1.39. According to study, bidirectional Glenn procedure or TCPC was indicated. Considering necessity of urgent repair of common pulmonary vein obstruction, regurgitation of the common atrio-ventricular valve and pulmonary artery stenosis, TCPC was performed with concomitant repair of the associated lesions. Severe butterfly-figure stenosis of the central PA was augmented by anastomosing both the left SVC and the left-sided atrium. In conclusion, diminutive pulmonary artery could be adequately grown by phase-in Blalock-Taussig shunts. Pulmonary blood flow scintigraphy was thought to be useful for estimation of pulmonary resistance in such cases with different pulmonary resistance between right and left PA.

Histopathology of the great vessels in patients with pulmonary arterial hypertension in association with congenital heart disease: large pulmonary arteries matter too.

PubMed

Prapa, Matina; McCarthy, Karen P; Dimopoulos, Konstantinos; Sheppard, Mary N; Krexi, Dimitra; Swan, Lorna; Wort, S John; Gatzoulis, Michael A; Ho, Siew Yen

2013-10-03

Pulmonary arterial hypertension (PAH) is considered primarily a disease of the distal pulmonary arteries whereas little is known on the effect of long-standing pulmonary hypertension on the larger proximal pulmonary arteries. This study aims to investigate the structural changes in the great arteries of adults who developed PAH in association with congenital heart disease (CHD), with severe cases termed Eisenmenger syndrome. We performed macroscopic and light microscopy analyses on the great arteries of 10 formalin-fixed human hearts from patients with PAH/CHD and compared them to age-matched healthy controls. A detailed histology grading score was used to assess the severity of medial wall abnormalities. Severe atherosclerotic lesions were found macroscopically in the elastic pulmonary arteries of 4 PAH/CHD specimens and organised thrombi in 3; none were present in the controls. Significant medial wall abnormalities were present in the pulmonary trunk (PT), including fibrosis (80%), and atypical elastic pattern (80%). Cyst-like formations were present in less than one third of patients and were severe in a single case leading to wall rupture. The cumulative PT histology grading score was significantly higher in PAH/CHD cases compared to controls (p<0.0001) and correlated positively with larger PT diameters (ρ=0.812, p<0.0001) and the degree of medial wall hypertrophy (ρ=0.749, p<0.0001). Chronic PAH in association with CHD results in marked macroscopic and histological abnormalities in the large pulmonary arteries. These abnormalities are likely to affect haemodynamics and contribute to morbidity and mortality in this cohort. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Use of mathematic modeling to compare and predict hemodynamic effects of the modified Blalock-Taussig and right ventricle-pulmonary artery shunts for hypoplastic left heart syndrome.

PubMed

Bove, Edward L; Migliavacca, Francesco; de Leval, Marc R; Balossino, Rossella; Pennati, Giancarlo; Lloyd, Thomas R; Khambadkone, Sachin; Hsia, Tain-Yen; Dubini, Gabriele

2008-08-01

Stage one reconstruction (Norwood operation) for hypoplastic left heart syndrome can be performed with either a modified Blalock-Taussig shunt or a right ventricle-pulmonary artery shunt. Both methods have certain inherent characteristics. It is postulated that mathematic modeling could help elucidate these differences. Three-dimensional computer models of the Blalock-Taussig shunt and right ventricle-pulmonary artery shunt modifications of the Norwood operation were developed by using the finite volume method. Conduits of 3, 3.5, and 4 mm were used in the Blalock-Taussig shunt model, whereas conduits of 4, 5, and 6 mm were used in the right ventricle-pulmonary artery shunt model. The hydraulic nets (lumped resistances, compliances, inertances, and elastances) were identical in the 2 models. A multiscale approach was adopted to couple the 3-dimensional models with the circulation net. Computer simulations were compared with postoperative catheterization data. Good correlation was found between predicted and observed data. For the right ventricle-pulmonary artery shunt modification, there was higher aortic diastolic pressure, decreased pulmonary artery pressure, lower Qp/Qs ratio, and higher coronary perfusion pressure. Mathematic modeling predicted minimal regurgitant flow in the right ventricle-pulmonary artery shunt model, which correlated with postoperative Doppler measurements. The right ventricle-pulmonary artery shunt demonstrated lower stroke work and a higher mechanical efficiency (stroke work/total mechanical energy). The close correlation between predicted and observed data supports the use of mathematic modeling in the design and assessment of surgical procedures. The potentially damaging effects of a systemic ventriculotomy in the right ventricle-pulmonary artery shunt modification of the Norwood operation have not been analyzed.

Pulmonary arterial hypertension in children: diagnosis using ratio of main pulmonary artery to ascending aorta diameter as determined by multi-detector computed tomography.

PubMed

Caro-Domínguez, Pablo; Compton, Gregory; Humpl, Tilman; Manson, David E

2016-09-01

The ratio of the transverse diameter of the main pulmonary artery (MPA) to ascending aorta as determined at multi-detector CT is a tool that can be used to assess the pulmonary arterial size in cases of pulmonary arterial hypertension in children. To establish a ratio of MPA to ascending aorta diameter using multi-detector CT imaging suggestive of pulmonary arterial hypertension in children. We hypothesize that a defined ratio of MPA to ascending aorta is identifiable on multi-detector CT and that higher ratios can be used to reliably diagnose the presence of pulmonary arterial hypertension in children. We calculated the multi-detector CT ratio of MPA to ascending aorta diameter in 44 children with documented pulmonary arterial hypertension by right heart catheterization and in 44 age- and gender-matched control children with no predisposing factors for pulmonary arterial hypertension. We compared this multi-detector-CT-determined ratio with the MPA pressure in the study group, as well as with the ratio of MPA to ascending aorta in the control group. A threshold ratio value was calculated to accurately identify children with pulmonary arterial hypertension. Children with documented primary pulmonary arterial hypertension have a significantly higher ratio of MPA to ascending aorta (1.46) than children without pulmonary arterial hypertension (1.11). A ratio of 1.3 carries a positive likelihood of 34 and a positive predictive value of 97% for the diagnosis of pulmonary arterial hypertension. The pulmonary arteries were larger in children with pulmonary arterial hypertension than in a control group of normal children. A CT-measured ratio of MPA to ascending aorta of 1.3 should raise the suspicion of pulmonary arterial hypertension in children.

Development of occlusive neointimal lesions in distal pulmonary arteries of endothelin B receptor-deficient rats: a new model of severe pulmonary arterial hypertension.

PubMed

Ivy, D Dunbar; McMurtry, Ivan F; Colvin, Kelley; Imamura, Masatoshi; Oka, Masahiko; Lee, Dong-Seok; Gebb, Sarah; Jones, Peter Lloyd

2005-06-07

Human pulmonary arterial hypertension (PAH) is characterized by proliferation of vascular smooth muscle and, in its more severe form, by the development of occlusive neointimal lesions. However, few animal models of pulmonary neointimal proliferation exist, thereby limiting a complete understanding of the pathobiology of PAH. Recent studies of the endothelin (ET) system demonstrate that deficiency of the ET(B) receptor predisposes adult rats to acute and chronic hypoxic PAH, yet these animals fail to develop neointimal lesions. Herein, we determined and thereafter showed that exposure of ET(B) receptor-deficient rats to the endothelial toxin monocrotaline (MCT) leads to the development of neointimal lesions that share hallmarks of human PAH. The pulmonary hemodynamic and morphometric effects of 60 mg/kg MCT in control (MCT(+/+)) and ET(B) receptor-deficient (MCT(sl/sl)) rats at 6 weeks of age were assessed. MCT(sl/sl) rats developed more severe PAH, characterized by elevated pulmonary artery pressure, diminished cardiac output, and right ventricular hypertrophy. In MCT(sl/sl) rats, morphometric evaluation revealed the presence of neointimal lesions within small distal pulmonary arteries, increased medial wall thickness, and decreased arterial-to-alveolar ratio. In keeping with this, barium angiography revealed diminished distal pulmonary vasculature of MCT(sl/sl) rat lungs. Cells within neointimal lesions expressed smooth muscle and endothelial cell markers. Moreover, cells within neointimal lesions exhibited increased levels of proliferation and were located in a tissue microenvironment enriched with vascular endothelial growth factor, tenascin-C, and activated matrix metalloproteinase-9, factors already implicated in human PAH. Finally, assessment of steady state mRNA showed that whereas expression of ET(B) receptors was decreased in MCT(sl/sl) rat lungs, ET(A) receptor expression increased. Deficiency of the ET(B) receptor markedly accelerates the progression of PAH in rats treated with MCT and enhances the appearance of cellular and molecular markers associated with the pathobiology of PAH. Collectively, these results suggest an overall antiproliferative effect of the ET(B) receptor in pulmonary vascular homeostasis.

Development of Occlusive Neointimal Lesions in Distal Pulmonary Arteries of Endothelin B Receptor–Deficient Rats: A New Model of Severe Pulmonary Arterial Hypertension

PubMed Central

Ivy, D. Dunbar; McMurtry, Ivan F.; Colvin, Kelley; Imamura, Masatoshi; Oka, Masahiko; Lee, Dong-Seok; Gebb, Sarah; Jones, Peter Lloyd

2007-01-01

Background Human pulmonary arterial hypertension (PAH) is characterized by proliferation of vascular smooth muscle and, in its more severe form, by the development of occlusive neointimal lesions. However, few animal models of pulmonary neointimal proliferation exist, thereby limiting a complete understanding of the pathobiology of PAH. Recent studies of the endothelin (ET) system demonstrate that deficiency of the ETB receptor predisposes adult rats to acute and chronic hypoxic PAH, yet these animals fail to develop neointimal lesions. Herein, we determined and thereafter showed that exposure of ETB receptor–deficient rats to the endothelial toxin monocrotaline (MCT) leads to the development of neointimal lesions that share hallmarks of human PAH. Methods and Results The pulmonary hemodynamic and morphometric effects of 60 mg/kg MCT in control (MCT+/+) and ETB receptor–deficient (MCTsl/sl) rats at 6 weeks of age were assessed. MCTsl/sl rats developed more severe PAH, characterized by elevated pulmonary artery pressure, diminished cardiac output, and right ventricular hypertrophy. In MCTsl/sl rats, morphometric evaluation revealed the presence of neointimal lesions within small distal pulmonary arteries, increased medial wall thickness, and decreased arterial-to-alveolar ratio. In keeping with this, barium angiography revealed diminished distal pulmonary vasculature of MCTsl/sl rat lungs. Cells within neointimal lesions expressed smooth muscle and endothelial cell markers. Moreover, cells within neointimal lesions exhibited increased levels of proliferation and were located in a tissue microenvironment enriched with vascular endothelial growth factor, tenascin-C, and activated matrix metalloproteinase-9, factors already implicated in human PAH. Finally, assessment of steady state mRNA showed that whereas expression of ETB receptors was decreased in MCTsl/sl rat lungs, ETA receptor expression increased. Conclusions Deficiency of the ETB receptor markedly accelerates the progression of PAH in rats treated with MCT and enhances the appearance of cellular and molecular markers associated with the pathobiology of PAH. Collectively, these results suggest an overall antiproliferative effect of the ETB receptor in pulmonary vascular homeostasis. PMID:15927975

Pulmonary hypertension-"state of the art" management in 2012.

PubMed

Saxena, Anita

2012-01-01

Pulmonary artery hypertension (PAH) is a pathological condition of small pulmonary arteries, characterised by vascular proliferation and remodelling. The pulmonary artery pressure and pulmonary vascular resistance progressively rise, leading to right heart failure and death. Pulmonary artery hypertension may be secondary to various conditions, or it may be idiopathic where no underlying cause is identifiable. Earlier, only symptomatic treatment was available for such patients which did not change the natural history of the disease. However, over the years, improvement in understanding the pathogenesis has resulted in the development of targeted approaches to the treatment of PAH. Survival advantage has also been shown with some of the pharmacologic agents. This review article discusses the current management strategy for PAH with special emphasis on an idiopathic variety, in an Indian context. Copyright © 2012 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Nonenhanced MR angiography of the pulmonary arteries using single-shot radial quiescent-interval slice-selective (QISS): a technical feasibility study.

PubMed

Edelman, Robert R; Silvers, Robert I; Thakrar, Kiran H; Metzl, Mark D; Nazari, Jose; Giri, Shivraman; Koktzoglou, Ioannis

2017-06-30

For evaluation of the pulmonary arteries in patients suspected of pulmonary embolism, CT angiography (CTA) is the first-line imaging test with contrast-enhanced MR angiography (CEMRA) a potential alternative. Disadvantages of CTA include exposure to ionizing radiation and an iodinated contrast agent, while CEMRA is sensitive to respiratory motion and requires a gadolinium-based contrast agent. The primary goal of our technical feasibility study was to evaluate pulmonary arterial conspicuity using breath-hold and free-breathing implementations of a recently-developed nonenhanced approach, single-shot radial quiescent-interval slice-selective (QISS) MRA. Breath-hold and free-breathing, navigator-gated versions of radial QISS MRA were evaluated at 1.5 Tesla in three healthy subjects and 11 patients without pulmonary embolism or arterial occlusion by CTA. Images were scored by three readers for conspicuity of the pulmonary arteries through the level of the segmental branches. In addition, one patient with pulmonary embolism was imaged. Scan time for a 54-slice acquisition spanning the pulmonary arteries was less than 2 minutes for breath-hold QISS, and less than 3.4 min using free-breathing QISS. Pulmonary artery branches through the segmental level were conspicuous with either approach. Free-breathing scans showed only mild blurring compared with breath-hold scans. For both readers, less than 1% of pulmonary arterial segments were rated as "not seen" for breath-hold and navigator-gated QISS, respectively. In subjects with atrial fibrillation, single-shot radial QISS consistently depicted the pulmonary artery branches, whereas navigator-gated 3D balanced steady-state free precession showed motion artifacts. In one patient with pulmonary embolism, radial QISS demonstrated central pulmonary emboli comparably to CEMRA and CTA. The thrombi were highly conspicuous on radial QISS images, but appeared subtle and were not prospectively identified on scout images acquired using a single-shot bSSFP acquisition. In this technical feasibility study, both breath-hold and free-breathing single-shot radial QISS MRA enabled rapid, consistent demonstration of the pulmonary arteries through the level of the segmental branches, with only minimal artifacts from respiratory motion and cardiac arrhythmias. Based on these promising initial results, further evaluation in patients with suspected pulmonary embolism appears warranted.

Altered Redox Balance in the Development of Chronic Hypoxia-induced Pulmonary Hypertension.

PubMed

Jernigan, Nikki L; Resta, Thomas C; Gonzalez Bosc, Laura V

2017-01-01

Normally, the pulmonary circulation is maintained in a low-pressure, low-resistance state with little resting tone. Pulmonary arteries are thin-walled and rely heavily on pulmonary arterial distension and recruitment for reducing pulmonary vascular resistance when cardiac output is elevated. Under pathophysiological conditions, however, active vasoconstriction and vascular remodeling lead to enhanced pulmonary vascular resistance and subsequent pulmonary hypertension (PH). Chronic hypoxia is a critical pathological factor associated with the development of PH resulting from airway obstruction (COPD, sleep apnea), diffusion impairment (interstitial lung disease), developmental lung abnormalities, or high altitude exposure (World Health Organization [WHO]; Group III). The rise in pulmonary vascular resistance increases right heart afterload causing right ventricular hypertrophy that can ultimately lead to right heart failure in patients with chronic lung disease. PH is typically characterized by diminished paracrine release of vasodilators, antimitogenic factors, and antithrombotic factors (e.g., nitric oxide and protacyclin) and enhanced production of vasoconstrictors and mitogenic factors (e.g., reactive oxygen species and endothelin-1) from the endothelium and lung parenchyma. In addition, phenotypic changes to pulmonary arterial smooth muscle cells (PASMC), including alterations in Ca 2+ homeostasis, Ca 2+ sensitivity, and activation of transcription factors are thought to play prominent roles in the development of both vasoconstrictor and arterial remodeling components of hypoxia-associated PH. These changes in PASMC function are briefly reviewed in Sect. 1 and the influence of altered reactive oxygen species homeostasis on PASMC function discussed in Sects. 2-4.

Group 2 Pulmonary Hypertension: Pulmonary Venous Hypertension: Epidemiology and Pathophysiology.

PubMed

Clark, Craig B; Horn, Evelyn M

2016-08-01

Pulmonary hypertension from left heart disease (PH-LHD) is the most common form of PH, defined as mean pulmonary artery pressure ≥25 mm Hg and pulmonary artery wedge pressure ≥15 mm Hg. PH-LHD development is associated with more severe left-sided disease and its presence portends a poor prognosis, particularly once right ventricular failure develops. Treatment remains focused on the underlying LHD and despite initial enthusiasm for PH-specific therapies, most studies have been disappointing and their routine clinical use cannot be recommended. More work is urgently needed to better understand the pathophysiology underlying this disease and to develop effective therapeutic strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

Right ventricle performances with echocardiography and 99mTc myocardial perfusion imaging in pulmonary arterial hypertension patients.

PubMed

Liu, Jie; Fei, Lei; Huang, Guang-Qing; Shang, Xiao-Ke; Liu, Mei; Pei, Zhi-Jun; Zhang, Yong-Xue

2018-05-01

Right heart catheterization is commonly used to measure right ventricle hemodynamic parameters and is the gold standard for pulmonary arterial hypertension diagnosis; however, it is not suitable for patients' long-term follow-up. Non-invasive echocardiography and nuclear medicine have been applied to measure right ventricle anatomy and function, but the guidelines for the usefulness of clinical parameters remain to be established. The goal of this study is to identify reliable clinical parameters of right ventricle function in pulmonary arterial hypertension patients and analyze the relationship of these clinical parameters with the disease severity of pulmonary arterial hypertension. In this study, 23 normal subjects and 23 pulmonary arterial hypertension patients were recruited from January 2015 to March 2016. Pulmonary arterial hypertension patients were classified into moderate and severe pulmonary arterial hypertension groups according to their mean pulmonary arterial pressure levels. All the subjects were subjected to physical examination, chest X-ray, 12-lead electrocardiogram, right heart catheterization, two-dimensional echocardiography, and technetium 99m ( 99m Tc) myocardial perfusion imaging. Compared to normal subjects, the right heart catheterization indexes including right ventricle systolic pressure, right ventricle end diastolic pressure, pulmonary artery systolic pressure, pulmonary artery diastolic pressure, pulmonary vascular resistance, and right ventricle end systolic pressure increased in pulmonary arterial hypertension patients and were correlated with mean pulmonary arterial pressure levels. Echocardiography parameters, including tricuspid regurgitation peak velocity, tricuspid regurgitation pressure gradient, tricuspid annular plane systolic excursion and fractional area, right ventricle-myocardial performance index, were significantly associated with the mean pulmonary arterial pressure levels in pulmonary arterial hypertension patients. Furthermore, myocardial perfusion imaging was not observed in the normal subjects but in pulmonary arterial hypertension patients, especially severe pulmonary arterial hypertension subgroup, and showed potential diagnostic properties for pulmonary arterial hypertension. In conclusion, mean pulmonary arterial pressure levels are correlated with several right heart catheterization and echocardiography markers in pulmonary arterial hypertension patients; echocardiography and 99m Tc myocardial perfusion can be used to evaluate right ventricle performance in pulmonary arterial hypertension patients. Impact statement In this study, we analyzed the clinical parameters for evaluating RV function, including right ventricle catheterization (RHC), echocardiography, and technetium 99m ( 99m Tc) myocardial perfusion imaging (MPI) in normal Asian subjects and PAH patients ( n = 23 for each group). Our results demonstrated that six RHC indexes, four echocardiography indexes and MPI index were significantly altered in PAH patients and correlated with the levels of mean pulmonary arterial pressure. Importantly, we evaluated the diagnostic performance of MPI and found that MPI has a strong diagnostic accuracy in PAH patients. The findings from this study will be of interest to clinical investigators who make diagnosis and therapeutic strategies for PAH patients.

Pulmonary arterial hypertension in schistosomiasis.

PubMed

Gavilanes, Francisca; Fernandes, Caio J C; Souza, Rogerio

2016-09-01

Schistosomiasis is one of the most prevalent parasitic diseases in the world, being present in more than 70 countries. Pulmonary hypertension is one of the several chronic complications of schistosomiasis; particularly in developing countries, schistosomiasis-associated pulmonary arterial hypertension might represent one of the most prevalent causes of pulmonary arterial hypertension. New epidemiological data reinforce the importance of schistosomiasis in the context of pulmonary hypertension; furthermore, the inflammatory components of the pathophysiology of pulmonary hypertension associated with schistosomiasis have been recently explored, opening the perspective of new targets to be explored. Clinical and hemodynamic features of this particular complication of schistosomiasis, and the role of targeted therapies in this setting, have been better described in recent years. The importance of schistosomiasis-associated pulmonary hypertension is now recognized with better knowledge about its pathophysiology and management. Nevertheless, there is a need for better understanding the predisposal factors (genetic, environmental and so on) for the development of pulmonary hypertension in schistosomiasis as a way to prevent it from occurring. Furthermore, better control programs to decrease disease transmission are still missing, ensuring that we will have to face this devastating complication of schistosomiasis for a long future.

Wave Intensity Analysis Provides Novel Insights Into Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

PubMed

Su, Junjing; Manisty, Charlotte; Parker, Kim H; Simonsen, Ulf; Nielsen-Kudsk, Jens Erik; Mellemkjaer, Soren; Connolly, Susan; Lim, P Boon; Whinnett, Zachary I; Malik, Iqbal S; Watson, Geoffrey; Davies, Justin E; Gibbs, Simon; Hughes, Alun D; Howard, Luke

2017-10-31

In contrast to systemic hypertension, the significance of arterial waves in pulmonary hypertension (PH) is not well understood. We hypothesized that arterial wave energy and wave reflection are augmented in PH and that wave behavior differs between patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Right heart catheterization was performed using a pressure and Doppler flow sensor-tipped catheter to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery. Wave intensity analysis was subsequently applied to the acquired data. Ten control participants, 11 patients with PAH, and 10 patients with CTEPH were studied. Wave speed and wave power were significantly greater in PH patients compared with controls, indicating increased arterial stiffness and right ventricular work, respectively. The ratio of wave power to mean right ventricular power was lower in PAH patients than CTEPH patients and controls. Wave reflection index in PH patients (PAH: ≈25%; CTEPH: ≈30%) was significantly greater compared with controls (≈4%), indicating downstream vascular impedance mismatch. Although wave speed was significantly correlated to disease severity, wave reflection indexes of patients with mildly and severely elevated pulmonary pressures were similar. Wave reflection in the pulmonary artery increased in PH and was unrelated to severity, suggesting that vascular impedance mismatch occurs early in the development of pulmonary vascular disease. The lower wave power fraction in PAH compared with CTEPH indicates differences in the intrinsic and/or extrinsic ventricular load between the 2 diseases. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Transcatheter stenting of the right ventricular outflow tract augments pulmonary arterial growth in symptomatic infants with right ventricular outflow tract obstruction and hypercyanotic spells.

PubMed

McGovern, Eimear; Morgan, Conall T; Oslizlok, Paul; Kenny, Damien; Walsh, Kevin P; McMahon, Colin J

2016-10-01

We retrospectively reviewed all the children with right ventricular outflow tract obstruction, hypoplastic pulmonary annulus, and pulmonary arteries who underwent stenting of the right ventricular outflow tract for hypercyanotic spells at our institution between January, 2008 and December, 2013; nine patients who underwent cardiac catheterisation at a median age of 39 days (range 12-60 days) and weight of 3.6 kg (range 2.6-4.3 kg) were identified. The median number of stents placed was one stent (range 1-4). The median oxygen saturation increased from 60% to 96%. The median right pulmonary artery size increased from 3.3 to 5.5 mm (-2.68 to -0.92 Z-score), and the median left pulmonary artery size increased from 3.4 to 5.5 mm (-1.93 to 0 Z-scores). Among all, one patient developed transient pulmonary haemorrhage, and one patient had pericardial tamponade requiring drainage. Complete repair of tetralogy of Fallot +/- atrioventricular septal defect or double-outlet right ventricle was achieved in all nine patients. Transcatheter stent alleviation of the right ventricular outflow tract obstruction resolves hypercyanotic spells and allows reasonable growth of the pulmonary arteries to facilitate successful surgical repair. This represents a viable alternative to placement of a systemic-to-pulmonary artery shunt, particularly in small neonates.

Pulmonary arterial dissection in a post-partum patient with patent ductus arteriosus: Case report and review of the literature.

PubMed

Yaman, Mehmet; Arslan, Uğur; Ateş, Ahmet Hakan; Aksakal, Aytekin

2015-02-26

Pulmonary arterial dissection is an uncommon but usually a deadly complication of chronic pulmonary hypertension. A 26-year-old female patient was admitted to our clinics with sudden dyspnea and chest discomfort one hour after giving birth to twins by vaginal delivery. An echocardiography was performed with a pre-diagnosis of pulmonary embolism. However, echocardiographic examination revealed a dilated main pulmonary artery and a dissection flap extending from main pulmonary artery to left pulmonary artery. In summary, in this report, we described a very rare case of pulmonary artery dissection in a pregnant patient with a previously un-diagnosed patent ductus arteriosus without an obvious rise in pulmonary artery pressure and reviewed the relevant literature.

Nonmassive acute pulmonary embolism: evaluation of the impact of pulmonary arterial wall distensibility on the assessment of the CT obstruction score.

PubMed

Bigot, Julien; Rémy-Jardin, Martine; Duhamel, Alain; Gorgos, Andréi-Bogdan; Faivre, Jean-Baptiste; Rémy, Jacques

2010-02-01

To evaluate the impact of pulmonary arterial wall distensibility on the assessment of a computed tomography (CT) score in patients with nonmassive pulmonary embolism (PE) (ie, Mastora score). The arterial wall distensibility of five central pulmonary arteries (pulmonary artery trunk, right and left main pulmonary arteries, right and left interlobar pulmonary arteries) was studied on ECG-gated CT angiographic studies of the chest in 15 patients with no pulmonary arterial hypertension (group 1; mean pulmonary artery pressure: 17.2 mm Hg) and 9 patients with nonmassive PE (group 2), using 2D reconstructions at every 10% of the R-R interval. The systolic and diastolic reconstruction time windows of the examined arteries were identical in the 2 groups, obtained at 20% and 80% of the R-R interval, respectively. No statistically significant difference was observed between the mean values of the pulmonary arterial wall distensibility between the 2 groups, varying between 20.5% and 24% in group 1 and between 23.3% and 25.9% in group 2. The coefficients of variation of the average arterial surfaces were found to vary between 4.30% and 6.50% in group 1 and 4.2% and 8.4% in group 2. Except the pulmonary artery trunk in group 2, all the intraclass correlation coefficients were around 0.8 or greater than 0.8, that is the cutoff for good homogeneity of measurements. The pulmonary arterial wall systolic-diastolic distensibility does not interfere with the assessment of a CT obstruction score in the setting of nonmassive PE.

Pulmonary Hypertension

MedlinePlus

... together all groups are called pulmonary hypertension.) Group 1 Pulmonary Arterial Hypertension Group 1 PAH includes: PAH ... information, go to "Types of Pulmonary Hypertension." ) Group 1 Pulmonary Arterial Hypertension Group 1 pulmonary arterial hypertension ( ...

Beneficial Effects of Renal Denervation on Pulmonary Vascular Remodeling in Experimental Pulmonary Artery Hypertension.

PubMed

Qingyan, Zhao; Xuejun, Jiang; Yanhong, Tang; Zixuan, Dai; Xiaozhan, Wang; Xule, Wang; Zongwen, Guo; Wei, Hu; Shengbo, Yu; Congxin, Huang

2015-07-01

Activation of both the sympathetic nervous system and the renin-angiotensin-aldosterone system is closely associated with pulmonary arterial hypertension. We hypothesized that renal denervation decreases renin-angiotensin-aldosterone activity and inhibits the progression of pulmonary arterial hypertension. Twenty-two beagles were randomized into 3 groups. The dogs' pulmonary dynamics were measured before and 8 weeks after injection of 0.1mL/kg dimethylformamide (control dogs) or 2mg/kg dehydromonocrotaline (pulmonary arterial hypertension and pulmonary arterial hypertension + renal denervation dogs). Eight weeks after injection, neurohormone levels and pulmonary tissue morphology were measured. Levels of plasma angiotensin II and endothelin-1 were significantly increased after 8 weeks in the pulmonary arterial hypertension dogs and were higher in the lung tissues of these dogs than in those of the control and renal denervation dogs (mean [standard deviation] angiotensin II: 65 [9.8] vs 38 [6.7], 46 [8.1]; endothelin-1: 96 [10.3] vs 54 [6.2], 67 [9.4]; P < .01). Dehydromonocrotaline increased the mean pulmonary arterial pressure (16 [3.4] mmHg vs 33 [7.3] mmHg; P < .01), and renal denervation prevented this increase. Pulmonary smooth muscle cell proliferation was higher in the pulmonary arterial hypertension dogs than in the control and pulmonary arterial hypertension + renal denervation dogs. Renal denervation attenuates pulmonary vascular remodeling and decreases pulmonary arterial pressure in experimental pulmonary arterial hypertension. The effect of renal denervation may contribute to decreased neurohormone levels. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Pulmonary arterial dissection in a post-partum patient with patent ductus arteriosus: Case report and review of the literature

PubMed Central

Yaman, Mehmet; Arslan, Uğur; Ateş, Ahmet Hakan; Aksakal, Aytekin

2015-01-01

Pulmonary arterial dissection is an uncommon but usually a deadly complication of chronic pulmonary hypertension. A 26-year-old female patient was admitted to our clinics with sudden dyspnea and chest discomfort one hour after giving birth to twins by vaginal delivery. An echocardiography was performed with a pre-diagnosis of pulmonary embolism. However, echocardiographic examination revealed a dilated main pulmonary artery and a dissection flap extending from main pulmonary artery to left pulmonary artery. In summary, in this report, we described a very rare case of pulmonary artery dissection in a pregnant patient with a previously un-diagnosed patent ductus arteriosus without an obvious rise in pulmonary artery pressure and reviewed the relevant literature. PMID:25717357

A Mock Circulatory System Incorporating a Compliant 3D-Printed Anatomical Model to Investigate Pulmonary Hemodynamics.

PubMed

Knoops, Paul G M; Biglino, Giovanni; Hughes, Alun D; Parker, Kim H; Xu, Linzhang; Schievano, Silvia; Torii, Ryo

2017-07-01

A realistic mock circulatory system (MCS) could be a valuable in vitro testbed to study human circulatory hemodynamics. The objective of this study was to design a MCS replicating the pulmonary arterial circulation, incorporating an anatomically representative arterial model suitable for testing clinically relevant scenarios. A second objective of the study was to ensure the system's compatibility with magnetic resonance imaging (MRI) for additional measurements. A latex pulmonary arterial model with two generations of bifurcations was manufactured starting from a 3D-printed mold reconstructed from patient data. The model was incorporated into a MCS for in vitro hydrodynamic measurements. The setup was tested under physiological pulsatile flow conditions and results were evaluated using wave intensity analysis (WIA) to investigate waves traveling in the arterial system. Increased pulmonary vascular resistance (IPVR) was simulated as an example of one pathological scenario. Flow split between right and left pulmonary artery was found to be realistic (54 and 46%, respectively). No substantial difference in pressure waveform was observed throughout the various generations of bifurcations. Based on WIA, three main waves were identified in the main pulmonary artery (MPA), that is, forward compression wave, backward compression wave, and forward expansion wave. For IPVR, a rise in mean pressure was recorded in the MPA, within the clinical range of pulmonary arterial hypertension. The feasibility of using the MCS in the MRI scanner was demonstrated with the MCS running 2 h consecutively while acquiring preliminary MRI data. This study shows the development and verification of a pulmonary MCS, including an anatomically correct, compliant latex phantom. The setup can be useful to explore a wide range of hemodynamic questions, including the development of patient- and pathology-specific models, considering the ease and low cost of producing rapid prototyping molds, and the versatility of the setup for invasive and noninvasive (i.e., MRI) measurements. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

A Mock Circulatory System Incorporating a Compliant 3D-Printed Anatomical Model to Investigate Pulmonary Hemodynamics

PubMed Central

Knoops, Paul G.M.; Biglino, Giovanni; Hughes, Alun D.; Parker, Kim H.; Xu, Linzhang; Schievano, Silvia; Torii, Ryo

2017-01-01

A realistic mock circulatory system (MCS) could be a valuable in vitro testbed to study human circulatory hemodynamics. The objective of this study was to design a MCS replicating the pulmonary arterial circulation, incorporating an anatomically representative arterial model suitable for testing clinically relevant scenarios. A second objective of the study was to ensure the system's compatibility with magnetic resonance imaging (MRI) for additional measurements. A latex pulmonary arterial model with two generations of bifurcations was manufactured starting from a 3D-printed mold reconstructed from patient data. The model was incorporated into a MCS for in vitro hydrodynamic measurements. The setup was tested under physiological pulsatile flow conditions and results were evaluated using wave intensity analysis (WIA) to investigate waves traveling in the arterial system. Increased pulmonary vascular resistance (IPVR) was simulated as an example of one pathological scenario. Flow split between right and left pulmonary artery was found to be realistic (54 and 46%, respectively). No substantial difference in pressure waveform was observed throughout the various generations of bifurcations. Based on WIA, three main waves were identified in the main pulmonary artery (MPA), that is, forward compression wave, backward compression wave, and forward expansion wave. For IPVR, a rise in mean pressure was recorded in the MPA, within the clinical range of pulmonary arterial hypertension. The feasibility of using the MCS in the MRI scanner was demonstrated with the MCS running 2 h consecutively while acquiring preliminary MRI data. This study shows the development and verification of a pulmonary MCS, including an anatomically correct, compliant latex phantom. The setup can be useful to explore a wide range of hemodynamic questions, including the development of patient- and pathology-specific models, considering the ease and low cost of producing rapid prototyping molds, and the versatility of the setup for invasive and noninvasive (i.e., MRI) measurements. PMID:27925228

Pulmonary edema associated with upper airway obstruction in dogs.

PubMed

Algren, J T; Price, R D; Buchino, J J; Stremel, R W

1993-12-01

In order to evaluate the effect of acute upper airway obstruction upon pulmonary edema (PE) formation, we studied seven dogs that were subjected to inspiratory obstruction for three hours. Hypoxia was avoided by the administration of supplemental oxygen during the study period. Six dogs developed pulmonary vascular congestion, and four developed histologic findings of PE. Inspiratory intrapleural pressure decreased to -28 +/- 4 mmHg in dogs that developed PE and to -23 +/- 2 mmHg in dogs that did not. Transmural pulmonary artery pressure and pulmonary artery wedge pressure did not increase significantly. Central venous pressure during inspiration (CVPi) increased in all dogs, and CVP at end expiration (CVPe) was significantly higher in dogs with PE. Dogs that developed PE experienced a decrease in cardiac output and an increase in systemic vascular resistance. Furthermore, alveolar ventilation declined in dogs with PE, ultimately resulting in ventilatory failure. Pulmonary edema formation was not preceded by an increase in pulmonary vascular pressures but was associated with higher CVP, pulmonary vascular congestion, and hypercarbia.

A review of wave mechanics in the pulmonary artery with an emphasis on wave intensity analysis

PubMed Central

Su, Junjing; Hilberg, Ole; Howard, Luke; Simonsen, Ulf; Hughes, Alun D

2016-01-01

Mean pulmonary arterial pressure and pulmonary vascular resistance remain the most common hemodynamic measures to evaluate the severity and prognosis of pulmonary hypertension. However, pulmonary vascular resistance only captures the non-oscillatory component of the right ventricular hydraulic load and neglects the dynamic compliance of the pulmonary arteries and the contribution of wave transmission. Wave intensity analysis offers an alternative way to assess the pulmonary vasculature in health and disease. Wave speed is a measure of arterial stiffness and the magnitude and timing of wave reflection provide information on the degree of impedance mismatch between the proximal and distal circulation. Studies in the pulmonary artery have demonstrated distinct differences in arterial wave propagation between individuals with and without pulmonary vascular disease. Notably, greater wave speed and greater wave reflection are observed in patients with pulmonary hypertension and in animal models exposed to hypoxia. Studying wave propagation makes a valuable contribution to the assessment of the arterial system in pulmonary hypertension and here, we briefly review the current state of knowledge of the methods used to evaluate arterial waves in the pulmonary artery. PMID:27636734

Superior Vena Cava Stent Migration into the Pulmonary Artery Causing Fatal Pulmonary Infarction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anand, Girija, E-mail: gijanandm@hotmail.com; Lewanski, Conrad R.; Cowman, Steven A.

2011-02-15

Migration of superior vena cava (SVC) stents is a well-recognised complication of their deployment, and numerous strategies exist for their retrieval. To our knowledge, only three cases of migration of an SVC stent to the pulmonary vasculature have previously been reported. None of these patients developed complications that resulted in death. We report a case of SVC stent migration to the pulmonary vasculature with delayed pulmonary artery thrombosis and death from pulmonary infarction. We conclude that early retrieval of migrated stents should be performed to decrease the risk of serious complications.

Upregulated Copper Transporters in Hypoxia-Induced Pulmonary Hypertension

PubMed Central

Zimnicka, Adriana M.; Tang, Haiyang; Guo, Qiang; Kuhr, Frank K.; Oh, Myung-Jin; Wan, Jun; Chen, Jiwang; Smith, Kimberly A.; Fraidenburg, Dustin R.; Choudhury, Moumita S. R.; Levitan, Irena; Machado, Roberto F.; Kaplan, Jack H.; Yuan, Jason X.-J.

2014-01-01

Pulmonary vascular remodeling and increased arterial wall stiffness are two major causes for the elevated pulmonary vascular resistance and pulmonary arterial pressure in patients and animals with pulmonary hypertension. Cellular copper (Cu) plays an important role in angiogenesis and extracellular matrix remodeling; increased Cu in vascular smooth muscle cells has been demonstrated to be associated with atherosclerosis and hypertension in animal experiments. In this study, we show that the Cu-uptake transporter 1, CTR1, and the Cu-efflux pump, ATP7A, were both upregulated in the lung tissues and pulmonary arteries of mice with hypoxia-induced pulmonary hypertension. Hypoxia also significantly increased expression and activity of lysyl oxidase (LOX), a Cu-dependent enzyme that causes crosslinks of collagen and elastin in the extracellular matrix. In vitro experiments show that exposure to hypoxia or treatment with cobalt (CoCl2) also increased protein expression of CTR1, ATP7A, and LOX in pulmonary arterial smooth muscle cells (PASMC). In PASMC exposed to hypoxia or treated with CoCl2, we also confirmed that the Cu transport is increased using 64Cu uptake assays. Furthermore, hypoxia increased both cell migration and proliferation in a Cu-dependent manner. Downregulation of hypoxia-inducible factor 1α (HIF-1α) with siRNA significantly attenuated hypoxia-mediated upregulation of CTR1 mRNA. In summary, the data from this study indicate that increased Cu transportation due to upregulated CTR1 and ATP7A in pulmonary arteries and PASMC contributes to the development of hypoxia-induced pulmonary hypertension. The increased Cu uptake and elevated ATP7A also facilitate the increase in LOX activity and thus the increase in crosslink of extracellular matrix, and eventually leading to the increase in pulmonary arterial stiffness. PMID:24614111

New insights in the treatment strategy for pulmonary arterial hypertension.

PubMed

Sahara, Makoto; Takahashi, Toshiyuki; Imai, Yasushi; Nakajima, Toshiaki; Yao, Atsushi; Morita, Toshihiro; Hirata, Yasunobu; Nagai, Ryozo

2006-10-01

Recent advances in our understanding of the pathophysiological and molecular mechanisms involved in pulmonary arterial hypertension have led to the development of novel and rational pharmacological therapies. In addition to conventional therapy (i.e., supplemental oxygen and calcium channel blockers), prostacyclin or endothelin receptor antagonists have been recommended as a first-line therapy for pulmonary arterial hypertension. However, these treatments have potential limitations with regard to their long-term efficacy and improvement in survival. Furthermore, intravenous prostacyclin (epoprostenol) therapy, which is recommended by most experts for patients with New York Heart Association (NYHA) functional class IV, is complicated, uncomfortable for patients, and expensive because of the cumbersome administration system. Considering these circumstances, it is necessary to develop additional novel therapeutic approaches that target the various components of this multifactorial disease. In this short review, we present an overview of the current treatment options for pulmonary arterial hypertension and describe a case report with primary pulmonary hypertension. A male patient with NYHA functional class IV and showing no response to calcium channel blockers and prostacyclin exhibited significantly improved exercise tolerance and hemodynamics and long-term survival for more than 2.5 years after receiving an oral combination therapy of a phosphodiesterase type 5 inhibitor (sildenafil), phosphodiesterase type 3 inhibitor (pimobendan), and nicorandil. We also discuss the background and plausible potential mechanisms involved in this case, as well as future perspectives in the treatment of pulmonary arterial hypertension.

Change in pharmacological effect of endothelin receptor antagonists in rats with pulmonary hypertension: Role of ETB-receptor expression levels

PubMed Central

Sauvageau, Stéphanie; Thorin, Eric; Villeneuve, Louis; Dupuis, Jocelyn

2013-01-01

Background and purpose The endothelin (ET) system is activated in pulmonary arterial hypertension (PAH). The therapeutic value of pharmacological blockade of ET receptors has been demonstrated in various animal models and led to the current approval and continued development of these drugs for the therapy of human PAH. However, we currently incompletely comprehend what local modifications of this system occur as a consequence of PAH, particularly in small resistance arteries, and how this could affect the pharmacological response to ET receptor antagonists with various selectivities for the receptor subtypes. Therefore, the purposes of this study were to evaluate potential modifications of the pharmacology of the ET system in rat pulmonary resistance arteries from monocrotaline (MCT)-induced pulmonary arterial hypertension. Experimental approach ET-1 levels were quantified by ELISA. PreproET-1, ETA and ETB receptor mRNA expressions were quantified in pulmonary resistance arteries using Q-PCR, while protein expression was evaluated by Western blots. Reactivity to ET-1 of isolated pulmonary resistance arteries was measured in the presence of ETA (A-147627), ETB (A-192621) and dual ETA/B (bosentan) receptor antagonists. Key results In rats with PAH, plasma ET-1 increased (p < 0.001) while pulmonary levels were reduced (p < 0.05). In PAH arteries, preproET-1 (p < 0.05) and ETB receptor (p < 0.001) gene expressions were reduced, as were ETB receptor protein levels (p < 0.05). ET-1 induced similar vasoconstrictions in both groups. In arteries from sham animals, neither bosentan nor the ETA or the ETB receptor antagonists modified the response. In arteries from PAH rats, however, bosentan and the ETA receptor antagonist potently reduced the maximal contraction, while bosentan also reduced sensitivity (p < 0.01). Conclusions and implications The effectiveness of both selective ETA and dual ETA/B receptor antagonists is markedly increased in PAH. Down-regulation of pulmonary resistance arteries ETB receptor may contribute to this finding. PMID:19489130

Genetics Home Reference: pulmonary arterial hypertension

MedlinePlus

... Home Health Conditions Pulmonary arterial hypertension Pulmonary arterial hypertension Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Pulmonary arterial hypertension is a progressive disorder characterized by abnormally high ...

Left arm underdevelopment secondary to an isolated left subclavian artery in tetralogy of Fallot.

PubMed

Carnero Alcázar, Manuel; Marianeschi, Stefano; Ruiz Alonso, Enrique; García Torres, Enrique; Comas, Juan V

2010-02-01

The anomalous origin of the left subclavian artery is known to be associated with right aortic arch and tetralogy of Fallot. In our case, the left subclavian artery arose from the left pulmonary artery. Therefore, the left arm was perfused by poorly oxygenated blood from pulmonary arteries and some retrograde vertebral artery flow. Thus, the left arm was cyanotic and less developed than the right one. The patient underwent surgical repair with complete correction of tetralogy of Fallot and reimplantation of the left subclavian artery to the left carotid artery. 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

[The adrenergic mechanisms are involved in the pulmonary hemodynamics changes following experimental myocardial ischemia in rabbits].

PubMed

Evlakhov, V I; Poiasov, I Z

2012-05-01

In acute experiments in anesthetized rabbits the changes of the pulmonary hemodynamics following myocardial ischemia in the region of the descendent left coronary artery were studied in control animals and after the blockade of alpha-adrenoreceptors by phentolamine or N-cholinoreceptors of autonomic ganglia by hexamethonium. Following myocardial ischemia in control animals the pulmonary artery pressure and flow decreased, the pulmonary vascular resistance was elevated not significantly, the cardiac output decreased more than pulmonary artery flow. Following myocardial ischemia after the blockade of alpha-adrenoreceptors the pulmonary artery flow and cardiac output decreased in the same level and the pulmonary vascular resistance was decreased. In these conditions the pulmonary artery pressure decreased more than in control animals, meanwhile the pulmonary artery flow was decreased in the same level as in the last case. Following myocardial ischemia after the blockade of N-cholinoreceptors the pulmonary hemodynamics changes were the same as they were following myocardial ischemia in the control rabbits, the cardiac output decreased more than pulmonary artery flow. The disbalance of the cardiac output and pulmonary artery flow changes in the case of myocardial ischemia was caused by the pulmonary vessel reactions following activations of the humoral adrenergic mechanisms.

Pulmonary hypertension in hemodialysis patients without arteriovenous fistula: the effect of dialyzer composition.

PubMed

Kiykim, Ahmet Alper; Horoz, Mehmet; Ozcan, Turkay; Yildiz, Ibrahim; Sari, Sibel; Genctoy, Gultekin

2010-01-01

Pulmonary hypertension (PHT) increases mortality rate in hemodialysis (HD) patients. Numerous clinical, hemodynamic, and metabolic abnormalities have been suggested to be associated with the development of PHT in HD patients. We aimed to investigate the acute effects of two different dialyzer membranes on pulmonary arterial pressure (PAP) throughout a HD session in maintenance HD patients. Seventy-four HD patients dialyzed through permanent tunneled jugular central venous catheter were enrolled. A first-use cellulose acetate and high-flux polysulfone dialysis membrane were tested using a crossover design. For each membrane, pre- and post-dialysis pulmonary artery pressures were measured echocardiographically. Elevated pulmonary artery pressure was observed in 68.8% of patients (n = 51), whereas mild PHT was observed in 28.3% of patients (n = 21) and moderate PHT in 40.5% (n = 30). Decrease in pulmonary artery pressure following HD procedure performed using high-flux polysulfone membrane was significantly higher than the decrease observed following HD procedure performed using cellulose acetate membrane (p < 0.05). Significant decrease in pulmonary artery pressures was observed only after HD procedures performed using high-flux polysulfone membrane (p < 0.05). Ultrafiltered volume was only significantly correlated with the decrease in pulmonary artery pressure observed after HD procedure performed through high-flux polysulfone membrane (β = 0.411, p < 0.05). PHT seems to be prevalent among HD patients even in the absence of AV fistula and abnormal cardiac functions. Membrane composition seems to be important, which may overwhelm the improving effects of ultrafiltration.

Pulmonary hypertension

MedlinePlus

Pulmonary arterial hypertension; Sporadic primary pulmonary hypertension; Familial primary pulmonary hypertension; Idiopathic pulmonary arterial hypertension; Primary pulmonary hypertension; PPH; Secondary pulmonary ...

Lineage Analysis in Pulmonary Arterial Hypertension

DTIC Science & Technology

2013-06-01

monocrotaline pyrrole . The fate of lacZ-expressing cells will be correlated with immunofluorescent staining of endothelial marker CD31, mesenchymal marker...A) Pilot study: Time course of development of pulmonary hypertension in pneumonectomized mice injected with monocrotaline pyrrole (P/MCTP, n = 4... pyrrole . A, B) Normal muscular pulmonary artery (PA) adjacent to bronchiole (Br) A) hematoxylin and eosin stain (H&E), B) elastin-van Gieson stain (EVG

Unusual Systemic Artery to Pulmonary Artery Malformation Without Evidence of Systemic Disease, Trauma or Surgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geyik, Serdar; Yavuz, Kivilcim; Keller, Frederick S.

2006-10-15

Connections between the systemic and pulmonary arterial systems are rare conditions that can be due to either congenital or acquired diseases such as anomalous systemic arterial supply to normal lung, pulmonary sequestration, and systemic supply to pulmonary arteriovenous malformations. Herein, a unique case of systemic artery to pulmonary arterial malformation and its endovascular treatment in a patient with no history of the usual etiologies is reported.

Diabetes Mellitus Associates with Increased Right Ventricular Afterload and Remodeling in Pulmonary Arterial Hypertension.

PubMed

Whitaker, Morgan E; Nair, Vineet; Sinari, Shripad; Dherange, Parinita A; Natarajan, Balaji; Trutter, Lindsey; Brittain, Evan L; Hemnes, Anna R; Austin, Eric D; Patel, Kumar; Black, Stephen M; Garcia, Joe G N; Yuan Md PhD, Jason X; Vanderpool, Rebecca R; Rischard, Franz; Makino, Ayako; Bedrick, Edward J; Desai, Ankit A

2018-06-01

Diabetes mellitus is associated with left ventricular hypertrophy and dysfunction. Parallel studies have also reported associations between diabetes mellitus and right ventricular dysfunction and reduced survival in patients with pulmonary arterial hypertension. However, the impact of diabetes mellitus on the pulmonary vasculature has not been well characterized. We hypothesized that diabetes mellitus and hyperglycemia could specifically influence right ventricular afterload and remodeling in patients with Group I pulmonary arterial hypertension, providing a link to their known susceptibility to right ventricular dysfunction. Using an adjusted model for age, sex, pulmonary vascular resistance, and medication use, associations of fasting blood glucose, glycated hemoglobin, and the presence of diabetes mellitus were evaluated with markers of disease severity in 162 patients with pulmonary arterial hypertension. A surrogate measure of increased pulmonary artery stiffness, elevated pulmonary arterial elastance (P = .012), along with reduced log(pulmonary artery capacitance) (P = .006) were significantly associated with the presence of diabetes mellitus in patients with pulmonary arterial hypertension in a fully adjusted model. Similar associations between pulmonary arterial elastance and capacitance were noted with both fasting blood glucose and glycated hemoglobin. Furthermore, right ventricular wall thickness on echocardiography was greater in pulmonary arterial hypertension patients with diabetes, supporting the link between right ventricular remodeling and diabetes. Cumulatively, these data demonstrate that an increase in right ventricular afterload, beyond pulmonary vascular resistance alone, may influence right ventricular remodeling and provide a mechanistic link between the susceptibility to right ventricular dysfunction in patients with both diabetes mellitus and pulmonary arterial hypertension. Copyright © 2018 Elsevier Inc. All rights reserved.

A review of wave mechanics in the pulmonary artery with an emphasis on wave intensity analysis.

PubMed

Su, J; Hilberg, O; Howard, L; Simonsen, U; Hughes, A D

2016-12-01

Mean pulmonary arterial pressure and pulmonary vascular resistance (PVR) remain the most common haemodynamic measures to evaluate the severity and prognosis of pulmonary hypertension. However, PVR only captures the non-oscillatory component of the right ventricular hydraulic load and neglects the dynamic compliance of the pulmonary arteries and the contribution of wave transmission. Wave intensity analysis offers an alternative way to assess the pulmonary vasculature in health and disease. Wave speed is a measure of arterial stiffness, and the magnitude and timing of wave reflection provide information on the degree of impedance mismatch between the proximal and distal circulation. Studies in the pulmonary artery have demonstrated distinct differences in arterial wave propagation between individuals with and without pulmonary vascular disease. Notably, greater wave speed and greater wave reflection are observed in patients with pulmonary hypertension and in animal models exposed to hypoxia. Studying wave propagation makes a valuable contribution to the assessment of the arterial system in pulmonary hypertension, and here, we briefly review the current state of knowledge of the methods used to evaluate arterial waves in the pulmonary artery. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Pulmonary arterial hypertension in pregnancy.

PubMed

Običan, Sarah G; Cleary, Kirsten L

2014-08-01

Pulmonary hypertension is a medical condition characterized by elevated pulmonary arterial pressure and secondary right heart failure. Pulmonary arterial hypertension is a subset of pulmonary hypertension, which is characterized by an underlying disorder of the pulmonary arterial vasculature. Pulmonary hypertension can also occur secondarily to structural cardiac disease, autoimmune disorders, and toxic exposures. Although pregnancies affected by pulmonary hypertension and pulmonary arterial hypertension are rare, the pathophysiology exacerbated by pregnancy confers both high maternal and fetal mortality and morbidity. In light of new treatment modalities and the use of a multidisciplinary approach to care, maternal outcomes may be improving. Copyright © 2014 Elsevier Inc. All rights reserved.

Commercial air travel and in-flight pulmonary hypertension.

PubMed

Smith, Thomas G; Chang, Rae W; Robbins, Peter A; Dorrington, Keith L

2013-01-01

It has recently been shown that commercial air travel triggers hypoxic pulmonary vasoconstriction and modestly increases pulmonary artery pressure in healthy passengers. There is large interindividual variation in hypoxic pulmonary vasoreactivity, and some passengers may be at risk of developing flight-induced pulmonary hypertension, with potentially dangerous consequences. This study sought to determine whether it is possible for a susceptible passenger to develop pulmonary hypertension in response to a routine commercial flight. Using in-flight echocardiography, a passenger was studied during a 6-h commercial flight from London to Dubai. The passenger was generally well and frequently traveled by air, but had been diagnosed with Chuvash polycythemia, a genetic condition that is associated with increased hypoxic pulmonary vasoreactivity. Hematocrit had been normalized with regular venesection. During the flight, arterial oxygen saturation fell to a minimum of 96% and systolic pulmonary artery pressure (sPAP) rapidly increased into the pulmonary hypertensive range. The in-flight increase in sPAP was 50%, reaching a peak of 45 mmHg. This study has established that an asymptomatic but susceptible passenger can rapidly develop in-flight pulmonary hypertension even during a medium-haul flight. Prospective passengers at risk from such responses, including those who have cardiopulmonary disease or increased hypoxic pulmonary vasoreactivity, could benefit from preflight evaluation with a hypoxia altitude simulation test combined with simultaneous echocardiography (HAST-echo). The use of in-flight supplementary oxygen should be considered for susceptible individuals, including all patients diagnosed with Chuvash polycythemia.

Rarefaction and blood pressure in systemic and pulmonary arteries

PubMed Central

OLUFSEN, METTE S.; HILL, N. A.; VAUGHAN, GARETH D. A.; SAINSBURY, CHRISTOPHER; JOHNSON, MARTIN

2012-01-01

The effects of vascular rarefaction (the loss of small arteries) on the circulation of blood are studied using a multiscale mathematical model that can predict blood flow and pressure in the systemic and pulmonary arteries. We augmented a model originally developed for the systemic arteries (Olufsen et al. 1998, 1999, 2000, 2004) to (a) predict flow and pressure in the pulmonary arteries, and (b) predict pressure propagation along the small arteries in the vascular beds. The systemic and pulmonary arteries are modelled as separate, bifurcating trees of compliant and tapering vessels. Each tree is divided into two parts representing the `large' and `small' arteries. Blood flow and pressure in the large arteries are predicted using a nonlinear cross-sectional area-averaged model for a Newtonian fluid in an elastic tube with inflow obtained from magnetic resonance measurements. Each terminal vessel within the network of the large arteries is coupled to a vascular bed of small `resistance' arteries, which are modelled as asymmetric structured trees with specified area and asymmetry ratios between the parent and daughter arteries. For the systemic circulation, each structured tree represents a specific vascular bed corresponding to major organs and limbs. For the pulmonary circulation, there are four vascular beds supplied by the interlobar arteries. This manuscript presents the first theoretical calculations of the propagation of the pressure and flow waves along systemic and pulmonary large and small arteries. Results for all networks were in agreement with published observations. Two studies were done with this model. First, we showed how rarefaction can be modelled by pruning the tree of arteries in the microvascular system. This was done by modulating parameters used for designing the structured trees. Results showed that rarefaction leads to increased mean and decreased pulse pressure in the large arteries. Second, we investigated the impact of decreasing vessel compliance in both large and small arteries. Results showed, that the effects of decreased compliance in the large arteries far outweigh the effects observed when decreasing the compliance of the small arteries. We further showed that a decrease of compliance in the large arteries results in pressure increases consistent with observations of isolated systolic hypertension, as occurs in ageing. PMID:22962497

Variations of pulmonary arteries and other associated defects in Tetralogy of Fallot.

PubMed

Sheikh, Abdul Malik; Kazmi, Uzma; Syed, Najam Hyder

2014-01-01

The objective of study was to determine pulmonary artery variations and other associated cardiac defects in patients with Tetralogy of Fallot. This cross-sectional, descriptive study was carried out at The Children's Hospital and the Institute of Child Health, Lahore, from January 2006 to December 2012. All patients with Tetralogy of Fallot, who underwent cardiac catheterization during this period, were included. Standard cine-angiograms were done to record the pulmonary artery sizes and associated cardiac defects. A total of 576 patients with Tetralogy of Fallot were catheterized. Pulmonary Artery abnormalities were present in 109 (18.92%) patients. The commonest abnormality was isolated Left Pulmonary Artery stenosis (n = 60, 10.4%) followed by supra-valvular stenosis (n = 9, 1.6%). Left Pulmonary Artery was absent in seven patients(1.2%), while 1 patient (0.2%) had both absent right and left Pulmonary Arteries with segmental branch pulmonary arteries originating directly from Main Pulmonary Artery. Associated cardiac lesions included right aortic arch in 72 (12.5%), additional muscular Ventricular Septal Defect in 31 (5.4%), Patent Ductus Arteriosus in 31 (5.4%), bilateral Superior Vena Cava 36(6.2%), Atrial Septal Defect 4(0.7%) and Major Aortopulmonary Collateral Arteries in 75(13%) patients. Significant coronary artery abnormalities were present in 28(4.9%) children. Pulmonary artery abnormalities were present in 18.92% of patients with Tetralogy of Fallot. Isolated Left Pulmonary Artery origin stenosis was the most common abnormality. Significant associated cardiac lesions including Patent Ductus Arteriosus , additional muscular Ventricular Septal Defect, coronary artery abnormalities, bilateral Superior Vena Cava, Atrial Septal Defect and Major Aortopulmonary Collateral Arteries were present in one-third of the patients.

Acquired pulmonary artery stenosis in four dogs.

PubMed

Scansen, Brian A; Schober, Karsten E; Bonagura, John D; Smeak, Daniel D

2008-04-15

4 dogs with acquired pulmonary artery stenosis (PAS) were examined for various clinical signs. One was a mixed-breed dog with congenital valvular PAS that subsequently developed peripheral PAS, one was a Golden Retriever with pulmonary valve fibrosarcoma, one was a Pembroke Welsh Corgi in which the left pulmonary artery had inadvertently been ligated during surgery for correction of patent ductus arteriosus, and one was a Boston Terrier with a heart-base mass compressing the pulmonary arteries. All 4 dogs were evaluated with 2-dimensional and Doppler echocardiography to characterize the nature and severity of the stenoses; other diagnostic tests were also performed. The mixed-breed dog with valvular and peripheral PAS was euthanized, surgical resection of the pulmonic valve mass was performed in the Golden Retriever, corrective surgery was performed on the Pembroke Welsh Corgi with left pulmonary artery ligation, and the Boston Terrier with the heart-base mass was managed medically. Acquired PAS in dogs may manifest as a clinically silent heart murmur, syncope, or right-sided heart failure. The diagnosis is made on the basis of imaging findings, particularly results of 2-dimensional and Doppler echocardiography. Treatment may include surgical, interventional, or medical modalities and is targeted at resolving the inciting cause.

Supravalvular aortic stenosis after arterial switch operation.

PubMed

Maeda, Takuya; Koide, Masaaki; Kunii, Yoshifumi; Watanabe, Kazumasa; Kanzaki, Tomohito; Ohashi, Yuko

2016-07-01

Supravalvular aortic stenosis as a late complication of transposition of the great arteries is very rare, and only a few cases have been reported. We describe the case of a 14-year-old girl who developed supravalvular aortic stenosis as a late complication of the arterial switch operation for transposition of the great arteries. The narrowed ascending aorta was replaced with a graft. The right pulmonary artery was transected to approach the ascending aorta which adhered severely to the main pulmonary trunk, and we obtained a good operative field. © The Author(s) 2015.

Utility of computed tomography in assessment of pulmonary hypertension secondary to biomass smoke exposure

PubMed Central

Sertogullarindan, Bunyamin; Bora, Aydin; Yavuz, Alpaslan; Ekin, Selami; Gunbatar, Hulya; Arisoy, Ahmet; Avcu, Serhat; Ozbay, Bulent

2014-01-01

Background The aim of this study was to investigate the feasibility of main pulmonary artery diameter quantification by thoracic computerized tomography (CT) in the diagnosis of pulmonary hypertension seconder to biomass smoke exposure. Material/Methods One hundred and four women subjects with biomass smoke exposure and 20 healthy women subjects were enrolled in the prospective study. The correlation between echocardiographic estimation of systolic pulmonary artery pressure and the main pulmonary artery diameter of the cases were studied. Results The main pulmonary artery diameter was 26.9±5.1 in the control subjects and 37.1±6.4 in subjects with biomass smoke exposure. This difference was statistically significant (p<0.001). The systolic pulmonary artery pressure was 22.7±12.4 in the control subjects and 57.3±22 in subjects with biomass smoke exposure. This difference was statistically significant (p<0.001). Systolic pulmonary artery pressure was significantly correlated with the main pulmonary artery diameter (r=0.614, p<0.01). A receiver operating characteristic (ROC) curve analysis showed that a value of 29 mm of the main pulmonary artery diameter differentiated between pulmonary hypertension and non-pulmonary hypertension patients. The sensitivity of the measurement to diagnose pulmonary hypertension was 91% and specificity was 80%. Conclusions Our results indicate that main pulmonary artery diameter measurements by SCT may suggest presence of pulmonary hypertension in biomass smoke exposed women. PMID:24618994

Pulmonary damage following right ventricular outflow tachycardia ablation in a child: When electroanatomical mapping isn't good enough.

PubMed

Bansal, Neha; Kobayashi, Daisuke; Karpawich, Peter P

2017-11-11

A 14-year-old female was referred for severe pulmonary valve insufficiency after undergoing radiofrequency ablation for a right ventricular outflow tract tachycardia that originated in the proximal pulmonary artery at 10 years of age. Clinical records indicated that ablation was guided solely by electrograms and electroanatomical mapping. Due to myocardial tissue extensions, mapping failed to identify the level of the pulmonary valve annulus, which resulted in delivery of energy on the valve proper and into the pulmonary artery. She developed severe pulmonary valve insufficiency and moderate proximal pulmonary artery stenosis necessitating intravascular stent placement 4 years later with an associated transcatheter valve. Although the nonfluoroscopic approach during ablation has gained wide acceptance for use in children, this report highlights the benefits of adjunctive imaging to identify the precise location of the pulmonary valve when ablation therapy is contemplated in the right ventricle outflow tract. © 2017 Wiley Periodicals, Inc.

Development of a technique for determination of pulmonary artery pulse wave velocity in horses.

PubMed

Silva, Gonçalo Teixeira de Almeida; Guest, Bruce B; Gomez, Diego E; McGregor, Martine; Viel, Laurent; O'Sullivan, M Lynne; Runciman, John; Arroyo, Luis G

2017-05-01

Calcification of the tunica media of the axial pulmonary arteries (PA) has been reported in a large proportion of racehorses. In humans, medial calcification is a significant cause of arterial stiffening and is implicated in the pathogenesis of cardiac, cerebral, and renal microvascular diseases. Pulse wave velocity (PWV) provides a measure of arterial stiffness. This study aimed to develop a technique to determine PA-PWV in horses and, secondarily, to investigate a potential association between PA-PWV and arterial fibro-calcification. A dual-pressure sensor catheter (PSC) was placed in the main PA of 10 sedated horses. The pressure waves were used to determine PWV along the PA, using the statistical phase offset method. Histological analysis of the PA was performed to investigate the presence of fibro-calcified lesions. The mean (±SD) PWV was 2.3 ± 0.7 m/s in the proximal PA trunk and 1.1 ± 0.1 m/s further distal (15 cm) in a main PA branch. The mean (±SD) of mean arterial pressures in the proximal PA trunk was 30.1 ± 5.2 mmHg, and 22.0 ± 6.0 mmHg further distal (15 cm) within the main PA branch. The mean (±SD) pulse pressure in the proximal PA trunk was 15.0 ± 4.7 mmHg, and 13.5 ± 3.3 mmHg further distal (15 cm) within the main PA branch. Moderate to severe lesions of the tunica media of the PAs were observed in seven horses, but a correlation with PWV could not be established yet. Pulmonary artery PWV may be determined in standing horses. The technique described may allow further investigation of the effect of calcification of large PAs in the pathogenesis of equine pulmonary circulatory disorders. NEW & NOTEWORTHY Pulmonary artery pulse wave velocity was determined safely in standing sedated horses. The technique described may allow further investigation of the effect of calcification of large pulmonary arteries in the pathogenesis of pulmonary circulatory disorders in horses. Copyright © 2017 the American Physiological Society.

Pulmonary arterial remodeling induced by a Th2 immune response

PubMed Central

Daley, Eleen; Emson, Claire; Guignabert, Christophe; de Waal Malefyt, Rene; Louten, Jennifer; Kurup, Viswanath P.; Hogaboam, Cory; Taraseviciene-Stewart, Laimute; Voelkel, Norbert F.; Rabinovitch, Marlene; Grunig, Ekkehard; Grunig, Gabriele

2008-01-01

Pulmonary arterial remodeling characterized by increased vascular smooth muscle density is a common lesion seen in pulmonary arterial hypertension (PAH), a deadly condition. Clinical correlation studies have suggested an immune pathogenesis of pulmonary arterial remodeling, but experimental proof has been lacking. We show that immunization and prolonged intermittent challenge via the airways with either of two different soluble antigens induced severe muscularization in small- to medium-sized pulmonary arteries. Depletion of CD4+ T cells, antigen-specific T helper type 2 (Th2) response, or the pathogenic Th2 cytokine interleukin 13 significantly ameliorated pulmonary arterial muscularization. The severity of pulmonary arterial muscularization was associated with increased numbers of epithelial cells and macrophages that expressed a smooth muscle cell mitogen, resistin-like molecule α, but surprisingly, there was no correlation with pulmonary hypertension. Our data are the first to provide experimental proof that the adaptive immune response to a soluble antigen is sufficient to cause severe pulmonary arterial muscularization, and support the clinical observations in pediatric patients and in companion animals that muscularization represents one of several injurious events to the pulmonary artery that may collectively contribute to PAH. PMID:18227220

Ethyl pyruvate inhibits hypoxic pulmonary vasoconstriction and attenuates pulmonary artery cytokine expression

PubMed Central

Tsai, Ben M.; Lahm, Tim; Morrell, Eric D.; Crisostomo, Paul R.; Markel, Troy; Wang, Meijing; Meldrum, Daniel R.

2009-01-01

Hypoxic pulmonary vasoconstriction is a common consequence of acute lung injury and may be mediated by increased local production of proinflammatory cytokines. Ethyl pyruvate is a novel anti-inflammatory agent that has been shown to downregulate proinflammatory genes following hemorrhagic shock; however, its effects on hypoxic pulmonary vasoconstriction are unknown. We hypothesized that ethyl pyruvate would inhibit hypoxic pulmonary vasoconstriction and downregulate pulmonary artery cytokine expression during hypoxia. To study this, isometric force displacement was measured in isolated rat pulmonary artery rings (n=8/group) during hypoxia (95% N2/5% CO2) with or without prior ethyl pyruvate (10 mM) treatment. Following 60 minutes of hypoxia, pulmonary artery rings were analyzed for TNF-α and IL-1 mRNA via RT-PCR. Ethyl pyruvate inhibited hypoxic pulmonary artery contraction (4.49±2.32% vs. 88.80±5.68% hypoxia alone) and attenuated the hypoxic upregulation of pulmonary artery TNF and IL-1 mRNA (p<0.05). These data indicate that: 1) hypoxia increases pulmonary artery vasoconstriction and proinflammatory cytokine gene expression; 2) ethyl pyruvate decreases hypoxic pulmonary vasoconstriction and downregulates hypoxia-induced pulmonary artery proinflammatory cytokine gene expression; and 3) ethyl pyruvate may represent a novel therapeutic adjunct in the treatment of acute lung injury. PMID:17574585

Gene Therapy by Targeted Adenovirus-mediated Knockdown of Pulmonary Endothelial Tph1 Attenuates Hypoxia-induced Pulmonary Hypertension

PubMed Central

Morecroft, Ian; White, Katie; Caruso, Paola; Nilsen, Margaret; Loughlin, Lynn; Alba, Raul; Reynolds, Paul N; Danilov, Sergei M; Baker, Andrew H; MacLean, Margaret R

2012-01-01

Serotonin is produced by pulmonary arterial endothelial cells (PAEC) via tryptophan hydroxylase-1 (Tph1). Pathologically, serotonin acts on underlying pulmonary arterial cells, contributing to vascular remodeling associated with pulmonary arterial hypertension (PAH). The effects of hypoxia on PAEC-Tph1 activity are unknown. We investigated the potential of a gene therapy approach to PAH using selective inhibition of PAEC-Tph1 in vivo in a hypoxic model of PAH. We exposed cultured bovine pulmonary arterial smooth muscle cells (bPASMCs) to conditioned media from human PAECs (hPAECs) before and after hypoxic exposure. Serotonin levels were increased in hypoxic PAEC media. Conditioned media evoked bPASMC proliferation, which was greater with hypoxic PAEC media, via a serotonin-dependent mechanism. In vivo, adenoviral vectors targeted to PAECs (utilizing bispecific antibody to angiotensin-converting enzyme (ACE) as the selective targeting system) were used to deliver small hairpin Tph1 RNA sequences in rats. Hypoxic rats developed PAH and increased lung Tph1. PAEC-Tph1 expression and development of PAH were attenuated by our PAEC-Tph1 gene knockdown strategy. These results demonstrate that hypoxia induces Tph1 activity and selective knockdown of PAEC-Tph1 attenuates hypoxia-induced PAH in rats. Further investigation of pulmonary endothelial-specific Tph1 inhibition via gene interventions is warranted. PMID:22525513

Distinctive metabolomic fingerprint in scleroderma patients with pulmonary arterial hypertension.

PubMed

Deidda, Martino; Piras, Cristina; Cadeddu Dessalvi, Christian; Locci, Emanuela; Barberini, Luigi; Orofino, Susanne; Musu, Mario; Mura, Mario Nicola; Manconi, Paolo Emilio; Finco, Gabriele; Atzori, Luigi; Mercuro, Giuseppe

2017-08-15

Pulmonary arterial hypertension (PAH) in systemic sclerosis (SS) identifies a poor prognosis subset of patients. Recent studies suggested a "metabolic theory" on the development of pulmonary arterial hypertension. On this basis we performed a metabolomic study in order to evaluate whether differences in pulmonary arterial blood metabolites were identifiable in SS patients with increased pulmonary vascular resistance (PVR). We studied 18 SS patients (age 58.7±15.6years) free of pulmonary fibrosis who underwent a right heart catheterization (RHC). A blood sample was collected during the RHC in the distal peripheral circulation of the pulmonary arteries to perform the metabolomic analysis. Based on PVR we divided the population into Group A (n=8; PVR=1.16±0.23WU) and Group B (n=10; PVR=2.67±0.67WU; p<0.001 vs Group A). No significant differences were identified in terms of anthropometric, clinical, echo and therapeutic characteristics. At RHC the 2 groups showed a difference in mean pulmonary pressure values (Group A: 20±4mmHg; Group B: 27±3.4mmHg; p=0.03), with mild PAH in Group B. We applied an OSC-PLS-DA with a clear clusterization; SSc patients with PAH showed an increase in acetate, alanine, lactate, and lipoprotein levels and a decrease in γ-aminobutyrate, arginine, betaine, choline, creatine, creatinine, glucose, glutamate, glutamine, glycine, histidine, phenylalanine, and tyrosine levels CONCLUSIONS: Our results suggest that, despite similar clinical and disease-related parameters, SSc patients who develop PAH have an unfavorable metabolic profile able to cause an impaired production of metabolites with protective effects on endothelial cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of the Microcirculation in Chronic Thromboembolic Pulmonary Hypertension Patients: The Impact of Pulmonary Arterial Remodeling on Postoperative and Follow-Up Pulmonary Arterial Pressure and Vascular Resistance.

PubMed

Jujo, Takayuki; Sakao, Seiichiro; Ishibashi-Ueda, Hatsue; Ishida, Keiichi; Naito, Akira; Sugiura, Toshihiko; Shigeta, Ayako; Tanabe, Nobuhiro; Masuda, Masahisa; Tatsumi, Koichiro

2015-01-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is generally recognized to be caused by persistent organized thrombi that occlude the pulmonary arteries. The aim of this study was to investigate the characteristics of small vessel remodeling and its impact on the hemodynamics in CTEPH patients. Hemodynamic data were obtained from right heart catheterization in 17 CTEPH patients before pulmonary endarterectomy (PEA). Lung tissue specimens were obtained at the time of PEA. Pathological observations and evaluation of quantitative changes in pulmonary muscular arteries and veins were performed using light microscopy on 423 slides in 17 patients. The relationship between the results and the hemodynamics of CTEPH was investigated. Pulmonary arteriopathy and venopathy were recognized in most cases, although no plexiform lesions and no capillary-hemangiomatosis-like lesions were detected in any of the specimens. The severity of pulmonary arteriopathy was correlated with pulmonary vascular resistance (PVR) in the postoperative and follow-up periods. The PVR and mean pulmonary arterial pressure were significantly higher in the high-obstruction group than in the low-obstruction group. The findings in pulmonary venopathy were similar to the findings seen in pulmonary veno-occlusive disease in some cases, although severe venopathy was only observed in a portion of the pulmonary veins. There was a significant correlation between the extent of pulmonary arteriopathy and venopathy, although an effect of pulmonary venopathy to hemodynamics, including pulmonary arterial wedged pressure (PAWP), could not be identified. The vascular remodeling of the pulmonary muscular arteries was closely associated with the hemodynamics of CTEPH. Severe pulmonary arteriopathy might be related to residual pulmonary hypertension after PEA. Those altered pulmonary arteries might be a new target for the persistent PH after the operation.

Pulmonary artery segmentation and quantification in sickle cell associated pulmonary hypertension

NASA Astrophysics Data System (ADS)

Linguraru, Marius George; Mukherjee, Nisha; Van Uitert, Robert L.; Summers, Ronald M.; Gladwin, Mark T.; Machado, Roberto F.; Wood, Bradford J.

2008-03-01

Pulmonary arterial hypertension is a known complication associated with sickle-cell disease; roughly 75% of sickle cell disease-afflicted patients have pulmonary arterial hypertension at the time of death. This prospective study investigates the potential of image analysis to act as a surrogate for presence and extent of disease, and whether the size change of the pulmonary arteries of sickle cell patients could be linked to sickle-cell associated pulmonary hypertension. Pulmonary CT-Angiography scans from sickle-cell patients were obtained and retrospectively analyzed. Randomly selected pulmonary CT-Angiography studies from patients without sickle-cell anemia were used as negative controls. First, images were smoothed using anisotropic diffusion. Then, a combination of fast marching and geodesic active contours level sets were employed to segment the pulmonary artery. An algorithm based on fast marching methods was used to compute the centerline of the segmented arteries. From the centerline, the diameters at the pulmonary trunk and first branch of the pulmonary arteries were measured automatically. Arterial diameters were normalized to the width of the thoracic cavity, patient weight and body surface. Results show that the pulmonary trunk and first right and left pulmonary arterial branches at the pulmonary trunk junction are significantly larger in diameter with increased blood flow in sickle-cell anemia patients as compared to controls (p values of 0.0278 for trunk and 0.0007 for branches). CT with image processing shows great potential as a surrogate indicator of pulmonary hemodynamics or response to therapy, which could be an important tool for drug discovery and noninvasive clinical surveillance.

The value of dual-source multidetector-row computed tomography in determining pulmonary blood supply in patients with pulmonary atresia with ventricular septal defect.

PubMed

Chaosuwannakit, N; Makarawate, P

2018-01-01

Primary evaluation of patients with pulmonary atresia with ventricular septal defect (PA-VSD) traditionally relies upon echocardiography and conventional cardiac angiography (CCA). Cardiac angiography is considered the gold standard for delineation of anatomy in children with PA-VSD. Data comparing CCA and dual-source multidetector-row computed tomography angiography (MDCT) in PA-VSD patients is limited. The objective of this study was to test the hypothesis that MDCT is equivalent to CCA for anatomic delineation in these patients. Twenty-eight patients with PA-VSD underwent CCA and MDCT in close proximity to each other without interval therapy. A retrospective review of these 28 patients was performed. All MDCT data of pulmonary artery morphology, major aortopulmonary collateral arteries (MAPCAs) and type of blood supply (dual vs. single supply) were evaluated by blinded experts and results were compared with CCA. Twenty-eight patients had adequate size right and left pulmonary arteries (21 confluent and 7 non-confluent). Seven patients had complete absence of native pulmonary artery and 3 patients had stenosis of distal branches of pulmonary arteries; all had MAPCAs from descending thoracic aorta and/or subclavian arteries. Sensitivity, specificity, positive and negative predictive value of MDCT for detecting confluent of pulmonary arteries, absence of native pulmonary artery and stenosis of pulmonary arteries were all 100%. Moreover, accuracy of detecting MAPCAs was excellent. These results suggest that MDCT and CCA are equivalent in their ability to delineate pulmonary artery anatomy and MAPCAs. Dual source MDCT provides high diagnostic accuracy in evaluation of pulmonary blood supply in patients with PA-VSD and allows precise characterisation of the condition of pulmonary arteries and MAPCAs which is of paramount importance in managing patients with PA-VSD. (Folia Morphol 2018; 77, 1: 116-122).

Preceding bronchial cutting for exposure of the pulmonary artery buried in scar tissue after chemoradiotherapy.

PubMed

Nomori, Hiroaki; Cong, Yue; Sugimura, Hiroshi

2017-01-01

It is often difficult to expose the pulmonary artery buried in a scar tissue, especially in lung cancer patients that responded well to neoadjuvant chemoradiotherapy. Difficulty to access pulmonary artery branches may lead to potentially unnecessary pneumonectomy. To complete lobectomy in such cases, a technique with preceding bronchial cutting for exposure of the pulmonary artery is presented. After dissecting the pulmonary vein, the lobar bronchus is cut from the opposite side of the pulmonary artery with scissors. The back wall of the lobar bronchus is cut using a surgical knife from the luminal face, which can expose the pulmonary artery behind the bronchial stump and then complete lobectomy. Fourteen patients have been treated using the present technique, enabling complete resection by lobectomy (including sleeve lobectomy in 3 patients) without major bleeding. The present procedure can expose pulmonary artery buried in scar tissue, resulting in making the lobectomy safer.

Oxidative stress is associated with increased pulmonary artery systolic pressure in humans.

PubMed

Ghasemzadeh, Nima; Patel, Riyaz S; Eapen, Danny J; Veledar, Emir; Al Kassem, Hatem; Manocha, Pankaj; Khayata, Mohamed; Zafari, A Maziar; Sperling, Laurence; Jones, Dean P; Quyyumi, Arshed A

2014-06-01

Oxidative stress contributes to the development of pulmonary hypertension in experimental models, but this association in humans is unknown. We investigated the relationship between pulmonary artery systolic pressure measured by echocardiography and plasma aminothiol oxidative stress markers, with the hypothesis that oxidative stress will be higher in those with pulmonary hypertension. A group of 347 patients aged 65±12 years from the Emory Cardiovascular Biobank underwent echocardiographic assessment of left ventricular ejection fraction and pulmonary artery systolic pressure. Plasma aminothiols, cysteine, its oxidized form, cystine, glutathione, and its oxidized disulphide were measured and the redox potentials (Eh) of cysteine/cystine and glutathione/oxidized glutathione couples were calculated. Non-normally distributed variables were log transformed (Ln). Univariate predictors of pulmonary artery systolic pressure included age (P<0.001), sex (P=0.002), mitral regurgitation (P<0.001), left ventricular ejection fraction (P<0.001), left atrial size (P<0.001), diabetes mellitus (P=0.03), plasma Ln cystine (β=9.53; P<0.001), Ln glutathione (β=-5.4; P=0.002), and Eh glutathione (β=0.21; P=0.001). A multivariate linear regression model adjusting for all confounding variables demonstrated that Ln cystine (β=6.56; P=0.007), mitral regurgitation (β=4.52; P<0.001), statin use (β=-3.39; P=0.03), left ventricular ejection fraction (β=-0.26; P=0.003), and age (β=0.17; P=0.003) were independent predictors of pulmonary artery systolic pressure. For each 1% increase in plasma cystine, pulmonary artery systolic pressure increased by 16%. This association persisted in the subgroup with preserved left ventricular ejection fraction (≥50%) and no significant mitral regurgitation. Whether treatment of oxidative stress will improve pulmonary hypertension requires further study.

A method for evaluating the murine pulmonary vasculature using micro-computed tomography.

PubMed

Phillips, Michael R; Moore, Scott M; Shah, Mansi; Lee, Clara; Lee, Yueh Z; Faber, James E; McLean, Sean E

2017-01-01

Significant mortality and morbidity are associated with alterations in the pulmonary vasculature. While techniques have been described for quantitative morphometry of whole-lung arterial trees in larger animals, no methods have been described in mice. We report a method for the quantitative assessment of murine pulmonary arterial vasculature using high-resolution computed tomography scanning. Mice were harvested at 2 weeks, 4 weeks, and 3 months of age. The pulmonary artery vascular tree was pressure perfused to maximal dilation with a radio-opaque casting material with viscosity and pressure set to prevent capillary transit and venous filling. The lungs were fixed and scanned on a specimen computed tomography scanner at 8-μm resolution, and the vessels were segmented. Vessels were grouped into categories based on lumen diameter and branch generation. Robust high-resolution segmentation was achieved, permitting detailed quantitation of pulmonary vascular morphometrics. As expected, postnatal lung development was associated with progressive increase in small-vessel number and arterial branching complexity. These methods for quantitative analysis of the pulmonary vasculature in postnatal and adult mice provide a useful tool for the evaluation of mouse models of disease that affect the pulmonary vasculature. Copyright © 2016 Elsevier Inc. All rights reserved.

Partial anomalous left pulmonary artery: report of two cases and review of literature.

PubMed

Sen, Supratim; Winlaw, David S; Sholler, Gary F

2015-06-01

We describe two cases of anomalous origin of the left lower-lobe pulmonary artery from the right pulmonary artery. The primary diagnosis was mitral atresia, hypoplastic left ventricle, aortic arch hypoplasia in the first child, and tetralogy of Fallot in the second. In both cases, the pulmonary trunk gave rise to a left pulmonary artery in the normal position. In addition, a second branch of the left pulmonary artery arose from the right pulmonary artery, and passed posterior and inferior to the left main or upper-lobe bronchus to supply the left lower lobe. In this review, we compare our findings with previously reported examples of this extremely rare cardiac malformation, and discuss possible embryological explanations for the lesion.

Role of secretory phospholipase A(2) in rhythmic contraction of pulmonary arteries of rats with monocrotaline-induced pulmonary arterial hypertension.

PubMed

Tanabe, Yoshiyuki; Saito-Tanji, Maki; Morikawa, Yuki; Kamataki, Akihisa; Sawai, Takashi; Nakayama, Koichi

2012-01-01

Excessive stretching of the vascular wall in accordance with pulmonary arterial hypertension (PAH) induces a variety of pathogenic cellular events in the pulmonary arteries. We previously reported that indoxam, a selective inhibitor for secretory phospholipase A(2) (sPLA(2)), blocked the stretch-induced contraction of rabbit pulmonary arteries by inhibition of untransformed prostaglandin H(2) (PGH(2)) production. The present study was undertaken to investigate involvement of sPLA(2) and untransformed PGH(2) in the enhanced contractility of pulmonary arteries of experimental PAH in rats. Among all the known isoforms of sPLA(2), sPLA(2)-X transcript was most significantly augmented in the pulmonary arteries of rats with monocrotaline-induced pulmonary hypertension (MCT-PHR). The pulmonary arteries of MCT-PHR frequently showed two types of spontaneous contraction in response to stretch; 27% showed rhythmic contraction, which was sensitive to indoxam and SC-560 (selective COX-1 inhibitor), but less sensitive to NS-398 (selective COX-2 inhibitor); and 47% showed sustained incremental tension (tonic contraction), which was insensitive to indoxam and SC-560, but sensitive to NS-398 and was attenuated to 45% of the control. Only the rhythmically contracting pulmonary arteries of MCT-PHR produced a substantial amount of untransformed PGH(2), which was abolished by indoxam. These results suggest that sPLA(2)-mediated PGH(2) synthesis plays an important role in the rhythmic contraction of pulmonary arteries of MCT-PHR.

Homology of lungs and gas bladders: insights from arterial vasculature.

PubMed

Longo, Sarah; Riccio, Mark; McCune, Amy R

2013-06-01

Gas bladders of ray-finned fishes serve a variety of vital functions and are thus an important novelty of most living vertebrates. The gas bladder has long been regarded as an evolutionary modification of lungs. Critical evidence for this hypothesized homology is whether pulmonary arteries supply the gas bladder as well as the lungs. Pulmonary arteries, paired branches of the fourth efferent branchial arteries, deliver blood to the lungs in osteichthyans with functional lungs (lungfishes, tetrapods, and the ray-finned polypterid fishes). The fact that pulmonary arteries also supply the respiratory gas bladder of Amia calva (bowfin) has been used to support the homology of lungs and gas bladders, collectively termed air-filled organs (AO). However, the homology of pulmonary arteries in bowfin and lunged osteichthyans has been uncertain, given the apparent lack of pulmonary arteries in critical taxa. To re-evaluate the homology of pulmonary arteries in bowfin and lunged osteichthyans, we studied, using micro-CT technology, the arterial vasculature of Protopterus, Polypterus, Acipenser, Polyodon, Amia, and Lepisosteus, and analyzed these data using a phylogenetic approach. Our data reveal that Acipenser and Polyodon have paired posterior branches of the fourth efferent branchial arteries, which are thus similar in origin to pulmonary arteries. We hypothesize that these arteries are vestigial pulmonary arteries that have been coopted for new functions due to the dorsal shift of the AO and/or the loss of respiration in these taxa. Ancestral state reconstructions support pulmonary arteries as a synapomorphy of the Osteichthyes, provide the first concrete evidence for the retention of pulmonary arteries in Amia, and support thehomology of lungs and gas bladders due to a shared vascular supply. Finally, we use ancestral state reconstructions to show that arterial AO supplies from the celiacomesenteric artery or dorsal aorta appear to be convergent between teleosts and nonteleost actinopterygians. Copyright © 2013 Wiley Periodicals, Inc.

Dysregulated expression of microRNAs and mRNAs in pulmonary artery remodeling in ascites syndrome in broiler chickens

PubMed Central

Zhuang, Yu; Xiao, Qingyang; Cao, Huabin; Zhang, Caiying; Wang, Tiancheng; Lin, Huayuan; Guo, Xiaoquan; Hu, Guoliang

2017-01-01

Ascites syndrome (AS), also known as pulmonary artery hypertension, remains a challenging disease that severely affects both humans and broiler chickens. Pulmonary artery remodeling presents a key step in the development of AS. In this study, we obtained pulmonary artery tissues from broilers with and without AS to perform miRNA sequencing analysis, miRNA-mRNA association analysis and pathological examinations. 29 significantly differentially expressed miRNAs were found both in known and novel miRNAs with 18 up-regulated and 11 down-regulated miRNAs. Their predicted potential targets were involved in a wide range of functional clusters as indicated via GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses. The upregulation of miR-155, miR-23b-3p, miR-146b-5p and miR-146b-3p were found closely associated with the pathogenesis of pulmonary artery remodeling in AS progression. The association analysis for the miRNAs-mRNAs showed that these 29 significantly differentially expressed miRNAs regulate 162 differentially expressed target genes. Among them, 20 miRNAs correlated with 18 predicted target genes that appear to be involved in pulmonary artery remodeling, mainly in three broad physiological processes: the hypoxia sensing response (HIF1a, NHE1, STAT5 and STAT3), endothelial permeability dysfunction (CD44, TRAF2, CDK2AP1, LZTFL1, JAZF1, PEBP1, LRP1B, RPS14 and THBS2) and inflammation (MEOX2, STAT5, STAT3, IRF8, MAP3K8, IL-1BETA and TNFRSF1B). Pathological pulmonary artery remodeling in the AS broilers was consistently observed in the present study. Taken together, the current analysis further illuminates the molecular mechanism of pulmonary artery remodeling underlying AS progression. PMID:27791988

Opposing actions of TRPV4 channel activation in the lung vasculature.

PubMed

Ke, Sun-Kui; Chen, Lan; Duan, Hong-Bing; Tu, Yuan-Rong

2015-12-01

Transient receptor potential vanilloid 4 (TRPV4) calcium channels are known to promote endothelium-dependent relaxation of mouse mesenteric arteries but TRPV4's role in the pulmonary vasculature is uncertain. Thus, we characterized TRPV4 channel vascular tone regulation in mouse main pulmonary artery rings and in the isolated perfused pulmonary circulation and studied possible mechanisms behind these characterizations. Using myography and a TRPV4 specific agonist GSK1016790A in a C57BL/6 WT mouse model of isolated constant-flow lung perfusion, we studied vascular tone regulation in arterial rings from the main left and right pulmonary arteries and vascular resistance of the intra-pulmonary circulation beyond the second branches of the pulmonary arteries. Removal of the endothelium confirmed endothelial dependence. GSK1016790A relaxed the main pulmonary artery (EC50 4 × 10(-8)mol/L), which was inhibited by removal of the endothelium from main pulmonary artery rings. GSK1016790A significantly increased vascular resistance of the pulmonary circulation in isolated perfused lungs, but these effects were inhibited by a TRPV4 antagonist AB159908. A nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and K(+) channel blockers apamin plus charybdotoxin (ChTx) significantly inhibited GSK1016790A in the main pulmonary artery and in an isolated perfused lung in vitro. Activated TRPV4 channels increase pulmonary vascular resistance and vasodilate the main pulmonary artery. Copyright © 2015 Elsevier B.V. All rights reserved.

The long-term effects of arteriovenous fistula creation on the development of pulmonary hypertension in hemodialysis patients.

PubMed

Unal, Aydin; Tasdemir, Kutay; Oymak, Sema; Duran, Mustafa; Kocyigit, Ismail; Oguz, Fatih; Tokgoz, Bulent; Sipahioglu, Murat Hayri; Utas, Cengiz; Oymak, Oktay

2010-10-01

The aim of this prospective study was to evaluate long-term effects of arteriovenous fistula (AVF) on the development of pulmonary arterial hypertension (PAH) and the relationship between blood flow rate of AVF and pulmonary artery pressure (PAP) in the patients with end-stage renal disease (ESRD). This prospective study was performed in 20 patients with ESRD. Before an AVF was surgically created for hemodialysis, the patients were evaluated by echocardiography. Then, an AVF was surgically created in all patients. After mean 23.50 ± 2.25 months, the second evaluation was performed by echocardiography. Also, the blood flow rate of AVF was measured at the second echocardiographic evaluation. Pulmonary arterial hypertension was defined as a systolic PAP above 35 mmHg at rest. Mean age of 20 patients with ESRD was 55.05 ± 13.64 years; 11 of 20 patients were males. Pulmonary arterial hypertension was detected in 6 (30%) patients before AVF creation and in 4 (20%) patients after AVF creation. Systolic PAP value was meaningfully lower after AVF creation than before AVF creation (29.95 ± 10.26 mmHg vs. 35.35 ± 7.86 mmHg, respectively, P: 0.047). However, there was no significant difference between 2 time periods in terms of presence of PAH (P>0.05). Pulmonary artery pressure did not correlate with blood flow rate of AVF and duration after AVF creation (P>0.05). In hemodialysis patients, a surgically created AVF has no significant effect on the development of PAH within a long-term period. Similarly, blood flow rate of AVF also did not affect remarkably systolic PAP within the long-term period. © 2010 The Authors. Hemodialysis International © 2010 International Society for Hemodialysis.

Pulmonary artery pressure increases during commercial air travel in healthy passengers.

PubMed

Smith, Thomas G; Talbot, Nick P; Chang, Rae W; Wilkinson, Elizabeth; Nickol, Annabel H; Newman, David G; Robbins, Peter A; Dorrington, Keith L

2012-07-01

It is not known whether the mild hypoxia experienced by passengers during commercial air travel triggers hypoxic pulmonary vasoconstriction and increases pulmonary artery pressure in flight. Insidious pulmonary hypertensive responses could endanger susceptible passengers who have cardiopulmonary disease or increased hypoxic pulmonary vascular sensitivity. Understanding these effects may improve pre-flight assessment of fitness-to-fly and reduce in-flight morbidity and mortality. Eight healthy volunteers were studied during a scheduled commercial airline flight from London, UK, to Denver, CO. The aircraft was a Boeing 777 and the duration of the flight was 9 h. Systolic pulmonary artery pressure (sPAP) was assessed by portable Doppler echocardiography during the flight and over the following week in Denver, where the altitude (5280 ft/1610 m) simulates a commercial airliner environment. Cruising cabin altitude ranged between 5840 and 7170 ft (1780 to 2185 m), and mean arterial oxygen saturation was 95 +/- 0.6% during the flight. Mean sPAP increased significantly in flight by 6 +/- 1 mmHg to 33 +/- 1 mmHg, an increase of approximately 20%. After landing in Denver, sPAP was still 3 +/- 1 mmHg higher than baseline and remained elevated at 30 +/- 1 mmHg for a further 12 h. Pulmonary artery pressure increases during commercial air travel in healthy passengers, raising the possibility that hypoxic pulmonary hypertension could develop in susceptible individuals. A hypoxia altitude simulation test with simultaneous echocardiography ('HAST-echo') may be beneficial in assessing fitness to fly in vulnerable patients.

Inhibition of Notch3 prevents monocrotaline-induced pulmonary arterial hypertension.

PubMed

Zhang, Yonghong; Xie, Xinming; Zhu, Yanting; Liu, Lu; Feng, Wei; Pan, Yilin; Zhai, Cui; Ke, Rui; Li, Shaojun; Song, Yang; Fan, Yuncun; Fan, Fenling; Wang, Xiaochuang; Li, Fengjuan; Li, Manxiang

2015-01-01

It has been shown that activation of Notch3 signaling is involved in the development of pulmonary arterial hypertension (PAH) by stimulating pulmonary arteries remodeling, while the molecular mechanisms underlying this are still largely unknown. The aims of this study are to address these issues. Monocrotaline dramatically increased right ventricle systolic pressure to 39.0 ± 2.6 mmHg and right ventricle hypertrophy index to 53.4 ± 5.3% (P < 0.05 versus control) in rats, these were accompanied with significantly increased proliferation and reduced apoptosis of pulmonary vascular cells as well as pulmonary arteries remodeling. Treatment of PAH model with specific Notch inhibitor DAPT significantly reduced right ventricle systolic pressure to 26.6 ± 1.3 mmHg and right ventricle hypertrophy index to 33.5 ± 2.6% (P < 0.05 versus PAH), suppressed proliferation and enhanced apoptosis of pulmonary vascular cells as well as inhibited pulmonary arteries remodeling. Our results further indicated that level of Notch3 protein and NICD3 were increased in MCT-induced model of PAH, this was accompanied with elevation of Skp2 and Hes1 protein level and reduction of P27Kip1. Administration of rats with DAPT-prevented MCT induced these changes. Our results suggest that Notch3 signaling activation stimulated pulmonary vascular cells proliferation by Skp2-and Hes1-mediated P27Kip1 reduction, and Notch3 might be a new target to treat PAH.

Prenatal diagnosis of Berry syndrome by fetal echocardiography: a case report.

PubMed

Yang, Shui-Hua; Tian, Xiao-Xian; Li, Yuan-Yuan; Yang, Zuo-Jian

2016-10-01

We report a case in which Berry syndrome is diagnosed by fetal echocardiography. Fetal echocardiography showed that the ascending aorta, main pulmonary artery, left pulmonary artery, and right pulmonary artery were presented as a vascular complexity in the three vessels and pulmonary arterial branches view. © 2016, Wiley Periodicals, Inc.

Pulmonary artery dissection causing haemothorax in a cat: potential role of Dirofilaria immitis infection and literature review.

PubMed

Biasato, I; Tursi, M; Zanet, S; Longato, E; Capucchio, M T

2017-02-01

A 7-year-old male castrated domestic short-haired cat suddenly died. Gross examination revealed severe right-sided haemothorax with blood clots, four adult filarial nematodes in the blood clots and the caudal vena cava and haemorrhage dissecting into the tunica media of the right pulmonary artery. Histopathological investigation showed fibrosis of the tunica intima and disorganization/fragmentation of the elastic fibres accompanied by fibrous tissue deposition in the tunica media of both branches of pulmonary artery. Degenerative vasculopathy (intimal fibromuscular hyperplasia and medial hypertrophy/hyperplasia) involving pulmonary arteries was also observed. The polymerase chain reaction amplification and sequencing confirmed the identification of the parasite as Dirofilaria immitis. A diagnosis of pulmonary artery dissection with haemothorax and concomitant heartworm disease was formulated. Degenerative processes of the tunica media have been reported to cause pulmonary artery dissection in both humans and animals. Pulmonary artery remodelling induced by heartworms may be considered the underlying cause in the first case of feline pulmonary artery dissection, herein described. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of the Microcirculation in Chronic Thromboembolic Pulmonary Hypertension Patients: The Impact of Pulmonary Arterial Remodeling on Postoperative and Follow-Up Pulmonary Arterial Pressure and Vascular Resistance

PubMed Central

Ishida, Keiichi; Naito, Akira; Sugiura, Toshihiko; Shigeta, Ayako; Tanabe, Nobuhiro; Masuda, Masahisa; Tatsumi, Koichiro

2015-01-01

Background Chronic thromboembolic pulmonary hypertension (CTEPH) is generally recognized to be caused by persistent organized thrombi that occlude the pulmonary arteries. The aim of this study was to investigate the characteristics of small vessel remodeling and its impact on the hemodynamics in CTEPH patients. Methods and Results Hemodynamic data were obtained from right heart catheterization in 17 CTEPH patients before pulmonary endarterectomy (PEA). Lung tissue specimens were obtained at the time of PEA. Pathological observations and evaluation of quantitative changes in pulmonary muscular arteries and veins were performed using light microscopy on 423 slides in 17 patients. The relationship between the results and the hemodynamics of CTEPH was investigated. Pulmonary arteriopathy and venopathy were recognized in most cases, although no plexiform lesions and no capillary-hemangiomatosis-like lesions were detected in any of the specimens. The severity of pulmonary arteriopathy was correlated with pulmonary vascular resistance (PVR) in the postoperative and follow-up periods. The PVR and mean pulmonary arterial pressure were significantly higher in the high-obstruction group than in the low-obstruction group. The findings in pulmonary venopathy were similar to the findings seen in pulmonary veno-occlusive disease in some cases, although severe venopathy was only observed in a portion of the pulmonary veins. There was a significant correlation between the extent of pulmonary arteriopathy and venopathy, although an effect of pulmonary venopathy to hemodynamics, including pulmonary arterial wedged pressure (PAWP), could not be identified. Conclusion The vascular remodeling of the pulmonary muscular arteries was closely associated with the hemodynamics of CTEPH. Severe pulmonary arteriopathy might be related to residual pulmonary hypertension after PEA. Those altered pulmonary arteries might be a new target for the persistent PH after the operation. PMID:26252755

[The role of N-acetylcysteine against the injury of pulmonary artery induced by LPS].

PubMed

Huang, Xin-li; Ling, Yi-ling; Zhu, Tie-nian

2002-11-01

To investigate the alleviating effect of N-acetylcysteine (NAC) on lung injury induced by lipopolysaccharides (LPS) and its mechanism. The effects of NAC on changes of the pulmonary arterial reactivity and the ultrastructure of pulmonary arterial endothelium induced by LPS were observed with the isolated artery ring technique and scanning electron microscope (SEM). Malondialdehyde (MDA), nitric oxide (NO) contents and superoxide dismutase (SOD) activity of pulmonary artery tissues were detected. The exposure of pulmonary artery to LPS (4 microg/ml, 7 h) led to reduction of endothelium-dependent relaxation response to acetylcholine (ACh), which was reversed by the concomitant exposure to NAC (0.5 mmol/L, 7 h), whereas NAC itself had no effect on the response. Significant structural injury were observed under SEM in LPS group and alleviated the changes in LPS + NAC group. The MDA, NO contents increased but SOD activity decreased in LPS group, which were reversed by the concomitant exposure to NAC. NAC protects pulmonary artery endothelium and enhances endothelium-dependent relaxation response of pulmonary artery by antioxidation effect, which may be one of the mechanisms of its reversing pulmonary artery hypertension and following lung injury induced by LPS.

Interim prostacyclin therapy for an isolated disconnected pulmonary artery: a case report.

PubMed

Grech, Victor; Grixti, Cynthia

2010-06-02

Disconnected pulmonary arteries are unusual and may result in pulmonary hypertension with acute right heart failure. We report a case of a three-month-old Asian girl who presented with heart failure and severe pulmonary hypertension due to a disconnected right pulmonary artery. An epoprostenol (prostacyclin) infusion was instrumental in lowering pulmonary artery pressures and stabilizing the child prior to surgery. This is, to the best of our knowledge, the first report of successful prostacyclin usage in such a situation.

Superoxide differentially controls pulmonary and systemic vascular tone through multiple signalling pathways

PubMed Central

Snetkov, Vladimir A.; Smirnov, Sergey V.; Kua, Justin; Aaronson, Philip I.; Ward, Jeremy P.T.; Knock, Greg A.

2011-01-01

Aims The aim of this study was to determine the relative importance of Ca2+ sensitization, ion channels, and intracellular Ca2+ ([Ca2+]i) in the mixed constrictor/relaxation actions of superoxide anion on systemic and pulmonary arteries. Methods and results Pulmonary and mesenteric arteries were obtained from rat. Superoxide was generated in arteries and cells with 6-anilino-5,8-quinolinequinone (LY83583). Following pre-constriction with U46619, 10 μmol/L LY83583 caused constriction in pulmonary and relaxation in mesenteric arteries. Both constrictor and relaxant actions of LY83583 were inhibited by superoxide dismutase and catalase. LY83583 caused Rho-kinase-dependent constriction in α-toxin-permeabilized pulmonary but not mesenteric arteries. Phosphorylation of myosin phosphatase-targeting subunit-1 (MYPT-1; as determined by western blot), was enhanced by LY83583 in pulmonary artery only. However, in both artery types, changes in tension were closely correlated with changes in phosphorylation of the 20 kDa myosin light chain as well as changes in [Ca2+]i (as measured with Fura PE-3), with LY83583 causing increases in pulmonary and decreases in mesenteric arteries. When U46619 was replaced by 30 mmol/L K+, all changes in [Ca2+]i were abolished and LY83583 constricted both artery types. The KV channel inhibitor 4-aminopyridine abolished the LY83583-induced relaxation in mesenteric artery without affecting constriction in pulmonary artery. However, LY83583 caused a similar hyperpolarizing shift in the steady-state activation of KV current in isolated smooth muscle cells of both artery types. Conclusions Superoxide only causes Rho-kinase-dependent Ca2+ sensitization in pulmonary artery, resulting in constriction, and whilst it opens KV channels in both artery types, this only results in relaxation in mesenteric. PMID:20805095

Contribution of the bronchial circulation to lung preservation.

PubMed

LoCicero, J; Massad, M; Matano, J; Greene, R; Dunn, M; Michaelis, L L

1991-05-01

Short preservation time still severely limits lung transplantation. To determine the effect of bronchial arterial flush preservation, we studied 54 dogs using the isolated perfused working lung model. After baseline measurements, lungs were flushed with lactated Ringer's solution (60 ml/kg at 8 degrees C) by one of three methods: pulmonary artery perfusion, bronchial artery perfusion through a 15 cm closed aortic segment, or simultaneous pulmonary-bronchial artery perfusion. These groups were further subdivided and tested after 0, 4, and 17 hours of storage at 4 degrees C (n = 6 each). Lungs were ventilated (flow rate 140 ml/kg/min; inspired oxygen fraction 0.21) and continuously reperfused with normothermic deoxygenated autologous blood in a closed loop. Measured variables were hemodynamics, aerodynamics, and leukocytes in bronchoalveolar lavage. Survival time was determined from initial reperfusion to failure of the lung to oxygenate. After 0 and 4 hours of storage, there was no significant difference in survival times. After 17 hours, lungs subjected to pulmonary-bronchial artery perfusion survived longer than those perfused via either the pulmonary or bronchial arteries alone (120 +/- 24 versus 38 +/- 14 or 52 +/- 16 minutes; p less than 0.01). Pulmonary artery pressure and resistance in all groups except at failure were never different from baseline values in the intact animal. Shunts in the pulmonary-bronchial artery perfusion groups were closest to baseline at onset (8% +/- 4%) and remained lower throughout reperfusion than in the groups subjected to pulmonary or bronchial artery perfusion alone. After 17 hours, static compliance of pulmonary artery-perfused lungs was worse than baseline (1.1 +/- 0.2 x 10(-2) versus 3.2 +/- 0.7 x 10(-2) L/cm H2O/sec; p less than 0.05), whereas compliance in the pulmonary-bronchial artery perfusion groups remained constant (3.6 +/- 1.5 x 10(-2) L/cm H2O/sec). Elastic work performed by lungs subjected to pulmonary-bronchial artery flushing at onset was significantly lower when these lungs were reperfused immediately (201 +/- 14 versus 295 +/- 35 gm-m/min for pulmonary artery-flushed lungs) or after 4 hours of storage (229 +/- 30 versus 290 +/- 24 gm-m/min for pulmonary artery-flushed lungs). Bronchoalveolar lavage after 17 hours in the group subjected to pulmonary bronchial artery flushing demonstrated leukocyte counts similar to those of intact lungs (45 +/- 5 versus 29 +/- 8/mm3) and significantly less than in lungs subjected to pulmonary or bronchial artery flushing (137 +/- 18 or 82 +/- 10/mm3, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation

PubMed Central

Qureshi, M. Umar; Vaughan, Gareth D.A.; Sainsbury, Christopher; Johnson, Martin; Peskin, Charles S.; Olufsen, Mette S.; Hill, N.A.

2014-01-01

A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen and coworkers (Ottesen et al., 2003; Olufsen et al., 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of ‘large’ arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the ‘smaller’ arteries and veins of radii ≥ 50µm. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment of circulatory diseases within the lung. PMID:24610385

Anomalous right coronary artery arising from the pulmonary artery and constrictive pericarditis: an unusual association

PubMed Central

Silvestre, Odilson Marcos; Adam, Eduardo Leal; de Melo, Dirceu Thiago Pessoa; Dias, Ricardo Ribeiro; Ramires, Felix J. A.; Mady, Charles

2013-01-01

ABSTRACT The association of anomalous right coronary artery originating from the pulmonary artery and constrictive pericarditis has never been showed in the literature. We present the first case of this unusual association in a patient with right heart failure. After diagnosis, the patient was referred to surgery and underwent phrenic-to-phrenic pericardiectomy; graft implant of right internal thoracic artery to right coronary artery; and ligation of the anomalous origin of the right coronary artery from the pulmonary artery. Such procedures solved the potential risk of sudden death related to anomalous right coronary artery originating from the pulmonary artery and alleviated the symptoms of heart failure caused by constrictive pericarditis. PMID:24136766

Prenatal diagnosis of left pulmonary artery-to-pulmonary vein fistula and its successful surgical repair in a neonate.

PubMed

Ostras, Oleksii; Kurkevych, Andrii; Bohuta, Lyubomyr; Yalynska, Tetyana; Raad, Tammo; Lewin, Mark; Yemets, Illya

2015-04-01

Pulmonary arteriovenous fistula is a rare disease. To the best of our knowledge, prenatal diagnosis of a fistula between the left pulmonary artery and the left pulmonary vein has not been described in the medical literature. We report a case of the prenatal diagnosis of a left pulmonary artery-to-pulmonary vein fistula, followed by successful neonatal surgical repair.

Prenatal Diagnosis of Left Pulmonary Artery-to-Pulmonary Vein Fistula and Its Successful Surgical Repair in a Neonate

PubMed Central

Kurkevych, Andrii; Bohuta, Lyubomyr; Yalynska, Tetyana; Raad, Tammo; Lewin, Mark; Yemets, Illya

2015-01-01

Pulmonary arteriovenous fistula is a rare disease. To the best of our knowledge, prenatal diagnosis of a fistula between the left pulmonary artery and the left pulmonary vein has not been described in the medical literature. We report a case of the prenatal diagnosis of a left pulmonary artery-to-pulmonary vein fistula, followed by successful neonatal surgical repair. PMID:25873833

Challenges in the development of chronic pulmonary hypertension models in large animals

PubMed Central

Rothman, Abraham; Wiencek, Robert G.; Davidson, Stephanie; Evans, William N.; Restrepo, Humberto; Sarukhanov, Valeri; Mann, David

2017-01-01

Pulmonary hypertension (PH) results in significant morbidity and mortality. Chronic PH animal models may advance the study of PH’s mechanisms, evolution, and therapy. In this report, we describe the challenges and successes in developing three models of chronic PH in large animals: two models (one canine and one swine) utilized repeated infusions of ceramic microspheres into the pulmonary vascular bed, and the third model employed a surgical aorto-pulmonary shunt. In the canine model, seven dogs underwent microsphere infusions that resulted in progressive elevation of pulmonary arterial pressure over a few months. In this model, pulmonary endoarterial tissue was obtained for histology. In the aorto-pulmonary shunt swine model, 17 pigs developed systemic level pulmonary pressures after 2–3 months. In this model, pulmonary endoarterial tissue was sequentially obtained to assess for changes in gene and microRNA expression. In the swine microsphere infusion model, three pigs developed only a modest chronic increase in pulmonary arterial pressure, despite repeated infusions of microspheres (up to 40 in one animal). The main purpose of this model was for vasodilator testing, which was performed successfully immediately after acute microsphere infusions. Chronic PH in large animal models can be successfully created; however, a model’s characteristics need to match the investigational goals. PMID:28680575

Pedunculated Pulmonary Artery Sarcoma Suggested by Transthoracic Echocardiography.

PubMed

Wang, Xiaobing; Ren, Weidong; Yang, Jun

2016-04-01

Pulmonary artery sarcoma (PAS) is an extremely rare malignancy. It is usually found after it grows large enough to occupy almost the entire lumen of the pulmonary artery and causes serious clinical symptoms. Thus, it is usually difficult to distinguish PAS from pulmonary thromboembolism based on imaging examinations. Few case reports had shown the attachment of PAS to pulmonary artery, a key characteristic for diagnosis, and differential diagnosis of PAS. In this case, we found a PAS, which did not cause local obstruction and some tumor emboli, which obstructed the branches of the pulmonary arteries and caused pulmonary hypertension and clinical symptoms. Transthoracic echocardiography (TTE) revealed a part of the tumor attached to the intima of the main pulmonary artery with a peduncle and had obvious mobility, which was suggestive of PAS and differentiated it from the pulmonary thromboembolism. To our knowledge, this is the first case report of a pedunculated PAS suggested by TTE. Combined with pulmonary artery computed tomography angiography, the diagnosis of PAS is strongly suggested before the operation. This case indicates that TTE could reveal the attachment and mobility of PAS in the main pulmonary and may provide useful information for the diagnosis and differential diagnosis of PAS, especially a pedunculated PAS. © 2015, Wiley Periodicals, Inc.

Transferrin Receptor 1 in Chronic Hypoxia-Induced Pulmonary Vascular Remodeling.

PubMed

Naito, Yoshiro; Hosokawa, Manami; Sawada, Hisashi; Oboshi, Makiko; Hirotani, Shinichi; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Morisawa, Daisuke; Eguchi, Akiyo; Nishimura, Koichi; Soyama, Yuko; Fujii, Kenichi; Mano, Toshiaki; Ishihara, Masaharu; Tsujino, Takeshi; Masuyama, Tohru

2016-06-01

Iron is associated with the pathophysiology of several cardiovascular diseases, including pulmonary hypertension (PH). In addition, disrupted pulmonary iron homeostasis has been reported in several chronic lung diseases. Transferrin receptor 1 (TfR1) plays a key role in cellular iron transport. However, the role of TfR1 in the pathophysiology of PH has not been well characterized. In this study, we investigate the role of TfR1 in the development of hypoxia-induced pulmonary vascular remodeling. PH was induced by exposing wild-type (WT) mice and TfR1 hetero knockout mice to hypoxia for 4 weeks and evaluated via assessment of pulmonary vascular remodeling, right ventricular (RV) systolic pressure, and RV hypertrophy. In addition, we assessed the functional role of TfR1 in pulmonary artery smooth muscle cells in vitro. The morphology of pulmonary arteries did not differ between WT mice and TfR1 hetero knockout mice under normoxic conditions. In contrast, TfR1 hetero knockout mice exposed to 4 weeks hypoxia showed attenuated pulmonary vascular remodeling, RV systolic pressure, and RV hypertrophy compared with WT mice. In addition, the depletion of TfR1 by RNA interference attenuated human pulmonary artery smooth muscle cells proliferation induced by platelet-derived growth factor-BB (PDGF-BB) in vitro. These results suggest that TfR1 plays an important role in the development of hypoxia-induced pulmonary vascular remodeling. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Detection of patent ductus arteriosus with intraoperative transesophageal echocardiography in a patient undergoing closure of coronary artery to pulmonary artery fistula.

PubMed

Miyata, Yuka; Hayashi, Yukio

2017-01-01

Coronary artery to pulmonary artery fistula is an unusual vascular anomaly, and the shunt ratio of this fistula is usually small. We report anesthetic management of a 55-year-old female with annuloaortic ectasia, aortic valve regurgitation, and coronary artery to pulmonary artery fistula undergoing radical repair. We calculated the left-to-right shunt ratio after placement of a pulmonary artery catheter and found that the ratio was unexpectedly high. Thus, we explored the presence of another shunt by intraoperative transesophageal echocardiography and found patent ductus arteriosus undiagnosed before operation. A combination of a pulmonary artery catheter and transesophageal echocardiography is useful to explore the presence of another shunt, such as patent ductus arteriosus during anesthesia.

Update in pulmonary arterial hypertension.

PubMed

Mejía Chew, C R; Alcolea Batres, S; Ríos Blanco, J J

2016-11-01

Pulmonary arterial hypertension is a rare and progressive disease that mainly affects the pulmonary arterioles (precapillary), regardless of the triggering aetiology. The prevalence of pulmonary hypertension and pulmonary arterial hypertension in Spain is estimated at 19.2 and 16 cases per million inhabitants, respectively. The diagnosis of pulmonary arterial hypertension is based on haemodynamic criteria (mean pulmonary artery pressure ≥25mmHg, pulmonary capillary wedge pressure ≤15mmHg and pulmonary vascular resistance >3 Wood units) and therefore requires the implementation of right cardiac catheterisation. Sequential therapy with a single drug has been used in clinical practice. However, recent European guidelines recommend combined initial therapy in some situations. This review conducts a critical update of our knowledge of this disease according to the latest guidelines and recommendations. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Interim prostacyclin therapy for an isolated disconnected pulmonary artery: a case report

PubMed Central

2010-01-01

Introduction Disconnected pulmonary arteries are unusual and may result in pulmonary hypertension with acute right heart failure. Case presentation We report a case of a three-month-old Asian girl who presented with heart failure and severe pulmonary hypertension due to a disconnected right pulmonary artery. An epoprostenol (prostacyclin) infusion was instrumental in lowering pulmonary artery pressures and stabilizing the child prior to surgery. Conclusions This is, to the best of our knowledge, the first report of successful prostacyclin usage in such a situation. PMID:20525186

Three-dimensional segmentation of pulmonary artery volume from thoracic computed tomography imaging

NASA Astrophysics Data System (ADS)

Lindenmaier, Tamas J.; Sheikh, Khadija; Bluemke, Emma; Gyacskov, Igor; Mura, Marco; Licskai, Christopher; Mielniczuk, Lisa; Fenster, Aaron; Cunningham, Ian A.; Parraga, Grace

2015-03-01

Chronic obstructive pulmonary disease (COPD), is a major contributor to hospitalization and healthcare costs in North America. While the hallmark of COPD is airflow limitation, it is also associated with abnormalities of the cardiovascular system. Enlargement of the pulmonary artery (PA) is a morphological marker of pulmonary hypertension, and was previously shown to predict acute exacerbations using a one-dimensional diameter measurement of the main PA. We hypothesized that a three-dimensional (3D) quantification of PA size would be more sensitive than 1D methods and encompass morphological changes along the entire central pulmonary artery. Hence, we developed a 3D measurement of the main (MPA), left (LPA) and right (RPA) pulmonary arteries as well as total PA volume (TPAV) from thoracic CT images. This approach incorporates segmentation of pulmonary vessels in cross-section for the MPA, LPA and RPA to provide an estimate of their volumes. Three observers performed five repeated measurements for 15 ex-smokers with ≥10 pack-years, and randomly identified from a larger dataset of 199 patients. There was a strong agreement (r2=0.76) for PA volume and PA diameter measurements, which was used as a gold standard. Observer measurements were strongly correlated and coefficients of variation for observer 1 (MPA:2%, LPA:3%, RPA:2%, TPA:2%) were not significantly different from observer 2 and 3 results. In conclusion, we generated manual 3D pulmonary artery volume measurements from thoracic CT images that can be performed with high reproducibility. Future work will involve automation for implementation in clinical workflows.

Tamoxifen Therapy to Treat Pulmonary Arterial Hypertension

ClinicalTrials.gov

2018-05-16

Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Primary Pulmonary Hypertension; Lung Diseases; Tamoxifen; Estrogen Receptor Antagonist; Hormone Antagonists; Estrogens

Effect of hypothermic pulmonary artery flushing on capillary filtration coefficient.

PubMed

Andrade, R S; Wangensteen, O D; Jo, J K; Tsai, M Y; Bolman, R M

2000-07-27

We previously demonstrated that surfactant dilution and inhibition occur immediately after pulmonary artery flushing with hypothermic modified Euro-Collins solution. Consequently, we speculated that increased capillary permeability contributed to these surfactant changes. To test this hypothesis, we evaluated the effects of hypothermic pulmonary artery flushing on the pulmonary capillary filtration coefficient (Kfc), and additionally performed a biochemical analysis of surfactant. We used a murine isolated, perfused lung model to measure the pulmonary capillary filtration coefficient and hemodynamic parameters, to determine the wet to dry weight ratio, and to evaluate surfactant by biochemical analysis of lung lavage fluid. We defined three study groups. In group I (controls), we harvested lungs without hypothermic pulmonary artery flushing, and measured Kfc immediately. In group II (in situ flush), we harvested lungs after hypothermic pulmonary artery flushing with modified Euro-Collins solution, and then measured Kfc. Experiments in groups I and II were designed to evaluate persistent changes in Kfc after pulmonary artery flushing. In group III (ex vivo flush), we flushed lungs ex vivo to evaluate transient changes in Kfc during hypothermic pulmonary artery flushing. Groups I and II did not differ significantly in capillary filtration coefficient and hemodynamics. Group II showed significant alterations on biochemical surfactant analysis and a significant increase in wet-to-dry weight ratio, when compared with group I. In group III, we observed a significant transient increase in capillary filtration coefficient during pulmonary artery flushing. Hypothermic pulmonary artery flushing transiently increases the capillary filtration coefficient, leads to an increase in the wet to dry weight ratio, and induces biochemical surfactant changes. These findings could be explained by the effects of hypothermic modified Euro-Collins solution on pulmonary capillary permeability.

[Aerosolized iloprost therapy for pulmonary hypertensive crisis in 4 patients with idiopathic pulmonary arterial hypertension].

PubMed

Deng, Ke-wu; Zhou, Yu-jie; Xu, Xi-qi; Wu, Ming-ying; Wang, Guo-hong; Bian, Hong; Chen, Bo; Wang, Chun-bo

2012-10-01

To summary the efficacy and safety of aerosolized iloprost in patients with pulmonary hypertensive crisis. On the basis of conventional therapy, aerosolized iloprost (10 µg per time for 10 - 15 min in 2 hours interval, 8 times per day) was administered to four patients with idiopathic pulmonary arterial hypertension and pulmonary hypertensive crisis. Blood pressure, heart rate, systemic artery oxygen saturation, systolic pulmonary arterial pressure (sPAP) measured by echocardiography and the adverse events were analyzed. After aerosolized iloprost therapy, sPAP was significantly decreased and systemic artery oxygen saturation was improved. Adverse events (nausea, vomiting, diarrhea, dry cough) were observed in two patients, and the iloprost use was stopped in one patient due to severe vomiting and diarrhea. Aerosolized iloprost could significantly reduce the sPAP and improve the systemic artery oxygen saturation in patients with pulmonary hypertension crisis.

Continuous inhaled iloprost in a neonate with d-transposition of the great arteries and severe pulmonary arterial hypertension.

PubMed

Dykes, John C; Torres, Marilyn; Alexander, Plato J

2016-03-01

This report describes the case of a neonate with d-transposition of the great arteries and severe pulmonary arterial hypertension stabilised in the post-operative period with continuous iloprost nebulisation. To our knowledge, this is the first documented method of treating post-operative severe pulmonary arterial hypertension with continuous inhaled iloprost in a patient with complex CHD. We found this method of delivering the drug very effective in stabilising haemodynamic swings in the setting of severe pulmonary arterial hypertension.

Platelets in pulmonary vascular physiology and pathology

PubMed Central

Kroll, Michael H.; Afshar-Kharghan, Vahid

2012-01-01

Almost a trillion platelets pass through the pulmonary circulation every minute, yet little is known about how they support pulmonary physiology or contribute to the pathogenesis of lung diseases. When considering this conundrum, three questions jump out: Does platelet production in the lungs occur? Why does severe thrombocytopenia—which undercuts the principal physiological role of platelets to effect hemostasis—not lead to pulmonary hemorrhage? Why does atherothrombosis—which platelets initiate, maintain, and trigger is other critically important arterial beds—not develop in the pulmonary artery? The purpose of this review is to explore these and derivative questions by providing data within a conceptual framework that begins to organize a subject that is largely unassembled. PMID:23130099

Aggressive Surgical Resection of Pulmonary Artery Intimal Sarcoma.

PubMed

Yamamoto, Yoko; Shintani, Yasushi; Funaki, Soichiro; Taira, Masaki; Ueno, Takayoshi; Kawamura, Tomohiro; Kanzaki, Ryu; Minami, Masato; Sawa, Yoshiki; Okumura, Meinoshin

2018-05-03

Intimal sarcoma of the pulmonary artery is a rare and highly malignant neoplasm. We herein report a case of a 30-year-old woman with an extensive right pulmonary artery tumor who underwent an emergent operation. The tumor was aggressively resected with right pneumonectomy and reconstruction of the right ventricle outflow tract and left pulmonary artery. Although the resected margin at the left pulmonary artery was positive, as confirmed by Mouse double minute type 2 homolog staining, she is doing well and remains free of relapse at 16 months after the operation. Copyright © 2018. Published by Elsevier Inc.

CT Findings of Ruptured Intramural Hematoma of the Aorta Extending Along the Pulmonary Artery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sueyoshi, Eijun, E-mail: EijunSueyoshi@aol.com; Sakamoto, Ichiro; Uetani, Masataka

Mediastinal hematoma extending along the pulmonary artery is a rare complication of Stanford type A classic (double-barreled) aortic dissection. Rupture from the posterior aspect of the aortic root penetrates the shared adventitia of the aorta and pulmonary artery. From this location, hematoma can spread along the adventitial planes of the pulmonary arteries out into the lungs. We report a case of ruptured intramural hematoma of the aorta (IMH) extending along the pulmonary artery. To our knowledge, this finding in patients with IMH has not been reported in the literature.

beta(2)-adrenoceptor antagonist ICI 118,551 decreases pulmonary vascular tone in mice via a G(i/o) protein/nitric oxide-coupled pathway.

PubMed

Wenzel, Daniela; Knies, Ralf; Matthey, Michaela; Klein, Alexandra M; Welschoff, Julia; Stolle, Vanessa; Sasse, Philipp; Röll, Wilhelm; Breuer, Johannes; Fleischmann, Bernd K

2009-07-01

beta(2)-adrenoceptors are important modulators of vascular tone, particularly in the pulmonary circulation. Because neurohormonal activation occurs in pulmonary arterial hypertension, we have investigated the effect of different adrenergic vasoactive substances on tone regulation in large and small pulmonary arteries, as well as in systemic vessels of mice. We found that the beta(2)-adrenoceptor antagonist ICI 118,551 (ICI) evoked a decrease of vascular tone in large pulmonary arteries and reduced the sensitivity of pulmonary arteries toward different contracting agents, eg, norepinephrine, serotonin, or endothelin. ICI proved to act specifically on pulmonary vessels, because it shifted the dose-response curve of norepinephrine to the right in pulmonary arteries, whereas there was no effect in the aorta. Pharmacological experiments proved that the right shift of the norepinephrine dose-response curve by ICI was mediated via a beta(2)-adrenoceptor/G(i/o) protein-dependent pathway enhancing NO production in the endothelium; these results were corroborated in beta-adrenoceptor and endothelial NO synthase knockout mice where ICI had no effect. ICI increased vascular lumen diameter in lung sections and reduced pulmonary arterial pressure under normoxia and under hypoxia in the isolated perfused lung model. These effects were found to be physiologically relevant, because ICI specifically decreased pulmonary but not systemic blood pressure in vivo. Thus, the beta(2)-adrenoceptor antagonist ICI is a pulmonary arterial-specific vasorelaxant and, therefore, a potentially interesting novel therapeutic agent for the treatment of pulmonary arterial hypertension.

NMDA-Type Glutamate Receptor Activation Promotes Vascular Remodeling and Pulmonary Arterial Hypertension.

PubMed

Dumas, Sébastien J; Bru-Mercier, Gilles; Courboulin, Audrey; Quatredeniers, Marceau; Rücker-Martin, Catherine; Antigny, Fabrice; Nakhleh, Morad K; Ranchoux, Benoit; Gouadon, Elodie; Vinhas, Maria-Candida; Vocelle, Matthieu; Raymond, Nicolas; Dorfmüller, Peter; Fadel, Elie; Perros, Frédéric; Humbert, Marc; Cohen-Kaminsky, Sylvia

2018-05-29

Excessive proliferation and apoptosis resistance in pulmonary vascular cells underlie vascular remodeling in pulmonary arterial hypertension (PAH). Specific treatments for PAH exist, mostly targeting endothelial dysfunction, but high pulmonary arterial pressure still causes heart failure and death. Pulmonary vascular remodeling may be driven by metabolic reprogramming of vascular cells to increase glutaminolysis and glutamate production. The N -methyl-d-aspartate receptor (NMDAR), a major neuronal glutamate receptor, is also expressed on vascular cells, but its role in PAH is unknown. We assessed the status of the glutamate-NMDAR axis in the pulmonary arteries of patients with PAH and controls through mass spectrometry imaging, Western blotting, and immunohistochemistry. We measured the glutamate release from cultured pulmonary vascular cells using enzymatic assays and analyzed NMDAR regulation/phosphorylation through Western blot experiments. The effect of NMDAR blockade on human pulmonary arterial smooth muscle cell proliferation was determined using a BrdU incorporation assay. We assessed the role of NMDARs in vascular remodeling associated to pulmonary hypertension, in both smooth muscle-specific NMDAR knockout mice exposed to chronic hypoxia and the monocrotaline rat model of pulmonary hypertension using NMDAR blockers. We report glutamate accumulation, upregulation of the NMDAR, and NMDAR engagement reflected by increases in GluN1-subunit phosphorylation in the pulmonary arteries of human patients with PAH. K v channel inhibition and type A-selective endothelin receptor activation amplified calcium-dependent glutamate release from human pulmonary arterial smooth muscle cell, and type A-selective endothelin receptor and platelet-derived growth factor receptor activation led to NMDAR engagement, highlighting crosstalk between the glutamate-NMDAR axis and major PAH-associated pathways. The platelet-derived growth factor-BB-induced proliferation of human pulmonary arterial smooth muscle cells involved NMDAR activation and phosphorylated GluN1 subunit localization to cell-cell contacts, consistent with glutamatergic communication between proliferating human pulmonary arterial smooth muscle cells via NMDARs. Smooth-muscle NMDAR deficiency in mice attenuated the vascular remodeling triggered by chronic hypoxia, highlighting the role of vascular NMDARs in pulmonary hypertension. Pharmacological NMDAR blockade in the monocrotaline rat model of pulmonary hypertension had beneficial effects on cardiac and vascular remodeling, decreasing endothelial dysfunction, cell proliferation, and apoptosis resistance while disrupting the glutamate-NMDAR pathway in pulmonary arteries. These results reveal a dysregulation of the glutamate-NMDAR axis in the pulmonary arteries of patients with PAH and identify vascular NMDARs as targets for antiremodeling treatments in PAH. © 2018 American Heart Association, Inc.

Angioscopy Is Useful In The Evaluation Of Chronic Pulmonary Arterial Obstruction

NASA Astrophysics Data System (ADS)

Shure, Deborah; Gregoratos, Gabriel; Moser, Kenneth M.

1984-10-01

We have previously described a fiberoptic angioscope for diagnostic use in the right heart and pulmonary arteries. The instrument has a 4 mm 0.D., a proximal flexion control lever, and a 0.8 mm inner channel used to inflate a polyurethane balloon attached to the distal end of the instrument. A conventional xenon light source provides illumination. The instrument is inserted through a right jugular venotomy and passed into the right heart and pulmonary arteries using direct vision and fluoroscopic guidance. The procedure has been performed in 4 patients with pulmonary hypertension suspected to be caused by chronic pulmonary emboli. Chronic emboli were found in two patients and central (resectable) emboli could be distinguished from peripheral ones. The third patient had normal pulmonary arterial intima and a final diagnosis of primary pulmonary hypertension was made. The fourth patient had extrinsic compression of pulmonary arteries by enlarged mediastinal nodes secondary to fibrosing mediastinitis. No complications occurred. We conclude that angioscopy appears to be useful in the diagnostic evaluation of patients with suspected chronic obstruction of the pulmonary arteries.

Takotsubo cardiomyopathy after treatment of pulmonary arterial hypertension

PubMed Central

Cork, David P.; Mehrotra, Amit K.; Gomberg-Maitland, Mardi

2012-01-01

Pulmonary arterial hypertension is a fatal disease. Intravenous prostanoids are often utilized for long-term management of patients. The therapy requires a significant commitment and change in lifestyle for both the patient and family. Takotsubo cardiomyopathy, transient apical ballooning syndrome, has been reported in association with emotional and physical stress. This case report describes a patient with pulmonary arterial hypertension who developed Takotsubo cardiomyopathy after treatment initiation with intravenous treprostinil. Over time, the syndrome resolved and the patient had return of normal left ventricular function. Takotsubo cardiomyopathy should be recognized as a potential, rare complication of therapy initiation due to the severity of the illness and the emotional stress of the disease. PMID:23130109

Estimating core temperature in infants and children after cardiac surgery: a comparison of six methods.

PubMed

Maxton, Fiona J C; Justin, Linda; Gillies, Donna

2004-01-01

Monitoring temperature in critically ill children is an important component of care, yet the accuracy of methods is often questioned. Temperature measured in the pulmonary artery is considered the 'gold standard', but this route is unsuitable for the majority of patients. An accurate, reliable and less invasive method is, however, yet to be established in paediatric intensive care work. To determine which site most closely reflects core temperature in babies and children following cardiac surgery, by comparing pulmonary artery temperature to the temperature measured at rectal, bladder, nasopharyngeal, axillary and tympanic sites. A convenience sample of 19 postoperative cardiac patients was studied. Temperature was recorded as a continuous measurement from pulmonary artery, rectal, nasopharyngeal and bladder sites. Axillary and tympanic temperatures were recorded at 30 minute intervals for 6 1/2 hours postoperatively. The small sample size of 19 infants and children limits the generalizability of the study. Repeated measures analysis of variance demonstrated no significant difference between pulmonary artery and bladder temperatures, and pulmonary artery and nasopharyngeal temperatures. Intraclass correlation showed that agreement was greatest between pulmonary artery temperature and temperature measured by bladder catheter. There was a significant difference between pulmonary artery temperature and temperature measured at rectal, tympanic and pulmonary artery and axillary sites. Repeated measures analysis showed a significant lag between pulmonary artery and rectal temperature of between 0 and 150 minutes after the 6-hour measurement period. In this study, bladder temperature was shown to be the best estimate of pulmonary artery temperature, closely followed by the temperature measured by nasopharyngeal probe. The results support the use of bladder or nasopharyngeal catheters to monitor temperature in critically ill children after cardiac surgery.

Flow-related Right Ventricular - Pulmonary Arterial Pressure Gradients during Exercise.

PubMed

Wright, Stephen P; Opotowsky, Alexander R; Buchan, Tayler A; Esfandiari, Sam; Granton, John T; Goodman, Jack M; Mak, Susanna

2018-06-06

The assumption of equivalence between right ventricular and pulmonary arterial systolic pressure is fundamental to several assessments of right ventricular or pulmonary vascular hemodynamic function. Our aims were to 1) determine whether systolic pressure gradients develop across the right ventricular outflow tract in healthy adults during exercise, 2) examine the potential correlates of such gradients, and 3) consider the effect of such gradients on calculated indices of right ventricular function. Healthy untrained and endurance-trained adult volunteers were studied using right-heart catheterization at rest and during submaximal cycle ergometry. Right ventricular and pulmonary artery pressures were simultaneously transduced, and cardiac output was determined by thermodilution. Systolic pressures, peak and mean gradients, and indices of chamber, vascular, and valve function were analyzed offline. Summary data are reported as mean ± standard deviation or median [interquartile range]. No significant right ventricular outflow tract gradients were observed at rest (mean gradient = 4 [3-5] mmHg), and calculated effective orifice area was 3.6±1.0 cm2. Right ventricular systolic pressure increases during exercise were greater than that of pulmonary artery systolic pressure. Accordingly, mean gradients developed during light exercise (8 [7-9] mmHg) and increased during moderate exercise (12 [9-14] mmHg, p < 0.001). The magnitude of the mean gradient was linearly related to cardiac output (r2 = 0.70, p < 0.001). In healthy adults without pulmonic stenosis, systolic pressure gradients develop during exercise, and the magnitude is related to blood flow rate.

Protective effects of drag-reducing polymers in a rat model of monocrotaline-induced pulmonary hypertension.

PubMed

Wang, Yali; Hu, Feng; Mu, Xiaoyan; Wu, Feng; Yang, Dechun; Zheng, Guixiang; Sun, Xiaoning; Gong, Kaizheng; Zhang, Zhengang

2016-01-27

Drag-reducing polymers (DRPs) are blood-soluble macromolecules which may increase blood flow and reduce vascular resistance. The purpose of the present study was to observe the effect of DRPs on monocrotaline-induced pulmonary hypertension (PH) in the rat model. A total of 64 male Wistar rats were randomly divided into four groups: Group I (pulmonary hypertension model + DRP treatment); Group II (pulmonary hypertension model + saline treatment); Group III (control + DRP treatment); Group IV (control + saline treatment). After five weeks, comparisons were made of the following indices: survival rate, body weight, blood pressure, right ventricular systolic pressure, right ventricular hypertrophy, wall thickness of pulmonary arteries, the internal diameter of small pulmonary arteries, plasma IL-1β and IL-6. The survival rate after 5 weeks varied significantly across all groups (P=0.013), but the survival rates of Groups I and II were not statistically significantly different. Administration of DRP (intravenous injection twice weekly) attenuated the PH-induced increase in right ventricular systolic pressure and suppressed the increases in right ventricular (RV) weight and the ratio of right ventricular weight to left ventricle plus septum weight (RV/LV + S). DRP treatment also significantly decreased the wall thickness of pulmonary arteries, augmented the internal diameter of small pulmonary arteries, and suppressed increases in the plasma levels of IL-1β and IL-6. DRP treatment with intravenous injection effectively inhibited the development of monocrotaline-induced pulmonary hypertension in the rat model. DRPs may have potential application for the treatment of pulmonary hypertension.

Pulmonary Arterial Hypertension

MedlinePlus

Pulmonary Arterial Hypertension What Is Pulmonary Hypertension? To understand pulmonary hypertension (PH) it helps to understand how blood ows throughout your body. While the heart is one organ, it ...

Roles of preoperative arterial blood gas tests in the surgical treatment of scoliosis with moderate or severe pulmonary dysfunction.

PubMed

Liu, Jia-Ming; Shen, Jian-Xiong; Zhang, Jian-Guo; Zhao, Hong; Li, Shu-Gang; Zhao, Yu; Qiu, Giu-Xing

2012-01-01

It has been stated that preoperative pulmonary function tests are essential to assess the surgical risk in patients with scoliosis. Arterial blood gas tests have also been used to evaluate pulmonary function before scoliotic surgery. However, few studies have been reported. The aim of this study was to investigate the roles of preoperative arterial blood gas tests in the surgical treatment of scoliosis with moderate or severe pulmonary dysfunction. This study involved scoliotic patients with moderate or severe pulmonary dysfunction (forced vital capacity < 60%) who underwent surgical treatment between January 2002 and April 2010. A total of 73 scoliotic patients (23 males and 50 females) with moderate or severe pulmonary dysfunction were included. The average age of the patients was 16.53 years (ranged 10 - 44). The demographic distribution, medical records, and radiographs of all patients were collected. All patients received arterial blood gas tests and pulmonary function tests before surgery. The arterial blood gas tests included five parameters: partial pressure of arterial oxygen, partial pressure of arterial carbon dioxide, alveolar-arterial oxygen tension gradient, pH, and standard bases excess. The pulmonary function tests included three parameters: forced expiratory volume in 1 second ratio, forced vital capacity ratio, and peak expiratory flow ratio. All five parameters of the arterial blood gas tests were compared between the two groups with or without postoperative pulmonary complications by variance analysis. Similarly, all three parameters of the pulmonary function tests were compared. The average coronal Cobb angle before surgery was 97.42° (range, 50° - 180°). A total of 15 (20.5%) patients had postoperative pulmonary complications, including hypoxemia in 5 cases (33.3%), increased requirement for postoperative ventilatory support in 4 (26.7%), pneumonia in 2 (13.3%), atelectasis in 2 (13.3%), pneumothorax in 1 (6.7%), and hydrothorax in 1 (6.7%). No significant differences in demographic characteristics or perioperative factors (P > 0.05) existed between the two groups with or without postoperative pulmonary complications. According to the variance analysis, there were no statistically significant differences in any parameter of the arterial blood gas tests between the two groups. No significant correlation between the results of the preoperative arterial blood gas tests and postoperative pulmonary complications existed in scoliotic patients with moderate or severe pulmonary dysfunction. However, the postoperative complications tended to increase with the decrease of partial pressure of arterial oxygen in the arterial blood gas tests.

Pulmonary artery wave propagation and reservoir function in conscious man: impact of pulmonary vascular disease, respiration and dynamic stress tests.

PubMed

Su, Junjing; Manisty, Charlotte; Simonsen, Ulf; Howard, Luke S; Parker, Kim H; Hughes, Alun D

2017-10-15

Wave travel plays an important role in cardiovascular physiology. However, many aspects of pulmonary arterial wave behaviour remain unclear. Wave intensity and reservoir-excess pressure analyses were applied in the pulmonary artery in subjects with and without pulmonary hypertension during spontaneous respiration and dynamic stress tests. Arterial wave energy decreased during expiration and Valsalva manoeuvre due to decreased ventricular preload. Wave energy also decreased during handgrip exercise due to increased heart rate. In pulmonary hypertension patients, the asymptotic pressure at which the microvascular flow ceases, the reservoir pressure related to arterial compliance and the excess pressure caused by waves increased. The reservoir and excess pressures decreased during Valsalva manoeuvre but remained unchanged during handgrip exercise. This study provides insights into the influence of pulmonary vascular disease, spontaneous respiration and dynamic stress tests on pulmonary artery wave propagation and reservoir function. Detailed haemodynamic analysis may provide novel insights into the pulmonary circulation. Therefore, wave intensity and reservoir-excess pressure analyses were applied in the pulmonary artery to characterize changes in wave propagation and reservoir function during spontaneous respiration and dynamic stress tests. Right heart catheterization was performed using a pressure and Doppler flow sensor tipped guidewire to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery in control subjects and patients with pulmonary arterial hypertension (PAH) at rest. In controls, recordings were also obtained during Valsalva manoeuvre and handgrip exercise. The asymptotic pressure at which the flow through the microcirculation ceases, the reservoir pressure related to arterial compliance and the excess pressure caused by arterial waves increased in PAH patients compared to controls. The systolic and diastolic rate constants also increased, while the diastolic time constant decreased. The forward compression wave energy decreased by ∼8% in controls and ∼6% in PAH patients during expiration compared to inspiration, while the wave speed remained unchanged throughout the respiratory cycle. Wave energy decreased during Valsalva manoeuvre (by ∼45%) and handgrip exercise (by ∼27%) with unaffected wave speed. Moreover, the reservoir and excess pressures decreased during Valsalva manoeuvre but remained unaltered during handgrip exercise. In conclusion, reservoir-excess pressure analysis applied to the pulmonary artery revealed distinctive differences between controls and PAH patients. Variations in the ventricular preload and afterload influence pulmonary arterial wave propagation as demonstrated by changes in wave energy during spontaneous respiration and dynamic stress tests. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Oral therapies for pulmonary arterial hypertension: endothelin receptor antagonists and phosphodiesterase-5 inhibitors.

PubMed

Channick, Richard; Preston, Iona; Klinger, James R

2013-12-01

The development of orally active pulmonary vasodilators has been a major breakthrough in the treatment of pulmonary arterial hypertension (PAH). Orally active medications greatly enhanced patient access to PAH treatment and increased an interest in the diagnosis and treatment of this disease that still continues. Four different orally active drugs are currently available for the treatment of PAH and several more are undergoing evaluation. This article discusses the mechanisms by which endothelin receptor antagonists and phosphodiesterase-5 inhibitors mitigate pulmonary hypertensive responses, and reviews the most recent data concerning their efficacy and limitations in the treatment of PAH. Copyright © 2013 Elsevier Inc. All rights reserved.

Isolated supravalvular pulmonary stenosis in a 25-day-old newborn infant: an occasional and early diagnosis.

PubMed

Patanè, Salvatore; Marte, Filippo; Di Bella, Gianluca; Di Tommaso, Eleonora; Pagano, Giuseppina Tindara; Coglitore, Sebastiano

2009-04-03

Pulmonary stenosis comprises variable pathologic features from the right ventricular outflow tract to the peripheral pulmonary arteries. Most frequently, the obstruction occurs at the level of the pulmonary valve; however, it occurs less frequently at the infindibular level. It can occur as part of more congenital cardiac malformations such as tetralogy of Fallot, complete transposition of great arteries, or atrial septal defect. Proximal pulmonary artery stenosis has also been reported as an acquired lesion in infants treated for congenital heart disease. Primary isolated supravalvular pulmonary stenosis is less common. We present a case of primary isolated pulmonary artery stenosis in an asymptomatic 25-day-old newborn infant.

Effects of terlipressin on systolic pulmonary artery pressure of patients with liver cirrhosis: An echocardiographic assessment

PubMed Central

Altintas, Engin; Akkus, Necdet; Gen, Ramazan; Helvaci, M. Rami; Sezgin, Orhan; Oguz, Dilek

2004-01-01

AIM: Portopulmonary hypertension is a serious complication of chronic liver disease. Our aim was to search into the effect of terlipressin on systolic pulmonary artery pressure among cirrhotic patients. METHODS: Twelve patients (6 males and 6 females) with liver cirrhosis were recruited in the study. Arterial blood gas samples were obtained in sitting position at rest. Contrast enhanced echocardiography and measurements of systolic pulmonary artery pressure were performed before and after the intravenous injection of 2 mg terlipressin. RESULTS: Of 12 patients studied, the contrast enhanced echocardiography was positive in 5, and the positive findings in contrast enhanced echocardiography were reversed to normal in two after terlipressin injection. The mean systolic pulmonary artery pressure was 25.5 ± 3.6 mmHg before terlipressin injection, and was 22.5 ± 2.5 mmHg after terlipressin (P = 0.003). The systolic pulmonary artery pressure was above 25 mmHg in seven of these 12 patients. After the terlipressin injection, systolic pulmonary artery pressure was < 25 mmHg in four of these cases (58.3% vs 25%, P = 0.04). CONCLUSION: Terlipressin can decrease the systolic pulmonary artery pressure in patients with liver cirrhosis. PMID:15259082

A Case of Pulmonary Hypertension Due to Fistulas Between Multiple Systemic Arteries and the Right Pulmonary Artery in an Adult Discovered for Occulted Dyspnoea.

PubMed

Li, Ji-Feng; Zhai, Zhen-Guo; Kuang, Tu-Guang; Liu, Min; Ma, Zhan-Hong; Li, Yi-Dan; Yang, Yuan-Hua

2017-08-01

Pulmonary hypertension (PH) can be caused by a fistula between the systemic and pulmonary arteries. Here, we report a case of PH due to multiple fistulas between systemic arteries and the right pulmonary artery where the ventilation/perfusion scan showed no perfusion in the right lung. A 32-year-old male patient was hospitalised for community-acquired pneumonia. After treatment with antibiotics, the pneumonia was alleviated but dyspnoea persisted. Pulmonary hypertension was diagnosed using right heart catheterisation, which detected the mean pulmonary artery pressure as 37mmHg. The anomalies were confirmed by contrast-enhanced CT scan (CT pulmonary angiography), systemic arterial angiography and pulmonary angiography. Following embolisation of the largest fistula, the haemodynamics and oxygen dynamics did not improve, and even worsened to some extent. After supportive therapy including diuretics and oxygen, the patient's dyspnoea, WHO function class and right heart function by transthoracic echocardiography all improved during follow-up. Pulmonary hypertension can be present even when the right lung perfusion is lost. Closure of fistulas by embolisation, when those fistulas act as the proliferating vessels, may be harmful. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

DNA Damage and Pulmonary Hypertension

PubMed Central

Ranchoux, Benoît; Meloche, Jolyane; Paulin, Roxane; Boucherat, Olivier; Provencher, Steeve; Bonnet, Sébastien

2016-01-01

Pulmonary hypertension (PH) is defined by a mean pulmonary arterial pressure over 25 mmHg at rest and is diagnosed by right heart catheterization. Among the different groups of PH, pulmonary arterial hypertension (PAH) is characterized by a progressive obstruction of distal pulmonary arteries, related to endothelial cell dysfunction and vascular cell proliferation, which leads to an increased pulmonary vascular resistance, right ventricular hypertrophy, and right heart failure. Although the primary trigger of PAH remains unknown, oxidative stress and inflammation have been shown to play a key role in the development and progression of vascular remodeling. These factors are known to increase DNA damage that might favor the emergence of the proliferative and apoptosis-resistant phenotype observed in PAH vascular cells. High levels of DNA damage were reported to occur in PAH lungs and remodeled arteries as well as in animal models of PH. Moreover, recent studies have demonstrated that impaired DNA-response mechanisms may lead to an increased mutagen sensitivity in PAH patients. Finally, PAH was linked with decreased breast cancer 1 protein (BRCA1) and DNA topoisomerase 2-binding protein 1 (TopBP1) expression, both involved in maintaining genome integrity. This review aims to provide an overview of recent evidence of DNA damage and DNA repair deficiency and their implication in PAH pathogenesis. PMID:27338373

[Comparison of atrio-ventricular and total cavo-pulmonary connections versus atrio-pulmonary anastomosis for repair of tricuspid atresia in dogs].

PubMed

Yu, C; Liu, Y; Zhu, X; Li, Y; Li, Y

2000-03-01

To compare the hemodynamic effect and energy loss of atrio-ventricular and total cavo-pulmonary connections versus atrio-pulmonary anastomosis for modified Fontan in dogs. Fifteen adult mongrel dogs were divided into three groups. Group I underwent right atrium to right ventricle (using 50% and 25% right ventricular chamber, respectively) connection with the flap of valved homo-pulmonary artery (modified Bjoerk procedure). Group II underwent total cavo-pulmonary connection. Group III received atrio-pulmonary anastomosis. Right atrium pressure, pulmonary artery pressure, and cardiac output were measured by Swan-Ganz catheter. The volumes of the right pulmonary artery, left pulmonary artery, superior vena cava and inferior vena cava were measured by electromagnetic flowmeter. The flow-rate of the right pulmonary artery, left pulmonary artery, superior vena cava and inferior vena cava were measured echocardiographically. The fluid energy loss was calculated. The postoperative right atrium pressure in group I was lower than in group III (P < 0.05). The postoperative stroke index in group I and group II was higher than in group III (P < 0.01). The fluid energy loss was decreased when 50% or 25% right ventricle chamber was used (P < 0.01) and the fluid energy less in group II was less than in group III. Our experience suggested that atrio-ventricular connection and total cavo-pulmonary connection would be better than atrio-pulmonary anastomosis for modified Fontan repair of tricuspid valve atresia.

Pulmonary hemodynamics and gas exchange in off pump coronary artery bypass grafting.

PubMed

Vedin, Jenny; Jensen, Ulf; Ericsson, Anders; Samuelsson, Sten; Vaage, Jarle

2005-10-01

To investigate the influence of cardiopulmonary bypass on pulmonary hemodynamics and gas exchange. Low risk patients admitted for elective coronary artery bypass grafting were randomized to either on (n=25) or off pump (n=25) surgery. Central hemodynamics, gas exchange, and venous admixture were studied during and up to 20 h after surgery. There was no difference in pulmonary vascular resistance index (P=0.16), right ventricular stroke work index (P>0.2), mean pulmonary artery pressure (P>0.2) or pulmonary capillary wedge pressure (P>0.2) between groups. Soon after surgery there was a tendency towards higher cardiac index (P=0.07) in the off pump group. Arterial oxygen tension (P>0.2), hematocrit (P>0.2), venous admixture (P>0.2), and arterial-venous oxygen content difference (P=0.12) did not differ between groups. This prospective, randomized study showed no difference in pulmonary hemodynamics, pulmonary gas exchange, and venous admixture, in low risk patients undergoing off pump compared to on pump coronary artery bypass surgery.

Dasatinib-induced pulmonary arterial hypertension - A rare late complication.

PubMed

Ibrahim, Uroosa; Saqib, Amina; Dhar, Vidhya; Odaimi, Marcel

2018-01-01

Dasatinib is a dual Src/Abl tyrosine kinase inhibitor approved for frontline and second line treatment of chronic phase chronic myelogenous leukemia. Pulmonary arterial hypertension is defined by an increase in mean pulmonary arterial pressure >25 mmHg at rest. Dasatinib-induced pulmonary hypertension has been reported in less than 1% of patients on chronic dasatinib treatment for chronic myelogenous leukemia. The pulmonary arterial hypertension from dasatinib may be categorized as either group 1 (drug-induced) or group 5 based on various mechanisms that may be involved including the pathogenesis of the disease process of chronic myelogenous leukemia. There have been reports of dasatinib-induced pulmonary arterial hypertension being reversible. We report a case of pulmonary arterial hypertension in a 46-year-old female patient with chronic phase chronic myelogenous leukemia on dasatinib treatment for over 10 years. She had significant improvement in symptoms after discontinuation of dasatinib and initiation of vasodilators. Several clinical questions arise once patients experience significant adverse effects as discussed in our case.

Automatic multiscale enhancement and segmentation of pulmonary vessels in CT pulmonary angiography images for CAD applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou Chuan; Chan, H.-P.; Sahiner, Berkman

2007-12-15

The authors are developing a computerized pulmonary vessel segmentation method for a computer-aided pulmonary embolism (PE) detection system on computed tomographic pulmonary angiography (CTPA) images. Because PE only occurs inside pulmonary arteries, an automatic and accurate segmentation of the pulmonary vessels in 3D CTPA images is an essential step for the PE CAD system. To segment the pulmonary vessels within the lung, the lung regions are first extracted using expectation-maximization (EM) analysis and morphological operations. The authors developed a 3D multiscale filtering technique to enhance the pulmonary vascular structures based on the analysis of eigenvalues of the Hessian matrix atmore » multiple scales. A new response function of the filter was designed to enhance all vascular structures including the vessel bifurcations and suppress nonvessel structures such as the lymphoid tissues surrounding the vessels. An EM estimation is then used to segment the vascular structures by extracting the high response voxels at each scale. The vessel tree is finally reconstructed by integrating the segmented vessels at all scales based on a 'connected component' analysis. Two CTPA cases containing PEs were used to evaluate the performance of the system. One of these two cases also contained pleural effusion disease. Two experienced thoracic radiologists provided the gold standard of pulmonary vessels including both arteries and veins by manually tracking the arterial tree and marking the center of the vessels using a computer graphical user interface. The accuracy of vessel tree segmentation was evaluated by the percentage of the 'gold standard' vessel center points overlapping with the segmented vessels. The results show that 96.2% (2398/2494) and 96.3% (1910/1984) of the manually marked center points in the arteries overlapped with segmented vessels for the case without and with other lung diseases. For the manually marked center points in all vessels including arteries and veins, the segmentation accuracy are 97.0% (4546/4689) and 93.8% (4439/4732) for the cases without and with other lung diseases, respectively. Because of the lack of ground truth for the vessels, in addition to quantitative evaluation of the vessel segmentation performance, visual inspection was conducted to evaluate the segmentation. The results demonstrate that vessel segmentation using our method can extract the pulmonary vessels accurately and is not degraded by PE occlusion to the vessels in these test cases.« less

3D Printing to Model Surgical Repair of Complex Congenitally Corrected Transposition of the Great Arteries.

PubMed

Sahayaraj, R Anto; Ramanan, Sowmya; Subramanyan, Raghavan; Cherian, Kotturathu Mammen

2017-01-01

We report the use of three-dimensional (3D) modeling to plan surgery for physiologic repair of congenitally corrected transposition of the great arteries with pulmonary atresia, dextrocardia, and complex intra cardiac anatomy. Based on measurements made from the 3D printed model of the actual patient's anatomy, we anticipated using a composite valved conduit (Dacron tube graft, decellularized bovine jugular vein, and aortic homograft) to establish left ventricle-to-pulmonary artery continuity with relief of stenosis involving the pulmonary artery confluence and bilateral branch pulmonary arteries.

The β2 agonist terbutaline specifically decreases pulmonary arterial pressure under normoxia and hypoxia via α adrenoceptor antagonism.

PubMed

Neumann, Vanessa; Knies, Ralf; Seidinger, Alexander; Simon, Annika; Lorenz, Kristina; Matthey, Michaela; Breuer, Johannes; Wenzel, Daniela

2018-05-01

Pulmonary hypertension is a severe, incurable disease with a poor prognosis. Although treatment regimens have improved during the last 2 decades, current pharmacologic strategies are limited and focus on the modulation of only a few pathways related to endothelin, NO, and prostacyclin signaling. Therefore, the identification of novel molecular targets is urgently needed. We found that the β 2 adrenoceptor (AR) agonists terbutaline (TER) and salbutamol induced a dose-dependent vasorelaxation in large pulmonary arteries but not aortas of mouse. This effect was found to be independent of β ARs and the endothelium but was determined by the type of the preconstrictor. Vasodilation by β 2 AR agonists occurred after pretreatment of pulmonary arteries with phenylephrine and serotonin, both agonists of α 1 ARs, but was absent after preconstriction with the thromboxane analog U46619. These data indicated α-adrenolytic activity of β 2 AR agonists, which was confirmed by a right shift of the phenylephrine dose-response curve by TER. This effect was physiologically relevant because TER also relaxed small intrapulmonary arteries in lung slices and diminished pulmonary arterial pressure in an isolated perfused lung model under normoxia and hypoxia. Finally, TER applied as an aerosol also selectively decreased pulmonary arterial pressure without effects on systemic blood pressure and heart rate in mouse in vivo. Thus, β 2 AR agonists display α-adrenolytic activity in pulmonary arteries ex vivo and in vivo, and may provide a novel option to reduce pulmonary arterial pressure in pulmonary hypertension.-Neumann, V., Knies, R., Seidinger, A., Simon, A., Lorenz, K., Matthey, M., Breuer, J., Wenzel, D. The β 2 agonist terbutaline specifically decreases pulmonary arterial pressure under normoxia and hypoxia via α adrenoceptor antagonism.

[The effect of calcitonin gene-related peptide on collagen accumulation in pulmonary arteries of rats with hypoxic pulmonary arterial hypertension].

PubMed

Li, Xian-Wei; Du, Jie; Li, Yuan-Jian

2013-03-01

To observe the effect of calcitonin gene-related peptide (CGRP) on pulmonary vascular collagen accumulation in hypoxia rats in order to study the effect of CGRP on hypoxic pulmonary vascular structural remodeling and its possible mechanism. Rats were acclimated for 1 week, and then were randomly divided into three groups: normoxia group, hypoxia group, and hypoxia plus capsaicin group. Pulmonary arterial hypertension was induced by hypoxia in rats. Hypoxia plus capsaicin group, rats were given capsaicin (50 mg/(kg x d), s.c) 4 days before hypoxia to deplete endogenous CGRP. Hypoxia (3% O2) stimulated proliferation of pulmonary arterial smooth muscle cells (PASMCs) and proliferation was measured by BrdU marking. The expression levels of CGRP, phosphorylated ERK1/2 (p-ERK1/ 2), collagen I and collagen III were detected by real-time PCR or Western blot. Right ventricle systolic pressure (RVSP) and mean pulmonary arterial pressure (mPAP) of pulmonary arterial hypertension (PAH) rats induced by hypoxia were higher than those of normoxia rats. By HE and Masson staining, it was demonstrated that hypoxia also significantly induced hypertrophy of pulmonary arteries and increased level of collagen accumulation. Hypoxia dramatically decreased the CGRP level and increased the expression of p-ERK1/2, collagen I, collagen III in pulmonary arteries. All these effects of hypoxia were further aggravated by pre-treatment of rats with capsaicin. CGRP concentration-dependently inhibited hypoxia-induced proliferation of PASMCs, markedly decreased the expression of p-ERK1/2, collagen I and collagen III. All these effects of CGRP were abolished in the presence of CGRP8-37. These results suggest that CGRP might inhibit hypoxia-induced PAH and pulmonary vascular remodeling, through inhibiting phosphorylation of ERK1/2 and alleviating the collagen accumulation of pulmonary arteries.

Assessment of branch pulmonary artery stenosis in children after repair of tetralogy of Fallot using lung perfusion scintigraphy comparison with echocardiography.

PubMed

Chien, Kuang-Jen; Huang, Hurng-Wern; Huang, Ta-Cheng; Lee, Cheng-Liang; Weng, Ken-Pen; Lin, Chu-Chuan; Shieh, Po-Chuen; Wu, Ming-Ting; Hsieh, Kai-Sheng

2016-01-01

The aim of this study was to compare the usefulness of lung perfusion scintigraphy and echocardiogram in the evaluation of the branch pulmonary arteries stenosis in children with tetralogy of Fallot (TOF). From February 2006 to November 2008, 74 children (mean age 7.8 years, range 1–18 years) who underwent repair of TOF at ages from 10 months to 13 years were suspected to have unilateral or bilateral branch pulmonary artery stenosis. In all patients, cardiac angiography was performed to confirm the diagnosis of branch pulmonary artery stenosis. Lung perfusion scintigraphy and two-dimensional transthoracic echocardiography were performed in all patients to compare their abilities to diagnose branch pulmonary artery stenosis. Of the 74 patients, 51 cases were found to have branch pulmonary artery stenosis by cardiac angiography. There was agreement between the scintigraphic and angiographic findings in 44 (86%) patients and there were discrepancies in 11 (15%) patients. The positive predictive value of our lung perfusion scintigraphy in detecting the branch pulmonary artery stenosis was 92 %. The positive and negative likelihood ratios of lung perfusion scintigraphy were 4.96 and 0.17, respectively. There was conformity between the echocardiographic and angiographic findings in 40 (78%) patients with discrepancies in 16 (21%) patients. The positive predictive value of our echocardiography in detecting the branch pulmonary artery stenosis was 89%. The positive and negative likelihood ratios of echocardiography were 3.61 and 0.28, respectively. Lung perfusion scintigraphy is a valuable, non-invasive screening tool in the assessment of branch pulmonary artery stenosis in children after TOF.

Decline in arterial partial pressure of oxygen after exercise: a surrogate marker of pulmonary vascular obstructive disease in patients with atrial septal defect and severe pulmonary hypertension.

PubMed

Laksmivenkateshiah, Srinivas; Singhi, Anil K; Vaidyanathan, Balu; Francis, Edwin; Karimassery, Sundaram R; Kumar, Raman K

2011-06-01

To examine the utility of decline in arterial partial pressure of oxygen after exercise as a marker of pulmonary vascular obstructive disease in patients with atrial septal defect and pulmonary hypertension. Treadmill exercise was performed in 18 patients with atrial septal defect and pulmonary hypertension. Arterial blood gas samples were obtained before and after peak exercise. A decline in the arterial pressure of oxygen of more than 10 millimetres of mercury after exercise was considered significant based on preliminary tests conducted on the controls. Cardiac catheterisation was performed in all patients and haemodynamic data sets were obtained on room air, oxygen, and a mixture of oxygen and nitric oxide (30-40 parts per million). There were 10 patients who had more than a 10 millimetres of mercury drop in arterial partial pressure of oxygen after exercise and who had a basal pulmonary vascular resistance index of more than 7 Wood units per square metre. Out of eight patients who had less than a 10 millimetres of mercury drop in arterial partial pressure of oxygen after exercise, seven had a basal pulmonary vascular resistance index of less than 7 Wood units per square metre, p equals 0.0001. A decline in arterial partial pressure of oxygen of more than 10 millimetres of mercury predicted a basal pulmonary vascular resistance index of more than 7 Wood units per square metre with a specificity of 100% and a sensitivity of 90%. A decline in arterial partial pressure of oxygen following exercise appears to predict a high pulmonary vascular resistance index in patients with atrial septal defect and pulmonary hypertension. This test is a useful non-invasive marker of pulmonary vascular obstructive disease in this subset.

Non-valvular main pulmonary artery vegetation associated with aortopulmonary window.

PubMed

Unal, M; Tuncer, C; Serçe, K; Bostan, M; Gökçe, M; Erem, C

1995-01-01

We present a 32-year-old female with aortopulmonary window and vegetation of non-valvular main pulmonary artery. The aortopulmonary window is a rare congenital disease in which the aorta and pulmonary arteries are communicated by a defect of variable diameter. The pulmonic valve is the least commonly involved valve in bacterial endocarditis, but there is no vegetation of non-valvular main pulmonary artery in the literature. Colour duplex sonography showed an aortopulmonary window with aortic regurgitation. Magnetic resonance (MR) imaging demonstrating the vegetation on the wall of main pulmonary artery, is an useful and complementary method, and can be used for demonstration of congenital and acquired cardiovascular pathologies including aortopulmonary window and subpulmonic or suprapulmonic vegetations.

Drug-Coated Balloon Angioplasty: A Novel Treatment for Pulmonary Artery In-Stent Stenosis in a Patient with Williams Syndrome.

PubMed

Cohen, Jennifer L; Glickstein, Julie S; Crystal, Matthew A

2017-12-01

A 20-month-old boy with Williams syndrome had undergone multiple surgical and catheter-based interventions for resistant peripheral pulmonary arterial stenoses with eventual bilateral stent placement and conventional balloon angioplasty. He persistently developed suprasystemic right ventricular (RV) pressure. Angioplasty with a drug-coated balloon (DCB) was performed for in-stent restenosis and to remodel his distal pulmonary vessels bilaterally. This resulted in immediate improvement in the in-stent stenosis and resultant decrease in RV pressure. Follow-up catheterization two months later continued to show long-lasting improvement in the in-stent stenosis. We hypothesize that the anti-proliferative effects of DCBs may be of benefit in the arteriopathy associated with Williams syndrome. We report this as a novel use of a DCB in the pulmonary arterial circulation in a patient with Williams syndrome.

Long term cardiovascular consequences of chronic lung disease of prematurity.

PubMed

Poon, Chuen Yeow; Edwards, Martin Oliver; Kotecha, Sailesh

2013-12-01

Pulmonary arterial (PA) hypertension in preterm infant is an important consequence of chronic lung disease of prematurity (CLD) arising mainly due to impaired alveolar development and dysregulated angiogenesis of the pulmonary circulation. Although PA pressure and resistance in these children normalise by school age, their pulmonary vasculature remains hyper-reactive to hypoxia until early childhood. Furthermore, there is evidence that systemic blood pressure in preterm born children with or without CLD is mildly increased at school age and in young adulthood when compared to term-born children. Arterial stiffness may be increased in CLD survivors due to increased smooth muscle tone of the pre-resistance and resistance vessels rather than the loss of elasticity in the large arteries. This review explores the long term effects of CLD on the pulmonary and systemic circulations along with their clinical correlates and therapeutic approaches. Copyright © 2012 Elsevier Ltd. All rights reserved.

Analysis of Tumor Vessel Supply in Lewis Lung Carcinoma in Mice by Fluorescent Microsphere Distribution and Imaging with Micro- and Flat-Panel Computed Tomography

PubMed Central

Savai, Rajkumar; Wolf, Joachim C.; Greschus, Susanne; Eul, Bastian G.; Schermuly, Ralph T.; Hänze, Jörg; Voswinckel, Robert; Langheinrich, Alexander C.; Grimminger, Friedrich; Traupe, Horst; Seeger, Werner; Rose, Frank

2005-01-01

In lung carcinomas the blood supply varies depending on tumor type and stage and can develop from pulmonary or bronchial circulation, or both. To examine this in vivo, primary bronchogenic Lewis lung carcinoma cells were intratracheally instilled in C57BL/6 mice. Within 7 days, histological examinations showed progressive tumor growth at the peripheral parenchymal region. The relative contribution of tumor blood supply via the pulmonary and systemic arteries was studied in detail using fluorescent microspheres (10 μm). When compared to healthy lung parenchyma (13:1), Lewis lung carcinoma tumor tissue (52:1) showed a fourfold increase in pulmonary to systemic microspheres, indicating that the pulmonary arteries are the predominant tumor-feeding vessels. After filling the vessels with a vascular cast, the microanatomy of vessels being derived from the pulmonary artery was visualized with micro computed tomography. Flat-panel volumetric computed tomography provided longitudinal visualization of tissue bridges between the growing tumor and the pulmonary vasculature. In this model of peripheral parenchymal malignancy, new imaging techniques allowed effective visualization of lung tumor growth and vascularization in living mice, demonstrating a pulmonary blood supply for lung tumors. PMID:16192630

VEGF ameliorates pulmonary hypertension through inhibition of endothelial apoptosis in experimental lung fibrosis in rats

PubMed Central

Farkas, Laszlo; Farkas, Daniela; Ask, Kjetil; Möller, Antje; Gauldie, Jack; Margetts, Peter; Inman, Mark; Kolb, Martin

2009-01-01

Idiopathic pulmonary fibrosis (IPF) can lead to the development of secondary pulmonary hypertension (PH) and ultimately death. Despite this known association, the precise mechanism of disease remains unknown. Using a rat model of IPF, we explored the role of the proangiogenic and antiapoptotic growth factor VEGF in the vascular remodeling that underlies PH. In this model, adenoviral delivery of active TGF-β1 induces pulmonary arterial remodeling, loss of the microvasculature in fibrotic areas, and increased pulmonary arterial pressure (PAP). Immunohistochemistry and mRNA analysis revealed decreased levels of VEGF and its receptor, which were inversely correlated with PAP and endothelial cell apoptosis in both the micro- and macrovasculature. Treatment of IPF rats with adenoviral delivery of VEGF resulted in reduced endothelial apoptosis, increased vascularization, and improved PAP due to reduced remodeling but worsened PF. These data show that experimental pulmonary fibrosis (PF) leads to loss of the microvasculature through increased apoptosis and to remodeling of the pulmonary arteries, with both processes resulting in PH. As administration of VEGF ameliorated the PH in this model but concomitantly aggravated the fibrogenic process, VEGF-based therapies should be used with caution. PMID:19381013

PULMONARY ARTERIAL DISEASE ASSOCIATED WITH RIGHT-SIDED CARDIAC HYPERTROPHY AND CONGESTIVE HEART FAILURE IN ZOO MAMMALS HOUSED AT 2,100 M ABOVE SEA LEVEL.

PubMed

Juan-Sallés, Carles; Martínez, Liliana Sofía; Rosas-Rosas, Arely G; Parás, Alberto; Martínez, Osvaldo; Hernández, Alejandra; Garner, Michael M

2015-12-01

Subacute and chronic mountain sickness of humans and the related brisket disease of cattle are characterized by right-sided congestive heart failure in individuals living at high altitudes as a result of sustained hypoxic pulmonary hypertension. Adaptations to high altitude and disease resistance vary among species, breeds, and individuals. The authors conducted a retrospective survey of right-sided cardiac hypertrophy associated with pulmonary arterial hypertrophy or arteriosclerosis in zoo mammals housed at Africam Safari (Puebla, México), which is located at 2,100 m above sea level. Seventeen animals with detailed pathology records matched the study criterion. Included were 10 maras (Dolichotis patagonum), 2 cotton-top tamarins (Saguinus oedipus oedipus), 2 capybaras (Hydrochaeris hydrochaeris), and 1 case each of Bennet's wallaby (Macropus rufogriseus), nilgai antelope (Boselaphus tragocamelus), and scimitar-horned oryx (Oryx dammah). All had right-sided cardiac hypertrophy and a variety of arterial lesions restricted to the pulmonary circulation and causing arterial thickening with narrowing of the arterial lumen. Arterial lesions most often consisted of medial hypertrophy or hyperplasia of small and medium-sized pulmonary arteries. All maras also had single or multiple elevated plaques in the pulmonary arterial trunk consisting of fibrosis, accompanied by chondroid metaplasia in some cases. Both antelopes were juvenile and died with right-sided congestive heart failure associated with severe pulmonary arterial lesions. To the authors' knowledge, this is the first description of cardiac and pulmonary arterial disease in zoo mammals housed at high altitudes.

Impact of Pulmonary Artery Pressure on Exercise Function in Severe COPD

PubMed Central

Sims, Michael W.; Margolis, David J.; Localio, A. Russell; Panettieri, Reynold A.; Kawut, Steven M.; Christie, Jason D.

2009-01-01

Background: Although pulmonary hypertension commonly complicates COPD, the functional consequences of increased pulmonary artery pressures in patients with this condition remain poorly defined. Methods: We conducted a cross-sectional analysis of a cohort of 362 patients with severe COPD who were evaluated for lung transplantation. Patients with pulmonary hemodynamics measured by cardiac catheterization and available 6-min walk test results were included. The association of mean pulmonary artery pressure (mPAP) with pulmonary function, echocardiographic variables, and 6-min walk distance was assessed. Results: The prevalence of pulmonary hypertension (mPAP, > 25 mm Hg; pulmonary artery occlusion pressure [PAOP], < 16 mm Hg) was 23% (95% confidence interval, 19 to 27%). In bivariate analysis, higher mPAP was associated with lower FVC and FEV1, higher Pco2 and lower Po2 in arterial blood, and more right heart dysfunction. Multivariate analysis demonstrated that higher mPAP was associated with shorter distance walked in 6 min, even after adjustment for age, gender, race, height, weight, FEV1, and PAOP (−11 m for every 5 mm Hg rise in mPAP; 95% confidence interval, −21 to −0.7; p = 0.04). Conclusions: Higher pulmonary artery pressures are associated with reduced exercise function in patients with severe COPD, even after controlling for demographics, anthropomorphics, severity of airflow obstruction, and PAOP. Whether treatments aimed at lowering pulmonary artery pressures may improve clinical outcomes in COPD, however, remains unknown. PMID:19318664

Abundance of endothelial nitric oxide synthase in newborn intrapulmonary arteries.

PubMed Central

Hislop, A. A.; Springall, D. R.; Buttery, L. D.; Pollock, J. S.; Haworth, S. G.

1995-01-01

A monoclonal antibody to endothelial NOS (eNOS) was used to demonstrate the distribution and density of eNOS in the developing porcine lung. Lung tissue from large white pigs aged from less than 5 minutes to 3 months was immunostained and, using light microscopy, distribution of eNOS was assessed by a semiquantitative scoring system. At all ages eNOS was located on the endothelial cells of pulmonary and bronchial arteries and veins. Immunoreactivity for eNOS was greater in the larger, more proximal pulmonary arteries than at the periphery. In the lung of newborn pigs immunoreactivity for eNOS was present in arteries of all sizes but some showed no positive staining. At 2-3 days of age almost all arteries showed positive immunoreactivity. By 3 months of age the amount of eNOS had decreased and was less than that seen in the newborn. The highest level of eNOS was seen immediately after birth when the pulmonary arteries are dilating. eNOS may therefore play an important part in adaptation to extra-uterine life. Images Figure 3 Figure 1 Figure 2 PMID:7552590

Acute control of pulmonary regurgitation with a balloon "valve". An experimental investigation.

PubMed

Siwek, L G; Applebaum, R E; Jones, M; Clark, R E

1985-09-01

Operations for certain congenital cardiac lesions can produce pulmonary regurgitation. Pulmonary regurgitation contributes to right ventricular dysfunction, which may cause early postoperative morbidity and mortality. To ameliorate the problems of pulmonary regurgitation during the early postoperative period, we evaluated a method for its acute control. Complete pulmonary valvectomy was performed utilizing inflow occlusion in eight sheep. A catheter with a 15 ml spherical balloon was positioned in the pulmonary arterial trunk; its inflation and deflation were regulated by an intra-aortic balloon pump unit. Blood flow from the pulmonary arterial trunk and forward and regurgitant fraction were determined from electromagnetic flow transducer recordings. The regurgitant fraction with uncontrolled pulmonary regurgitation was 38% +/- 3% (forward flow = 42 +/- 5 ml/beat and regurgitant flow = 16 +/- 2 ml/beat). Inflation of the balloon during diastole was timed to completely eliminate pulmonary regurgitation. This balloon control of pulmonary regurgitation increased pulmonary arterial diastolic pressure from 12 +/- 1 to 17 +/- 1 mm Hg (p less than 0.0001) and decreased pulmonary arterial systolic pressure from 31 +/- 3 to 27 +/- 1 mm Hg (p = 0.06). Pulmonary arterial pulse pressure decreased from 19 +/- 3 to 9 +/- 1 mm Hg (p less than 0.003). Elimination of pulmonary regurgitation decreased right ventricular stroke volume (25 +/- 3 versus 42 +/- 5 ml/beat, p less than 0.0002) and resulted in a 46% reduction in right ventricular stroke work (5.0 +/- 0.6 versus 9.4 +/- 1.0 gm-m/beat, p less than 0.001) with no change in net forward pulmonary artery flow. Thus, acute pulmonary regurgitation can be controlled and this control improves overall hemodynamic status and decreases right ventricular work.

High-resolution CT evaluation of bronchial lumen to vertebral body, pulmonary artery to vertebral body and bronchial lumen to pulmonary artery ratios in Dirofilaria immitis-infected cats with and without selamectin administration.

PubMed

Lee-Fowler, Tekla M; Cole, Robert C; Dillon, A Ray; Graham, Shannon; Tillson, D Michael; Barney, Sharron

2017-10-01

Objectives The bronchial lumen to pulmonary artery (BA) ratio is utilized to evaluate pulmonary pathology on CT images. The BA ratio may be unreliable when changes are present in bronchial and pulmonary arteries concurrently. Bronchial lumen to vertebral body (BV) and pulmonary artery to vertebral body (AV) ratios have been established in normal cats and may serve as an alternative. This study aimed to evaluate the BV, AV and BA ratios in cats before and after infection with Dirofilaria immitis, with and without selamectin administration, and to characterize the distribution of disease. Methods Archived CT images were reviewed from three groups of cats: D immitis-infected untreated (n = 6); infected pretreated with selamectin (n = 6); uninfected untreated (n = 5). The BV, AV and BA ratios were calculated for all lung lobes for baseline (D0) and day 240 (D240) postinfection. Ratios and percentage change from baseline were compared between lobes and between groups. Results BV and AV ratios were more consistent in identifying abnormalities when disease was present in bronchial and arteries concurrently than BA ratios. Infected untreated cats had significant changes in both BV and AV ratios and percentage change from baseline. Abnormal BV and AV ratios were noted in the infected selamectin group, although less widely distributed. Conclusions and relevance The BV and AV ratios more accurately identified bronchial and pulmonary artery abnormalities in D immitis-infected cats. Both bronchial and pulmonary artery changes were present in infected cats, decreasing the diagnostic application of the BA ratio. Pulmonary artery changes were more widely distributed than bronchial changes in the lung. Heartworm-infected cats receiving selamectin had bronchial and pulmonary artery changes but to a lesser extent than untreated heartworm-infected cats. The CT-derived BV and AV ratios are a useful measure to evaluate lung disease of cats.

Obesity-related pulmonary arterial hypertension in rats correlates with increased circulating inflammatory cytokines and lipids and with oxidant damage in the arterial wall but not with hypoxia

PubMed Central

Irwin, David C.; Garat, Chrystelle V.; Crossno, Joseph T.; MacLean, Paul S.; Sullivan, Timothy M.; Erickson, Paul F.; Jackman, Matthew R.; Harral, Julie W.; Reusch, Jane E. B.

2014-01-01

Abstract Obesity is causally linked to a number of comorbidities, including cardiovascular disease, diabetes, renal dysfunction, and cancer. Obesity has also been linked to pulmonary disorders, including pulmonary arterial hypertension (PAH). It was long believed that obesity-related PAH was the result of hypoventilation and hypoxia due to the increased mechanical load of excess body fat. However, in recent years it has been proposed that the metabolic and inflammatory disturbances of obesity may also play a role in the development of PAH. To determine whether PAH develops in obese rats in the absence of hypoxia, we assessed pulmonary hemodynamics and pulmonary artery (PA) structure in the diet-resistant/diet-induced obesity (DR/DIO) and Zucker lean/fatty rat models. We found that high-fat feeding (DR/DIO) or overfeeding (Zucker) elicited PA remodeling, neomuscularization of distal arterioles, and elevated PA pressure, accompanied by right ventricular (RV) hypertrophy. PA thickening and distal neomuscularization were also observed in DIO rats on a low-fat diet. No evidence of hypoventilation or chronic hypoxia was detected in either model, nor was there a correlation between blood glucose or insulin levels and PAH. However, circulating inflammatory cytokine levels were increased with high-fat feeding or calorie overload, and hyperlipidemia and oxidant damage in the PA wall correlated with PAH in the DR/DIO model. We conclude that hyperlipidemia and peripheral inflammation correlate with the development of PAH in obese subjects. Obesity-related inflammation may predispose to PAH even in the absence of hypoxia. PMID:25610600

Ventricular-Arterial Coupling and Exercise-Induced Pulmonary Hypertension During Low-Level Exercise in Heart Failure With Preserved or Reduced Ejection Fraction.

PubMed

Obokata, Masaru; Nagata, Yasufumi; Kado, Yuichiro; Kurabayashi, Masahiko; Otsuji, Yutaka; Takeuchi, Masaaki

2017-03-01

Exercise-induced pulmonary hypertension (EIPH) may develop even at low workloads in heart failure (HF) patients. Ventricular-arterial stiffening plays an important role in the pathophysiology of HF with preserved ejection fraction (HFpEF). This study aimed to compare the response of ventricular-arterial coupling and PH during low-level exercise between HFpEF and HF with reduced EF (HFrEF). Echocardiography was performed at rest and during 10 W of bicycle exercise in HFpEF (n = 37) and HFrEF (n = 43). Load-independent contractility (end-systolic elastance [Ees], preload recruitable stroke work [PRSW], and peak power index [PWRI]), arterial afterload (arterial elastance [Ea]), and ventricular-arterial interaction (Ea/Ees) were measured with the use of a noninvasive single-beat technique. EIPH was defined as an estimated pulmonary arterial systolic pressure (PASP) of ≥50 mm Hg at 10 W of exercise. PASP was significantly increased during 10 W of exercise in both HF types, and ~50% of HFpEF patients developed EIPH. Arterial afterload was increased significantly during exercise in both groups. HFrEF and HFpEF patients showed a significant increase in LV contractility assessed by Ees, PRSW, and PWRI during exercise. Although Ea/Ees ratio decreased significantly in HFrEF, reduction in Ea/Ees was attenuated because of blunted Ees increases in patients with HFpEF compared with HFrEF. Even at low-level exercise, ~50% of HFpEF patients developed EIPH. Reduction in Ea/Ees was attenuated owing to less Ees increase in HFpEF compared with HFrEF. Further studies are needed to elucidate the association between ventricular-arterial coupling and EIPH in HFpEF. Copyright © 2016 Elsevier Inc. All rights reserved.

The pulmonary artery catheter: a critical reappraisal.

PubMed

Gidwani, Umesh K; Mohanty, Bibhu; Chatterjee, Kanu

2013-11-01

Balloon floatation pulmonary artery catheters (PACs) have been used for hemodynamic monitoring in cardiac, medical, and surgical intensive care units since the 1970s. With the availability of newer noninvasive diagnostic modalities, particularly echocardiography, the frequency of diagnostic pulmonary artery catheterization has declined. In this review, the evolution of PACs, the results of nonrandomized and randomized studies in various clinical conditions, the uses and abuses of bedside hemodynamic monitoring, and current indications for pulmonary artery catheterization are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

Pulmonary artery relative area change detects mild elevations in pulmonary vascular resistance and predicts adverse outcome in pulmonary hypertension.

PubMed

Swift, Andrew J; Rajaram, Smitha; Condliffe, Robin; Capener, Dave; Hurdman, Judith; Elliot, Charlie; Kiely, David G; Wild, Jim M

2012-10-01

The aim of this study was to evaluate the clinical use of magnetic resonance imaging measurements related to pulmonary artery stiffness in the evaluation of pulmonary hypertension (PH). A total of 134 patients with suspected PH underwent right heart catheterization (RHC) and magnetic resonance imaging on a 1.5-T scanner within 2 days. Phase contrast imaging at the pulmonary artery trunk and cine cardiac views were acquired. Pulmonary artery area change (AC), relative AC (RAC), compliance (AC/pulse pressure from RHC), distensibility (RAC/pulse pressure from RHC), right ventricular functional indices, and right ventricular mass were all derived. Regression curve fitting identified the statistical model of best fit between RHC measurements and pulmonary artery stiffness indices. The diagnostic accuracy and prognostic value of noninvasive AC and RAC were also assessed. The relationship between pulmonary vascular resistance and pulmonary artery RAC was best reflected by an inverse linear model. Patients with mild elevation in pulmonary vascular resistance (<4 Woods units) demonstrated reduced RAC (P = 0.02) and increased right ventricular mass index (P < 0.0001) without significant loss of right ventricular function (P = 0.17). At follow-up of 0 to 40 months, 18 patients with PH had died (16%). Analysis of Kaplan-Meier plots showed that both AC and RAC predicted mortality (log-rank test, P = 0.046 and P = 0.012, respectively). Area change and RAC were also predictors of mortality using univariate Cox proportional hazards regression analysis (P = 0.046 and P = 0.03, respectively). Noninvasive assessment of pulmonary artery RAC is a marker sensitive to early increased vascular resistance in PH and is a predictor of adverse outcome.

VIP Gene Deletion in Mice Causes Cardiomyopathy Associated with Upregulation of Heart Failure Genes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Szema, Anthony M.; Hamidi, Sayyed A.; Smith, S. David

2013-05-20

Vasoactive Intestinal Peptide (VIP), a pulmonary vasodilator and inhibitor of vascular smooth muscle proliferation, is absent in pulmonary arteries of patients with idiopathic pulmonary arterial hypertension (PAH). We previously determined that targeted deletion of the VIP gene in mice leads to PAH with pulmonary vascular remodeling and right ventricular (RV) dilatation. Whether the left ventricle is also affected by VIP gene deletion is unknown. In the current study, we examined if VIP knockout mice (VIP-/-) develop both right (RV) and left ventricular (LV) cardiomyopathy, manifested by LV dilatation and systolic dysfunction, as well as overexpression of genes conducive to heartmore » failure.« less

Deficiency of Akt1, but not Akt2, attenuates the development of pulmonary hypertension

PubMed Central

Tang, Haiyang; Chen, Jiwang; Fraidenburg, Dustin R.; Song, Shanshan; Sysol, Justin R.; Drennan, Abigail R.; Offermanns, Stefan; Ye, Richard D.; Bonini, Marcelo G.; Minshall, Richard D.; Garcia, Joe G. N.; Machado, Roberto F.; Makino, Ayako

2014-01-01

Pulmonary vascular remodeling, mainly attributable to enhanced pulmonary arterial smooth muscle cell proliferation and migration, is a major cause for elevated pulmonary vascular resistance and pulmonary arterial pressure in patients with pulmonary hypertension. The signaling cascade through Akt, comprised of three isoforms (Akt1–3) with distinct but overlapping functions, is involved in regulating cell proliferation and migration. This study aims to investigate whether the Akt/mammalian target of rapamycin (mTOR) pathway, and particularly which Akt isoform, contributes to the development and progression of pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension (HPH). Compared with the wild-type littermates, Akt1−/− mice were protected against the development and progression of chronic HPH, whereas Akt2−/− mice did not demonstrate any significant protection against the development of HPH. Furthermore, pulmonary vascular remodeling was significantly attenuated in the Akt1−/− mice, with no significant effect noted in the Akt2−/− mice after chronic exposure to normobaric hypoxia (10% O2). Overexpression of the upstream repressor of Akt signaling, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), and conditional and inducible knockout of mTOR in smooth muscle cells were also shown to attenuate the rise in right ventricular systolic pressure and the development of right ventricular hypertrophy. In conclusion, Akt isoforms appear to have a unique function within the pulmonary vasculature, with the Akt1 isoform having a dominant role in pulmonary vascular remodeling associated with HPH. The PTEN/Akt1/mTOR signaling pathway will continue to be a critical area of study in the pathogenesis of pulmonary hypertension, and specific Akt isoforms may help specify therapeutic targets for the treatment of pulmonary hypertension. PMID:25416384

Serotonin Signaling Through the 5-HT1B Receptor and NADPH Oxidase 1 in Pulmonary Arterial Hypertension.

PubMed

Hood, Katie Y; Mair, Kirsty M; Harvey, Adam P; Montezano, Augusto C; Touyz, Rhian M; MacLean, Margaret R

2017-07-01

Serotonin can induce human pulmonary artery smooth muscle cell (hPASMC) proliferation through reactive oxygen species (ROS), influencing the development of pulmonary arterial hypertension (PAH). We hypothesize that in PASMCs, serotonin induces oxidative stress through NADPH-oxidase-derived ROS generation and reduced Nrf-2 (nuclear factor [erythroid-derived 2]-like 2) antioxidant systems, promoting vascular injury. HPASMCs from controls and PAH patients, and PASMCs from Nox1 -/- mice, were stimulated with serotonin in the absence/presence of inhibitors of Src kinase, the 5-HT 1B receptor, and NADPH oxidase 1 (Nox1). Markers of fibrosis were also determined. The pathophysiological significance of our findings was examined in vivo in serotonin transporter overexpressing female mice, a model of pulmonary hypertension. We confirmed thatserotonin increased superoxide and hydrogen peroxide production in these cells. For the first time, we show that serotonin increased oxidized protein tyrosine phosphatases and hyperoxidized peroxiredoxin and decreased Nrf-2 and catalase activity in hPASMCs. ROS generation was exaggerated and dependent on cellular Src-related kinase, 5-HT 1B receptor, and the serotonin transporter in human pulmonary artery smooth muscle cells from PAH subjects. Proliferation and extracellular matrix remodeling were exaggerated in human pulmonary artery smooth muscle cells from PAH subjects and dependent on 5-HT 1B receptor signaling and Nox1, confirmed in PASMCs from Nox1 -/- mice. In serotonin transporter overexpressing mice, SB216641, a 5-HT 1B receptor antagonist, prevented development of pulmonary hypertension in a ROS-dependent manner. Serotonin can induce cellular Src-related kinase-regulated Nox1-induced ROS and Nrf-2 dysregulation, contributing to increased post-translational oxidative modification of proteins and activation of redox-sensitive signaling pathways in hPASMCs, associated with mitogenic responses. 5-HT 1B receptors contribute to experimental pulmonary hypertension by inducing lung ROS production. Our results suggest that 5-HT 1B receptor-dependent cellular Src-related kinase-Nox1-pathways contribute to vascular remodeling in PAH. © 2017 The Authors.

Serotonin Signaling Through the 5-HT1B Receptor and NADPH Oxidase 1 in Pulmonary Arterial Hypertension

PubMed Central

Hood, Katie Y.; Mair, Kirsty M.; Harvey, Adam P.; Montezano, Augusto C.; Touyz, Rhian M.

2017-01-01

Objective— Serotonin can induce human pulmonary artery smooth muscle cell (hPASMC) proliferation through reactive oxygen species (ROS), influencing the development of pulmonary arterial hypertension (PAH). We hypothesize that in PASMCs, serotonin induces oxidative stress through NADPH-oxidase–derived ROS generation and reduced Nrf-2 (nuclear factor [erythroid-derived 2]-like 2) antioxidant systems, promoting vascular injury. Approach and Results— HPASMCs from controls and PAH patients, and PASMCs from Nox1−/− mice, were stimulated with serotonin in the absence/presence of inhibitors of Src kinase, the 5-HT1B receptor, and NADPH oxidase 1 (Nox1). Markers of fibrosis were also determined. The pathophysiological significance of our findings was examined in vivo in serotonin transporter overexpressing female mice, a model of pulmonary hypertension. We confirmed thatserotonin increased superoxide and hydrogen peroxide production in these cells. For the first time, we show that serotonin increased oxidized protein tyrosine phosphatases and hyperoxidized peroxiredoxin and decreased Nrf-2 and catalase activity in hPASMCs. ROS generation was exaggerated and dependent on cellular Src-related kinase, 5-HT1B receptor, and the serotonin transporter in human pulmonary artery smooth muscle cells from PAH subjects. Proliferation and extracellular matrix remodeling were exaggerated in human pulmonary artery smooth muscle cells from PAH subjects and dependent on 5-HT1B receptor signaling and Nox1, confirmed in PASMCs from Nox1−/− mice. In serotonin transporter overexpressing mice, SB216641, a 5-HT1B receptor antagonist, prevented development of pulmonary hypertension in a ROS-dependent manner. Conclusions— Serotonin can induce cellular Src-related kinase–regulated Nox1-induced ROS and Nrf-2 dysregulation, contributing to increased post-translational oxidative modification of proteins and activation of redox-sensitive signaling pathways in hPASMCs, associated with mitogenic responses. 5-HT1B receptors contribute to experimental pulmonary hypertension by inducing lung ROS production. Our results suggest that 5-HT1B receptor–dependent cellular Src-related kinase-Nox1-pathways contribute to vascular remodeling in PAH. PMID:28473438

Pulmonary Hypertension

MedlinePlus

Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have ... and you can develop heart failure. Symptoms of PH include Shortness of breath during routine activity, such ...

Pulmonary Angiography and Embolization for Severe Hemoptysis Due to Cavitary Pulmonary Tuberculosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanyika, Charles; Corr, Peter; Royston, Duncan

1999-11-15

Purpose: To identify the role of pulmonary angiography in the diagnosis and treatment of severe hemoptysis due to cavitary pulmonary tuberculosis. Methods: Selective pulmonary angiography was performed on eight patients with severe hemoptysis uncontrolled by previous bronchial and systemic arterial embolization. Results: Three (38%) patients had Rasmussen aneurysms, which were successfully embolized with steel coils. Five patients demonstrated pulmonary arterial hypoperfusion in the diseased lung. Conclusions: We recommend pulmonary angiography in cavitary tuberculous patients with severe hemoptysis who do not respond to systemic arterial embolization. Rasmussen aneurysms are effectively treated by steel coil occlusion.

Structural and immunohistochemical changes in the hepatic vascular system in compensated and decompensated stenosis of the pulmonary trunk.

PubMed

Novikov, Yu V; Shormanov, S V; Kulikov, S V

2012-01-01

Modeling of pulmonary trunk stenosis leads to an increase in hepatic vascular resistance because of veno-arterial and veno-venous reactions. During the compensation phase, bundles of intimal musculature and myoelastic sphincters appear in the arteries, while in the efferent veins hypertrophy of the muscle rolls is observed. The decompensation phase of stenosis is characterized by relaxation of hepatic vascular walls, reduction of the number of arteries with intimal muscles and sphincter structures, and atrophy of muscle rolls in hepatic veins. Sclerotic changes develop in the vascular bed. Failure of the compensatory reactions results in development of chronic hepatic venous plethora with typical morphological manifestations.

Anomalous Origin of One Pulmonary Artery From the Ascending Aorta: From Diagnosis to Treatment in Angola.

PubMed

Manuel, Valdano; Sousa-Uva, Miguel; Morais, Humberto; Magalhães, Manuel P; Pedro, Albino; Miguel, Gade; Nunes, Maria A S; Gamboa, Sebastiana; Júnior, António P F

2015-10-01

Anomalous origin of one pulmonary artery is a rare congenital heart disease in which one pulmonary artery branch originates from the ascending aorta. To describe the experience of a cardiothoracic center in an African country to repair anomalous origin of one pulmonary artery in the context of Portugal-Angola collaboration. Between March 2011 and March 2015, four consecutive patients with anomalous origin of pulmonary artery branch underwent surgical correction. The mean age was 1.6 months. The mean weight was 4 kg. All had right pulmonary artery branch originating from the ascending aorta. All patients underwent direct implantation of right pulmonary branch to main pulmonary artery. Two patents had patent ductus arteriosus and one had atrial septal defect. Two patients had pulmonary hypertension. There was no registration of death. The mean cardiopulmonary bypass time was 75.5 ± 4.5 minutes, mean aortic cross-clamping time was 40 ± 5.6 minutes, and mean duration of the postoperative intensive care unit stay was 6.8 ± 5.7 days. At discharge, one patient had residual gradient of 25 mm Hg, the remainder had no significant gradient. The mean follow-up time was 11 months (5-28 months). One week after discharge, one patient presented operative wound dehiscence. At the last follow-up, all patients were alive, and no significant residual gradient or stenosis at site of anastomosis was observed. No reintervention was required. Anomalous origin of one pulmonary artery is a rare but potentially treatable lesion if operated early in life. Direct implantation was a good technique with good short-term results. © The Author(s) 2015.

Efficacy and safety of oral sildenafil in children with Down syndrome and pulmonary hypertension.

PubMed

Beghetti, Maurice; Rudzinski, Andrzej; Zhang, Min

2017-07-04

Despite the increased risk for pulmonary hypertension in children with Down syndrome, the response to treatment with targeted therapies for pulmonary hypertension in these patients is not well characterized. The Sildenafil in Treatment-naive children, Aged 1-17 years, with pulmonary arterial hypertension (STARTS-1) trial was a dose-ranging study of the short-term efficacy and safety of oral sildenafil in children with pulmonary arterial hypertension. We assessed the safety and efficacy of oral sildenafil in children with Down syndrome and pulmonary arterial hypertension. This was a post-hoc analysis of children with Down syndrome and pulmonary arterial hypertension enrolled in the STARTS-1 trial. Mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance index (PVRI), and cardiac index (CI) were assessed at baseline and following 16 weeks of treatment with sildenafil. Of 234 patients randomized and treated in the STARTS-1 trial, 48 (20.5%) had Down syndrome. Although sildenafil produced dose-related reductions in PVRI and mPAP, compared with placebo, in non-Down syndrome patients and children developmentally able to exercise, this was not satisfactorily marked in patients with Down syndrome. The dose-related reductions in PVRI, compared with placebo, occurred in all subgroups, with the exception of the Down syndrome subgroup. Sildenafil appeared to be well tolerated in the Down syndrome subpopulation and the most frequently reported AEs were similar to those reported for the entire STARTS-1 population. Sildenafil treatment for 16 weeks had no effect on PVRI or mPAP in children with Down syndrome and pulmonary arterial hypertension. The results suggest that children with Down syndrome may be less responsive to sildenafil for pulmonary arterial hypertension, but the incomplete work-up for the etiology of pulmonary arterial hypertension may have introduced a potential bias. Study received, September 8, 2005 (retrospectively registered); Study start, August 2003; ClinicalTrials.gov identifier, NCT00159913 .

Endothelial and Smooth Muscle Cell Ion Channels in Pulmonary Vasoconstriction and Vascular Remodeling

PubMed Central

Makino, Ayako; Firth, Amy L.; Yuan, Jason X.-J.

2017-01-01

The pulmonary circulation is a low resistance and low pressure system. Sustained pulmonary vasoconstriction and excessive vascular remodeling often occur under pathophysiological conditions such as in patients with pulmonary hypertension. Pulmonary vasoconstriction is a consequence of smooth muscle contraction. Many factors released from the endothelium contribute to regulating pulmonary vascular tone, while the extracellular matrix in the adventitia is the major determinant of vascular wall compliance. Pulmonary vascular remodeling is characterized by adventitial and medial hypertrophy due to fibroblast and smooth muscle cell proliferation, neointimal proliferation, intimal, and plexiform lesions that obliterate the lumen, muscularization of precapillary arterioles, and in situ thrombosis. A rise in cytosolic free Ca2+ concentration ([Ca2+]cyt) in pulmonary artery smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction, while increased release of mitogenic factors, upregulation (or downregulation) of ion channels and transporters, and abnormalities in intracellular signaling cascades are key to the remodeling of the pulmonary vasculature. Changes in the expression, function, and regulation of ion channels in PASMC and pulmonary arterial endothelial cells play an important role in the regulation of vascular tone and development of vascular remodeling. This article will focus on describing the ion channels and transporters that are involved in the regulation of pulmonary vascular function and structure and illustrating the potential pathogenic role of ion channels and transporters in the development of pulmonary vascular disease. PMID:23733654

Improved pulmonary vascular reactivity and decreased hypertrophic remodeling during nonhypercapnic acidosis in experimental pulmonary hypertension

PubMed Central

Christou, Helen; Reslan, Ossama M.; Mam, Virak; Tanbe, Alain F.; Vitali, Sally H.; Touma, Marlin; Arons, Elena; Mitsialis, S. Alex; Kourembanas, Stella

2012-01-01

Pulmonary hypertension (PH) is characterized by pulmonary arteriolar remodeling with excessive pulmonary vascular smooth muscle cell (VSMC) proliferation. This results in decreased responsiveness of pulmonary circulation to vasodilator therapies. We have shown that extracellular acidosis inhibits VSMC proliferation and migration in vitro. Here we tested whether induction of nonhypercapnic acidosis in vivo ameliorates PH and the underlying pulmonary vascular remodeling and dysfunction. Adult male Sprague-Dawley rats were exposed to hypoxia (8.5% O2) for 2 wk, or injected subcutaneously with monocrotaline (MCT, 60 mg/kg) to develop PH. Acidosis was induced with NH4Cl (1.5%) in the drinking water 5 days prior to and during the 2 wk of hypoxic exposure (prevention protocol), or after MCT injection from day 21 to 28 (reversal protocol). Right ventricular systolic pressure (RVSP) and Fulton's index were measured, and pulmonary arteriolar remodeling was analyzed. Pulmonary and mesenteric artery contraction to phenylephrine (Phe) and high KCl, and relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined ex vivo. Hypoxic and MCT-treated rats demonstrated increased RVSP, Fulton's index, and pulmonary arteriolar thickening. In pulmonary arteries of hypoxic and MCT rats there was reduced contraction to Phe and KCl and reduced vasodilation to ACh and SNP. Acidosis prevented hypoxia-induced PH, reversed MCT-induced PH, and resulted in reduction in all indexes of PH including RVSP, Fulton's index, and pulmonary arteriolar remodeling. Pulmonary artery contraction to Phe and KCl was preserved or improved, and relaxation to ACh and SNP was enhanced in NH4Cl-treated PH animals. Acidosis alone did not affect the hemodynamics or pulmonary vascular function. Phe and KCl contraction and ACh and SNP relaxation were not different in mesenteric arteries of all groups. Thus nonhypercapnic acidosis ameliorates experimental PH, attenuates pulmonary arteriolar thickening, and enhances pulmonary vascular responsiveness to vasoconstrictor and vasodilator stimuli. Together with our finding that acidosis decreases VSMC proliferation, the results are consistent with the possibility that nonhypercapnic acidosis promotes differentiation of pulmonary VSMCs to a more contractile phenotype, which may enhance the effectiveness of vasodilator therapies in PH. PMID:22287610

Systemic rapamycin to prevent in-stent stenosis in peripheral pulmonary arterial disease: early clinical experience.

PubMed

Hallbergson, Anna; Esch, Jesse J; Tran, Trang X; Lock, James E; Marshall, Audrey C

2016-10-01

We have taken a novel approach using oral rapamycin - sirolimus - as a medical adjunct to percutaneous therapy in patients with in-stent stenosis and high risk of right ventricular failure. Peripheral pulmonary artery stenosis can result in right ventricular hypertension, dysfunction, and death. Percutaneous pulmonary artery angioplasty and stent placement acutely relieve obstructions, but patients frequently require re-interventions due to re-stenosis. In patients with tetralogy of Fallot or arteriopathy, the problem of in-stent stenosis contributes to the rapidly recurrent disease. Rapamycin was administered to 10 patients (1.5-18 years) with peripheral pulmonary stenosis and in-stent stenosis and either right ventricular hypertension, pulmonary blood flow maldistribution, or segmental pulmonary hypertension. Treatment was initiated around the time of catheterisation and continued for 1-3 months. Potential side-effects were monitored by clinical review and blood tests. Target serum rapamycin level (6-10 ng/ml) was accomplished in all patients; eight of the nine patients who returned for clinically indicated catheterisations demonstrated reduction in in-stent stenosis, and eight of the 10 patients experienced no significant side-effects. Among all, one patient developed diarrhoea requiring drug discontinuation, and one patient experienced gastrointestinal bleeding while on therapy that was likely due to an indwelling feeding tube and this patient tolerated rapamycin well following tube removal. Our initial clinical experience supports that patients with peripheral pulmonary artery stenosis can be safely treated with rapamycin. Systemic rapamycin may provide a novel medical approach to reduce in-stent stenosis.

The Effects of Hemodynamic Alterations on Lung Volumes in Fetuses with Tetralogy of Fallot: An MRI Study.

PubMed

Berger-Kulemann, Vanessa; Berger, Rudolf; Mlczoch, Elisabeth; Sternal, Daniel; Mailath-Pokorny, Mariella; Hachemian, Nilouparak; Prayer, Daniela; Weber, Michael; Salzer-Muhar, Ulrike

2015-08-01

This study assessed whether the presence of tetralogy of Fallot (TOF) affects fetal lung development and whether these fetuses are at risk of pulmonary hypoplasia (PH). Furthermore, we investigated whether the degree of the concomitant pulmonary valve (PV) stenosis or a stenosis in the branch pulmonary arteries correlates with the fetal lung volume. Lung volumetry was performed in 16 fetuses with TOF who underwent MRI between gestational weeks 21 and 35 and in 22 controls. Fetal biometric data and the diameters of the PVs were evaluated by ultrasound. PV and branch pulmonary artery diameters were standardized (z-scores), and fetal lung volume/fetal body weight (FLV/FBW) ratios (ml/g) were calculated. The mean FLV/FBW ratio (0.031 ± 0.009 ml/g) in the TOF group was statistically significantly lower than in the control group (0.041 ± 0.009 ml/g; P = 0.003). None of the fetuses with TOF met the criterion for PH. FLV did not correlate with the degree of PV stenosis, but rather with the presence of a significant stenosis in at least one branch pulmonary artery. The presence of TOF moderately affects fetal lung growth, which is apparently not dependent on the degree of the PV stenosis. However, only an additional stenosis in at least one branch pulmonary artery was associated with a small FLV, but not with PH. Thus, reduced pulmonary blood flow may be offset by additional factors, such as the ability to establish a sufficient collateral system and to alter structural vascular size and, thus, pulmonary vascular resistance.

[Hepatopulmonary syndrome and portopulmonary hypertension].

PubMed

Marcu, Cristina; Schiffer, Eduardo; Aubert, John-David; Vionnet, Julien; Yerly, Patrick; Deltenre, Pierre; Marot, Astrid

2017-08-30

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) are two frequent pulmonary complications of liver disease. Portal hypertension is a key element in the pathogenesis of both disorders, which are however distinct in terms of pathogenesis, diagnosis and treatment. HPS corresponds to an abnormal arterial oxygenation in relation with the development of intrapulmonary vascular dilatations. POPH is a pulmonary arterial hypertension in the setting of portal hypertension and elevated pulmonary vascular resistance. As both diseases are associated with an increased risk of morbidity and mortality, it is important to screen and evaluate the severity of these two disorders particularly in liver transplant candidates.

Determination of fluid extraction and osmotic conductance sigma K in the lung with hypertonic NaCl infusion. I. Theory.

PubMed

Hunter, M; Lee, J

1992-11-01

A dispersion and extraction model of the lung is developed to assess how the infusion of hypertonic saline into the pulmonary artery changes the gravimetric density of pulmonary venous blood. The dispersion analysis is built on the indicator dilution curve measured for the pulmonary circulation. The extraction model consists of microvascular and interstitial compartments separated by a permeable pulmonary endothelium. Because the density of fluid extracted by the hypertonic disturbance is lower than the blood density, the extraction leads to a decrease in blood density. Two cases of fluid extraction are analyzed, a hypertonic infusion to elevate the osmotic pressure in the pulmonary arterial blood in the form of a step function and an infusion performed over a period of 1 sec. Both cases show that the dispersion significantly attenuates the changes in osmotic pressure and density as they are transported by the blood along the pulmonary vasculature. Because the model has taken into account the effect of dispersion and pulmonary blood flow, the equations developed here provide the basis to calculate from the density change in pulmonary venous blood the characteristics of osmotic extraction intrinsic to the lung.

New Concepts in the Invasive and Non Invasive Evaluation of Remodelling of the Right Ventricle and Pulmonary Vasculature in Pulmonary Arterial Hypertension

PubMed Central

Domingo, Enric; Aguilar, Rio; López-Meseguer, Manuel; Teixidó, Gisela; Vazquez, Manuel; Roman, Antonio

2009-01-01

Pulmonary arterial hypertension (PAH) is a rare fatal disease defined as a sustained elevation of pulmonary arterial pressure to more than 25 mmHg at rest, with a mean pulmonary-capillary wedge pressure and left ventricular enddiastolic pressure of less than 15 mmHg at rest. Histopathology of PAH is founded on structural modifications on the vascular wall of small pulmonary arteries characterized by thickening of all its layers. These changes, named as vascular remodelling, include vascular proliferation, fibrosis, and vessel obstruction. In clinical practice the diagnosis of PAH relies on measurements of pulmonary vascular pressure and cardiac output, and calculation of pulmonary vascular resistances. Direct evaluation of pulmonary vascular structure is not routinely performed in pulmonary hypertension since current imaging techniques are limited and since little is known about the relationship between structural changes and functional characteristics of the pulmonary vasculature. Intravascular ultrasound studies in patients with pulmonary hypertension have shown a thicker middle layer, increased wall-thickness ratio and diminished pulsatility than in control patients. Optical Coherence Tomography, a new high resolution imaging modality that has proven its superiority over intravascular ultrasound (IVUS) for the detection and characterization of coronary atherosclerotic plaque composition, may potentially be a useful technique for the in vivo study of the pulmonary arterial wall. In addition current progress in Echo Doppler technique will quantify right ventricular function with parameters independent of loading conditions and not requiring volumetric approximations of the complex geometry of the right ventricle. This would allow the in vivo study of right ventricular and pulmonary artery remodelling in PAH. PMID:19452037

[Patterns, predictors, and personalization in pulmonary arterial hypertension].

PubMed

Kawut, Steven M

2014-06-01

Epidemiologic patterns of pulmonary arterial hypertension differ by era and region and may shed light on the pathophysiology and treatment of the disease. New efforts to target one or more of the recently studied therapies could establish personalized medicine as standard care in pulmonary arterial hypertension.

Diagnosis, Evaluation and Treatment of Pulmonary Arterial Hypertension in Children

PubMed Central

Frank, Benjamin S.

2018-01-01

Pulmonary Hypertension (PH), the syndrome of elevated pressure in the pulmonary arteries, is associated with significant morbidity and mortality for affected children. PH is associated with a wide variety of potential underlying causes, including cardiac, pulmonary, hematologic and rheumatologic abnormalities. Regardless of the cause, for many patients the natural history of PH involves progressive elevation in pulmonary arterial resistance and pressure, right ventricular dysfunction, and eventually heart failure. In recent years, a number of pulmonary arterial hypertension (PAH)-targeted therapies have become available to reduce pulmonary artery pressure and improve outcome. A growing body of evidence in both the adult and pediatric literature demonstrates enhanced quality of life, functional status, and survival among treated patients. This review provides a description of select etiologies of PH seen in pediatrics and an update on the most recent data pertaining to evaluation and management of children with PH/PAH. The available evidence for specific classes of PAH-targeted therapies in pediatrics is additionally discussed. PMID:29570688

Pulmonary Artery Pseudoaneurysm Secondary to Lung Inf lammation.

PubMed

Ishimoto, Shinichirou; Sakurai, Hiroyuki; Higure, Ryouta; Kawachi, Riken; Shimamura, Mie

2018-01-15

Pulmonary artery aneurysms (PAA) and pseudoaneurysms (PAP) are caused by infections, vasculitis, trauma, pulmonary hypertension, congenital heart disease, and connective tissue disease. Most cases of such aneurysm occur in the trunk or major branches of the pulmonary artery, while the peripheral type is less common. The treatment modalities are medical therapy, surgery, and percutaneous catheter embolization. The mortality rate associated with rupture is approximately 50%. We encountered a case of a 53-year-old man with a pulmonary artery pseudoaneurysm secondary to pneumonia and cavity formation during chemotherapy for acute myeloid leukemia (AML). In diagnosis, contrast-enhanced chest computed tomography (CT) scan and pulmonary angiography were very useful. He was treated with right middle and lower lobectomy. After 1-month follow-up, he could restart additional chemotherapy.

Impact of Major Pulmonary Resections on Right Ventricular Function: Early Postoperative Changes.

PubMed

Elrakhawy, Hany M; Alassal, Mohamed A; Shaalan, Ayman M; Awad, Ahmed A; Sayed, Sameh; Saffan, Mohammad M

2018-01-15

Right ventricular (RV) dysfunction after pulmonary resection in the early postoperative period is documented by reduced RV ejection fraction and increased RV end-diastolic volume index. Supraventricular arrhythmia, particularly atrial fibrillation, is common after pulmonary resection. RV assessment can be done by non-invasive methods and/or invasive approaches such as right cardiac catheterization. Incorporation of a rapid response thermistor to pulmonary artery catheter permits continuous measurements of cardiac output, right ventricular ejection fraction, and right ventricular end-diastolic volume. It can also be used for right atrial and right ventricular pacing, and for measuring right-sided pressures, including pulmonary capillary wedge pressure. This study included 178 patients who underwent major pulmonary resections, 36 who underwent pneumonectomy assigned as group (I) and 142 who underwent lobectomy assigned as group (II). The study was conducted at the cardiothoracic surgery department of Benha University hospital in Egypt; patients enrolled were operated on from February 2012 to February 2016. A rapid response thermistor pulmonary artery catheter was inserted via the right internal jugular vein. Preoperatively the following was recorded: central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac output, right ventricular ejection fraction and volumes. The same parameters were collected in fixed time intervals after 3 hours, 6 hours, 12 hours, 24 hours, and 48 hours postoperatively. For group (I): There were no statistically significant changes between the preoperative and postoperative records in the central venous pressure and mean arterial pressure; there were no statistically significant changes in the preoperative and 12, 24, and 48 hour postoperative records for cardiac index; 3 and 6 hours postoperative showed significant changes. There were statistically significant changes between the preoperative and postoperative records for heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction and right ventricular end diastolic volume index, in all postoperative records. For group (II): There were no statistically significant changes between the preoperative and all postoperative records for the central venous pressure, mean arterial pressure and cardiac index. There were statistically significant changes between the preoperative and postoperative records for heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction and right ventricular end diastolic volume index in all postoperative records. There were statistically significant changes between the two groups in all postoperative records for heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction and right ventricular end diastolic volume index. There is right ventricular dysfunction early after major pulmonary resection caused by increased right ventricular afterload. This dysfunction is more present in pneumonectomy than in lobectomy. Heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction, and right ventricular end diastolic volume index are significantly affected by pulmonary resection.

Effects of atorvastatin and losartan on monocrotaline-induced pulmonary artery remodeling in rats.

PubMed

Xie, Liangdi; Lin, Peisen; Xie, Hong; Xu, Changsheng

2010-01-01

Structural remodeling of pulmonary artery plays an important role in maintaining sustained pulmonary arterial hypertension (PAH). The anti-remodeling effects of statins have been reported in systemic hypertension. In this study, we studied the effects of atovastatin (Ato) or losartan (Los) in monocrotaline (MCL)-induced pulmonary artery remodeling using a rat model. Forty Sprague-Dawley (SD) rats were randomly assigned into four groups (n = 10): normal control (Ctr), PAH, PAH treated with Los, and PAH treated with Ato. We found that in the Los- or Ato-treated group, the mean pulmonary arterial pressure, right heart hypertrophy index, ratio of wall/lumen thickness (WT%), as well as the wall/lumen area (WA%) were significantly reduced compared to the PAH group. Also in pulmonary arteries dissected from rats in the Ato- or Los-treated group, in both mRNA and protein levels, the expression of α1C subunit of voltage-gated calcium channel (Ca(v)α1c) was downregulated, while sarcoplasmic/endoplasmic reticulum calcium-ATPase (SERCA-2a) and inositol 1,4,5 triphosphate receptor 1 (IP3R-1) upregulated. However, the mRNA level of RyR-3 subunit of calcium regulating channel was increased, whereas its protein level was reduced in the treated groups. Our results suggest that atorvastatin or losartan may regress the remodeling of the pulmonary artery in pulmonary hypertensive rats, with differential expression of calcium regulating channels.

ALCAPA and massive pulmonary atelectasis: how a stent in the airway can be life-saving.

PubMed

Serio, Paola; Chiappa, Enrico; Fainardi, Valentina; Favilli, Silvia; Murzi, Bruno; Baggi, Roberto; Arcieri, Luigi; Leone, Roberto; Mirabile, Lorenzo

2014-11-01

Anomalous left coronary artery from pulmonary artery (ALCAPA) is a rare congenital anomaly in which left coronary artery arises from the pulmonary artery resulting in progressive myocardial ischemia and dysfunction of the left ventricle. We report a case of ALCAPA with severe cardiac and respiratory failure and huge heart dilation compressing the left main bronchus and preventing from an effective ventilation. Emergency bronchial stenting allowed to improve left lung atelectasis, reduce pulmonary hypertension, resume anterograde left coronary artery perfusion and stabilize cardiovascular conditions to undertake a successful surgical correction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Anomalous Systemic Artery to the Left Lower Lobe: Literature Review and a New Surgical Technique.

PubMed

Miller, Jacob R; Lancaster, Timothy S; Abarbanell, Aaron M; Manning, Peter B; Eghtesady, Pirooz

2018-05-01

Anomalous systemic arterial supply to the basal segments of the left lower lobe without coexisting pulmonary artery connection is a rare anomaly. Most feel treatment is necessary; however, the ideal strategy is unclear. Treatments described include embolization, pulmonary resection, or anastomosis to the native pulmonary artery. We recently encountered an infant with this anomaly and present a literature review summarizing all recent reports. Additionally, we describe a novel surgical technique to create a tension-free anastomosis utilizing segmental aortic translocation that we employed in our patient due to a large distance between the anomalous vessel and native left pulmonary artery.

Wave reflections in the pulmonary arteries analysed with the reservoir–wave model

PubMed Central

Bouwmeester, J Christopher; Belenkie, Israel; Shrive, Nigel G; Tyberg, John V

2014-01-01

Conventional haemodynamic analysis of pressure and flow in the pulmonary circulation yields incident and reflected waves throughout the cardiac cycle, even during diastole. The reservoir–wave model provides an alternative haemodynamic analysis consistent with minimal wave activity during diastole. Pressure and flow in the main pulmonary artery were measured in anaesthetized dogs and the effects of hypoxia and nitric oxide, volume loading and positive end-expiratory pressure were observed. The reservoir–wave model was used to determine the reservoir contribution to pressure and flow and once subtracted, resulted in ‘excess’ quantities, which were treated as wave-related. Wave intensity analysis quantified the contributions of waves originating upstream (forward-going waves) and downstream (backward-going waves). In the pulmonary artery, negative reflections of incident waves created by the right ventricle were observed. Overall, the distance from the pulmonary artery valve to this reflection site was calculated to be 5.7 ± 0.2 cm. During 100% O2 ventilation, the strength of these reflections increased 10% with volume loading and decreased 4% with 10 cmH2O positive end-expiratory pressure. In the pulmonary arterial circulation, negative reflections arise from the junction of lobar arteries from the left and right pulmonary arteries. This mechanism serves to reduce peak systolic pressure, while increasing blood flow. PMID:24756638

Pulmonary hypertension associated with left-sided heart disease.

PubMed

Maeder, Micha Tobias; Schoch, Otto D; Kleiner, Rebekka; Joerg, Lucas; Weilenmann, Daniel; Swiss Society For Pulmonary Hypertension

2017-01-19

Pulmonary hypertension associated with left-sided heart disease (PH-LHD) is the most common type of pulmonary hypertension. In patients with left-sided heart disease, the presence of pulmonary hypertension is typically a marker of more advanced disease, more severe symptoms, and worse prognosis. In contrast to pulmonary arterial hypertension, PH-LHD is characterised by an elevated pulmonary artery wedge pressure (postcapillary pulmonary hypertension) without or with an additional precapillary component (isolated postcapillary versus combined postcapillary and precapillary pulmonary hypertension). Transthoracic echocardiography is the primary nonin-vasive imaging tool to estimate the probability of pulmonary hypertension and to establish a working diagnosis on the mechanism of pulmonary hyperten-sion. However, right heart catheterisation is always required if significant pulmonary hypertension is sus-pected and exact knowledge of the haemodynamic constellation is necessary. The haemodynamic con-stellation (mean pulmonary artery pressure, mean pulmonary artery wedge pressure, left ventricular end-diastolic pressure) in combination with clinical infor-mation and imaging findings (mainly echocardiog-raphy, coronary angiography and cardiac magnetic resonance imaging) will usually allow the exact mech-anism underlying PH-LHD to be defined, which is a prerequisite for appropriate treatment. The general principle for the management of PH-LHD is to treat the underlying left-sided heart disease in an optimal man-ner using drugs and/or interventional or surgical ther-apy. There is currently no established indication for pulmonary arterial hypertension-specific therapies in PH-LHD, and specific therapies may even cause harm in patients with PH-LHD.

Pathophysiological effect of fat embolism in a canine model of pulmonary contusion.

PubMed

Elmaraghy, A W; Aksenov, S; Byrick, R J; Richards, R R; Schemitsch, E H

1999-08-01

The objective of this study was to determine the individual and combined effects of pulmonary contusion and fat embolism on the hemodynamics and pulmonary pathophysiology in a canine model of acute traumatic pulmonary injury. After a thoracotomy, twenty-one skeletally mature dogs were randomly assigned to one of three groups. Unilateral pulmonary contusion alone was produced in Group 1 (seven dogs); pulmonary contusion and fat embolism, in Group 2 (seven dogs); and fat embolism alone, in Group 3 (seven dogs). Pulmonary contusion was produced by standardized compression of the left lung with a piezoelectric force transducer. Fat embolism was produced by femoral and tibial reaming followed by pressurization of the intramedullary canals. Cardiac output, systolic blood pressure, peak airway pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, partial pressure of arterial oxygen, and partial pressure of carbon dioxide were monitored for all groups. From these data, several outcome parameters were calculated: total thoracic compliance, alveolar-arterial oxygen gradient, and ratio of partial pressure of arterial oxygen to fractional inspired oxygen concentration. All of the dogs were killed after eight hours, and tissue samples were obtained from the brain, kidneys, and lungs for histological analysis. Lung samples were assigned scores for pulmonary edema (the presence of fluid in the alveoli) and inflammation (the presence of neutrophils or hyaline membranes, or both). The percentage of the total area occupied by fat was determined. Pulmonary contusion alone caused a significant increase in the alveolar-arterial oxygen gradient but only after seven hours (p = 0.034). Fat embolism alone caused a significant transient decrease in systolic blood pressure (p = 0.001) and a significant transient increase in pulmonary arterial pressure (p = 0.01) and pulmonary capillary wedge pressure (p = 0.015). Fat embolism alone also caused a significant sustained decrease in the ratio of partial pressure of arterial oxygen to fractional inspired oxygen concentration (p = 0.0001) and a significant increase in the alveolar-arterial oxygen gradient (p = 0.0001). The combination of pulmonary contusion and fat embolism caused a significant transient increase in pulmonary capillary wedge pressure (p = 0.0013) as well as a significant sustained decrease in partial pressure of arterial oxygen (p = 0.0001) and a significant decrease in systolic blood pressure (p = 0.001) that lasted for an hour. Pulmonary contusion followed by fat embolism caused a significant increase in peak airway pressure (p = 0.015), alveolar-arterial oxygen gradient (p = 0.0001), and pulmonary arterial pressure (p = 0.01), and these effects persisted for five hours. Total thoracic compliance was decreased 6.4 percent by pulmonary contusion alone, 4.6 percent by fat embolism alone, and 23.5 percent by pulmonary contusion followed by fat embolism. The ratio of partial pressure of arterial oxygen to fractional inspired oxygen concentration was decreased 23.7 percent by pulmonary contusion alone, 52.3 percent by fat embolism alone, and 65.8 percent by pulmonary contusion followed by fat embolism. The mean pulmonary edema score was significantly higher with the combined injury than with either injury alone (p = 0.0001). None of the samples from the lungs demonstrated inflammation. Fat embolism combined with pulmonary contusion resulted in a significantly greater mean percentage of the area occupied by fat in the noncontused right lung than in the contused left lung (p = 0.001); however, no significant difference between the right and left lungs could be detected with fat embolism alone. The mean percentage of the glomerular and cerebral areas occupied by fat was greater with fat embolism combined with pulmonary contusion than with fat embolism alone (p = 0.0001 and p = 0.01, respectively). (ABSTRACT TRUNCATED)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamoda, Haitham, E-mail: haithamhamoda@hotmail.co; Tait, P.; Edmonds, D. K.

We report a 44-year-old woman who developed a fatal pulmonary embolus after uterine artery fibroid embolisation (UAE). Bilateral UAE was carried out through a single right-femoral artery puncture. The largest fibroid in the anterior fundal wall measured 4.5 cm, and the largest fibroid in the posterior fundal wall measured 6 cm. The appearances after UAE were satisfactory, and the procedure was apparently uneventful. No immediate complications were noted. The patient developed sudden-onset shortness of breath and went into cardiac arrest 19 h after the procedure. Postmortem autopsy confirmed that the cause of a death was a pulmonary embolism. To ourmore » knowledge this is the first reported case in the United Kingdom in which death occurred from a pulmonary embolus after UAE.« less

Contribution of reactive oxygen species to the pathogenesis of pulmonary arterial hypertension

PubMed Central

Naik, Jay S.; Weise-Cross, Laura; Detweiler, Neil D.; Herbert, Lindsay M.; Yellowhair, Tracylyn R.; Resta, Thomas C.

2017-01-01

Pulmonary arterial hypertension is associated with a decreased antioxidant capacity. However, neither the contribution of reactive oxygen species to pulmonary vasoconstrictor sensitivity, nor the therapeutic efficacy of antioxidant strategies in this setting are known. We hypothesized that reactive oxygen species play a central role in mediating both vasoconstrictor and arterial remodeling components of severe pulmonary arterial hypertension. We examined the effect of the chemical antioxidant, TEMPOL, on right ventricular systolic pressure, vascular remodeling, and enhanced vasoconstrictor reactivity in both chronic hypoxia and hypoxia/SU5416 rat models of pulmonary hypertension. SU5416 is a vascular endothelial growth factor receptor antagonist and the combination of chronic hypoxia/SU5416 produces a model of severe pulmonary arterial hypertension with vascular plexiform lesions/fibrosis that is not present with chronic hypoxia alone. The major findings from this study are: 1) compared to hypoxia alone, hypoxia/SU5416 exposure caused more severe pulmonary hypertension, right ventricular hypertrophy, adventitial lesion formation, and greater vasoconstrictor sensitivity through a superoxide and Rho kinase-dependent Ca2+ sensitization mechanism. 2) Chronic hypoxia increased medial muscularization and superoxide levels, however there was no effect of SU5416 to augment these responses. 3) Treatment with TEMPOL decreased right ventricular systolic pressure in both hypoxia and hypoxia/SU5416 groups. 4) This effect of TEMPOL was associated with normalization of vasoconstrictor responses, but not arterial remodeling. Rather, medial hypertrophy and adventitial fibrotic lesion formation were more pronounced following chronic TEMPOL treatment in hypoxia/SU5416 rats. Our findings support a major role for reactive oxygen species in mediating enhanced vasoconstrictor reactivity and pulmonary hypertension in both chronic hypoxia and hypoxia/SU5416 rat models, despite a paradoxical effect of antioxidant therapy to exacerbate arterial remodeling in animals with severe pulmonary arterial hypertension in the hypoxia/SU5416 model. PMID:28666030

Protection of pulmonary graft from thrombosis in donation after cardiac death: effect of warm ischaemia versus cold ischaemia.

PubMed

Pierre, Leif; Lindstedt, Sandra; Ingemansson, Richard

2016-11-01

The use of donation after cardiac death (DCD) to overcome organ shortage is slowly moving into the clinic. In this study, we compare the protective effect of warm ischaemia versus cold ischaemia on thrombotic formation in non-heparinized pulmonary grafts. Twelve Landrace pigs were randomized into two groups: warm ischaemia and cold ischaemia. Ventricular fibrillation without the administration of heparin was induced to mimick an uncontrolled DCD situation. The animals were then exposed to either 1 h of cold ischaemia (insertion of drain and installation of cold fluid in the pleuras) or warm ischaemia (body temperature). After 1 h, the pulmonary artery was opened and the pulmonary arterial branches were then macroscopically studied for thrombotic material. After 60 min, the temperature was 36.6 ± 0.0°C in the warm ischaemic group and 14.6 ± 0.1°C in the cold ischaemic group (P < 0.001). In the warm ischaemic group, no thrombotic material could be found in the pulmonary artery in the animals examined and in the cold ischaemic group 6.8 ± 0.2 ml thrombotic material was found in the pulmonary artery (P < 0.001). In the warm ischaemic group, no thrombotic material could be found in the arterial branches of the pulmonary artery and in the cold ischaemic group 2.3 ± 0.1 ml thrombotic material was found in the arterial branches of the pulmonary artery (P < 0.001). Warm ischaemia rather than cold ischaemia seems to protect the pulmonary graft from thrombosis in uncontrolled non-heparinized DCD pigs. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: possible involvement of angiotensin-converting enzyme-2.

PubMed

Han, Su-Xia; He, Guang-Ming; Wang, Tao; Chen, Lei; Ning, Yun-Ye; Luo, Feng; An, Jin; Yang, Ting; Dong, Jia-Jia; Liao, Zeng-Lin; Xu, Dan; Wen, Fu-Qiang

2010-05-15

Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.

Oestrogen receptor alpha in pulmonary hypertension.

PubMed

Wright, Audrey F; Ewart, Marie-Ann; Mair, Kirsty; Nilsen, Margaret; Dempsie, Yvonne; Loughlin, Lynn; Maclean, Margaret R

2015-05-01

Pulmonary arterial hypertension (PAH) occurs more frequently in women with mutations in bone morphogenetic protein receptor type 2 (BMPR2) and dysfunctional BMPR2 signalling underpinning heritable PAH. We have previously shown that serotonin can uncover a pulmonary hypertensive phenotype in BMPR2(+/-) mice and that oestrogen can increase serotinergic signalling in human pulmonary arterial smooth muscle cells (hPASMCs). Hence, here we wished to characterize the expression of oestrogen receptors (ERs) in male and female human pulmonary arteries and have examined the influence of oestrogen and serotonin on BMPR2 and ERα expression. By immunohistochemistry, we showed that ERα, ERβ, and G-protein-coupled receptors are expressed in human pulmonary arteries localizing mainly to the smooth muscle layer which also expresses the serotonin transporter (SERT). Protein expression of ERα protein was higher in female PAH patient hPASMCs compared with male and serotonin also increased the expression of ERα. 17β-estradiol induced proliferation of hPASMCs via ERα activation and this engaged mitogen-activated protein kinase and Akt signalling. Female mice over-expressing SERT (SERT(+) mice) develop PH and the ERα antagonist MPP attenuated the development of PH in normoxic and hypoxic female SERT(+) mice. The therapeutic effects of MPP were accompanied by increased expression of BMPR2 in mouse lung. ERα is highly expressed in female hPASMCs from PAH patients and mediates oestrogen-induced proliferation of hPASMCs via mitogen-activated protein kinase and Akt signalling. Serotonin can increase ERα expression in hPASMCs and antagonism of ERα reverses serotonin-dependent PH in the mouse and increases BMPR2 expression. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han Suxia; He Guangming; Wang Tao

Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along withmore » increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.« less

[Blood supply of pulmonary metastases and its clinical significance].

PubMed

Jiang, Guo-Min; Zhao, Jin-Wei; Chen, Ya-Xian; Tian, Feng

2006-07-01

Interventional treatment has been widely applied to primary lung carcinoma, but seldom applied to pulmonary metastases because the blood supply of pulmonary metastases has rarely been investigated, and the present understanding is controversial. This study was to explore the correlation of the clinical value of bronchial arterial chemotherapeutic infusion (BAI) combined bronchial arterial embolization (BAE) to the blood supply of pulmonary metastases. Bronchial artery angiography was performed on 33 patients with pulmonary metastases to assess the blood supply and the distribution of pulmonary metastases. BAI was performed on hypovascular nodules, and BAE was performed on hypervascular nodules. Of the 89 metastatic nodules in the lungs of 33 patients, 63 (70.8%) were located in the mid-medial zone, and 26 (29.3%) in the lateral region of the lung; 56 had abundant blood supply, and 33 had poor blood supply. The blood supply of pulmonary metastases was correlated to the location of metastatic nodules. Most nodules in the mid-medial region had abundant blood supply, while most nodules in the lateral region had poor or had no blood supply (P<0.01). The blood supply of bronchial artery had no correlation to the volume of metastatic nodule (P>0.05). The curative efficacy of BAI and BAE was correlated to the blood supply of bronchial artery. The response rate was significantly higher in the hypervascular nodules treated with BAE than in the hypovascular nodules treated with BAI (71.4% vs. 42.4%, P<0.01). Most pulmonary metastases of hepatic cancer were hypervascular and the lipiodol deposited well in the nodules; during the follow-up, the nodules shrunk significantly and kept stable. Bronchial artery is the major feeding artery of pulmonary metastases. BAI and BAE are effective in treating pulmonary metastases with abundant blood supply.

Severe pulmonary arterial hypertension due to Angiostrongylosus vasorum in a dog

PubMed Central

Nicolle, Audrey P.; Chetboul, Valérie; Tessier-Vetzel, Dominique; Sampedrano, Carolina Carlos; Aletti, Edouard; Pouchelon, Jean-Louis

2006-01-01

A dog was presented with a history of dyspnea, coughing, and ascites. Angiostrongylosis and severe pulmonary arterial hypertension (PAH) were found, as well as a marked discordance between the electrical and mechanical events of the heart. Pulmonary arterial hypertension related to Angiostrongylus vasorum has rarely been reported. PMID:16933559

A Rare Case of Pulmonary Artery Sling with the VACTERL Association in a 20-Month-Old Infant.

PubMed

Ghandi, Yazdan; Shafiee, Akbar; Sharifi, Mehrazad; Bolandnazar, Najmeh Sadat

2017-07-01

The VACTERL association, co-occurrence of vertebral, anorectal, cardiac, tracheoesophageal, genitourinary, and limb malformations, is a rare congenital anomaly. Several cardiac anomalies have been reported as a part of the VACTERL association, particularly ventricular and atrial septal defects. Pulmonary artery sling is a rare congenital abnormality in which the left pulmonary artery arises from the right pulmonary artery. This anomaly is not frequently observed in the VACTERL association and has been rarely reported. A 20-month-old girl was admitted to our hospital due to pneumonia in the right lung, which had pulmonary artery sling as a part of the VACTERL association. Barium meal X-ray showed pressure effects on the esophagus, and computed tomography angiography revealed pulmonary artery sling. Pneumonia management was done. However, the parents of our patient refused to give consent for the surgical correction of this vascular anomaly. Three months after discharge from the hospital, the patient was visited, at which time the parents again refused surgery and treatment for their daughter despite our recommendations.

A Rare Case of Pulmonary Artery Sling with the VACTERL Association in a 20-Month-Old Infant

PubMed Central

Ghandi, Yazdan; Shafiee, Akbar; Sharifi, Mehrazad; Bolandnazar, Najmeh Sadat

2017-01-01

The VACTERL association, co-occurrence of vertebral, anorectal, cardiac, tracheoesophageal, genitourinary, and limb malformations, is a rare congenital anomaly. Several cardiac anomalies have been reported as a part of the VACTERL association, particularly ventricular and atrial septal defects. Pulmonary artery sling is a rare congenital abnormality in which the left pulmonary artery arises from the right pulmonary artery. This anomaly is not frequently observed in the VACTERL association and has been rarely reported. A 20-month-old girl was admitted to our hospital due to pneumonia in the right lung, which had pulmonary artery sling as a part of the VACTERL association. Barium meal X-ray showed pressure effects on the esophagus, and computed tomography angiography revealed pulmonary artery sling. Pneumonia management was done. However, the parents of our patient refused to give consent for the surgical correction of this vascular anomaly. Three months after discharge from the hospital, the patient was visited, at which time the parents again refused surgery and treatment for their daughter despite our recommendations. PMID:29062381

[The role of the adreno-cholinergic interaction in the pulmonary hemodynamics changes following myocardial ischemia].

PubMed

Evlakhov, V I; Poiasov, I Z

2014-06-01

In acute experiments in anesthetized rabbits the pulmonary hemodynamics changes were studied following 60 s myocardial ischemia in the region of the descendent left coronary artery in control state and after the blockade of M- or N-cholinoreceptors and acetylcholine infusion. Following myocardial ischemia in control animals the pulmonary artery pressure and flow decreased, the pulmonary vascular resistance was not changed. Following myocardial ischemia after the blockade of M-cholinoreceptors by atropine the changes of pulmonary hemodynamics were the same as in control animals, the cardiac output decreased twice as more as in control animals. Following myocardial ischemia after the blockade of N-cholinoreceptors by hexamethonium the pulmonary hemodynamics changes were the same as in the control rabbits. Following myocardial ischemia after the acetylcholine infusion the pulmonary artery flow decreased more than the cardiac output, the pulmonary vascular resistance was diminished. The disbalance of the cardiac output and pulmonary artery flow changes has revealed the significance of the adreno-cholinergic interaction in the changes of the pulmonary vessels capacitance and resistive functions following myocardial ischemia.

Automated assessment of aortic and main pulmonary arterial diameters using model-based blood vessel segmentation for predicting chronic thromboembolic pulmonary hypertension in low-dose CT lung screening

NASA Astrophysics Data System (ADS)

Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Sugiura, Toshihiko; Tanabe, Nobuhiro; Kusumoto, Masahiko; Eguchi, Kenji; Kaneko, Masahiro

2018-02-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by obstruction of the pulmonary vasculature by residual organized thrombi. A morphological abnormality inside mediastinum of CTEPH patient is enlargement of pulmonary artery. This paper presents an automated assessment of aortic and main pulmonary arterial diameters for predicting CTEPH in low-dose CT lung screening. The distinctive feature of our method is to segment aorta and main pulmonary artery using both of prior probability and vascular direction which were estimated from mediastinal vascular region using principal curvatures of four-dimensional hyper surface. The method was applied to two datasets, 64 lowdose CT scans of lung cancer screening and 19 normal-dose CT scans of CTEPH patients through the training phase with 121 low-dose CT scans. This paper demonstrates effectiveness of our method for predicting CTEPH in low-dose CT screening.

[Compression of trachea and esophagus by abnormal course of the left pulmonary artery (author's transl)].

PubMed

Lang, D; Hofstetter, R; Müssig, G; von Bernuth, G

1975-11-01

A three months old infant with abnormal origine and course of the left pulmonary artery is described. The course of the left pulmonary artery between oesophagus and trachea causes narrowing of the distal trachea leading to in- and expiratory stridor. A ventral indentation of the oesophagus, visible on the lateral plane of an oesophageal roentgenogram, is characteristic for the anomaly which can be proven by pulmonary angiography.

Preoperative partitioning of pulmonary vascular resistance correlates with early outcome after thromboendarterectomy for chronic thromboembolic pulmonary hypertension.

PubMed

Kim, Nick H S; Fesler, Pierre; Channick, Richard N; Knowlton, Kirk U; Ben-Yehuda, Ori; Lee, Stephen H; Naeije, Robert; Rubin, Lewis J

2004-01-06

Pulmonary thromboendarterectomy (PTE) is the preferred treatment for chronic thromboembolic pulmonary hypertension (CTEPH), but persistent pulmonary hypertension after PTE, as a result of either inaccessible distal thrombotic material or coexistent intrinsic small-vessel disease, remains a major determinant of poor outcome. Conventional preoperative evaluation is unreliable in identifying patients at risk for persistent pulmonary hypertension or predicting postoperative hemodynamic outcome. We postulated that pulmonary arterial occlusion pressure waveform analysis, a technique that has been used for partitioning pulmonary vascular resistance, might identify CTEPH patients with significant distal, small-vessel disease. Twenty-six patients underwent preoperative right heart catheterization before PTE. Pulmonary artery occlusion waveform recordings were performed in triplicate. Postoperative hemodynamics after PTE were compared with preoperative partitioning of pulmonary vascular resistance derived from the occlusion data. Preoperative assessment of upstream resistance (Rup) correlated with both postoperative total pulmonary resistance index (R2=0.79, P<0.001) and postoperative mean pulmonary artery pressure (R2=0.75, P<0.001). All 4 postoperative deaths occurred in patients with a preoperative Rup <60%. Pulmonary arterial occlusion pressure waveform analysis may identify CTEPH patients at risk for persistent pulmonary hypertension and poor outcome after PTE. Patients with CTEPH and Rup value <60% appear to be at highest risk.

Trans-pulmonary echocardiography as a guide for device closure of patent ductus arteriosus.

PubMed

Kudo, Yoshiyuki; Suda, Kenji; Yoshimoto, Hironaga; Teramachi, Yozo; Kishimoto, Shintaro; Iemura, Motofumi; Matsuishi, Toyojiro

2015-08-01

The aim of this study was to develop trans-pulmonary echocardiography (TPE) to guide device closure of patent ductus arteriosus (DC-PDA). Aortography requires a large amount of contrast yet may give us an inadequate image to evaluate anatomy or residual shunt in patients with large PDA or dilated vessels and is precluded in patients with renal dysfunction. Practically, there is no imaging modality to monitor the entire procedure except for trans-esophageal echocardiography that requires general anesthesia. Subjects were seven patients with ages ranged from 6- to 77-years old and body weight > 15 kg. The size of the PDA ranged from 1.8 to 6.3 mm with pulmonary to systemic flow ratios from 1.2 to 2.2. During DC-PDA using Ampaltzer Duct Occluder or coil, an intra-cardiac echocardiographic (ICE) catheter was advanced into pulmonary arteries and standard views were developed to guide DC-PDA. We have developed two standard views; the main pulmonary artery view (MPA view) and the left pulmonary artery view (LPA view). The MPA view provided aortic short axis view equivalent to that seen by trans-thoracic echocardiography in children. The LPA view, obtained by the echo probe in the LPA and turned it up upside down, provided long axis view of the PDA allowing more precise anatomical evaluation. TPE allowed us to monitor the entire procedure and determine residual shunts. TPE in the MPA and LPA view can be an effective guide for DC-PDA. This report leads to new application of this imaging device. © 2015 Wiley Periodicals, Inc.

Treatment for unstable pulmonary sequestration injury in patient with severe blunt trauma: A case report.

PubMed

Hiraki, Sakiko; Okada, Yohei; Arai, Yusuke; Ishii, Wataru; Iiduka, Ryoji

2017-08-01

Pulmonary sequestration is a congenital malformation characterized by nonfunctioning tissue not communicating with the tracheobronchial tree. As the blood pressure in the artery feeding the sequestrated lung tissue is higher than that in the normal pulmonary artery, the risk of massive hemorrhage in pulmonary sequestration is high. We herein present the first case of a severe blunt trauma patient with unstable pulmonary sequestration injury. The mechanism of pulmonary sequestration injury is vastly different than that of injury to normal lung. We suggest that proximal feeding artery embolization should be performed before surgical intervention in patients with massive hemorrhage of pulmonary sequestration due to severe chest trauma.

Time course of haemodynamic, respiratory and inflammatory disturbances induced by experimental acute pulmonary polystyrene microembolism.

PubMed

Dolci, Daniel T; Fuentes, Carolina B; Rolim, Denise; Park, Marcelo; Schettino, Guilherme P P; Azevedo, Luciano C P

2010-01-01

The time course of cardiopulmonary alterations after pulmonary embolism has not been clearly demonstrated and nor has the role of systemic inflammation on the pathogenesis of the disease. This study aimed to evaluate over 12 h the effects of pulmonary embolism caused by polystyrene microspheres on the haemodynamics, lung mechanics and gas exchange and on interleukin-6 production. Ten large white pigs (weight 35-42 kg) had arterial and pulmonary catheters inserted and pulmonary embolism was induced in five pigs by injection of polystyrene microspheres (diameter approximately 300 micromol l(-1)) until a value of pulmonary mean arterial pressure of twice the baseline was obtained. Five other animals received only saline. Haemodynamic and respiratory data and pressure-volume curves of the respiratory system were collected. A bronchoscopy was performed before and 12 h after embolism, when the animals were euthanized. The embolism group developed hypoxaemia that was not corrected with high oxygen fractions, as well as higher values of dead space, airway resistance and lower respiratory compliance levels. Acute haemodynamic alterations included pulmonary arterial hypertension with preserved systemic arterial pressure and cardiac index. These derangements persisted until the end of the experiments. The plasma interleukin-6 concentrations were similar in both groups; however, an increase in core temperature and a nonsignificant higher concentration of bronchoalveolar lavage proteins were found in the embolism group. Acute pulmonary embolism induced by polystyrene microspheres in pigs produces a 12-h lasting hypoxaemia and a high dead space associated with high airway resistance and low compliance. There were no plasma systemic markers of inflammation, but a higher central temperature and a trend towards higher bronchoalveolar lavage proteins were found.

Exercise-Induced Pulmonary Hypertension: Translating Pathophysiological Concepts Into Clinical Practice.

PubMed

Naeije, Robert; Saggar, Rajeev; Badesch, David; Rajagopalan, Sanjay; Gargani, Luna; Rischard, Franz; Ferrara, Francesco; Marra, Alberto M; D' Alto, Michele; Bull, Todd M; Saggar, Rajan; Grünig, Ekkehard; Bossone, Eduardo

2018-01-31

Exercise stress testing of the pulmonary circulation for the diagnosis of latent or early-stage pulmonary hypertension (PH) is gaining acceptance. There is emerging consensus to define exercise-induced PH by a mean pulmonary artery pressure > 30 mm Hg at a cardiac output < 10 L/min and a total pulmonary vascular resistance> 3 Wood units at maximum exercise, in the absence of PH at rest. Exercise-induced PH has been reported in association with a bone morphogenetic receptor-2 gene mutation, in systemic sclerosis, in left heart conditions, in chronic lung diseases, and in chronic pulmonary thromboembolism. Exercise-induced PH is a cause of decreased exercise capacity, may precede the development of manifest PH in a proportion of patients, and is associated with a decreased life expectancy. Exercise stress testing of the pulmonary circulation has to be dynamic and rely on measurements of the components of the pulmonary vascular equation during, not after exercise. Noninvasive imaging measurements may be sufficiently accurate in experienced hands, but suffer from lack of precision, so that invasive measurements are required for individual decision-making. Exercise-induced PH is caused either by pulmonary vasoconstriction, pulmonary vascular remodeling, or by increased upstream transmission of pulmonary venous pressure. This differential diagnosis is clinical. Left heart disease as a cause of exercise-induced PH can be further ascertained by a pulmonary artery wedge pressure above or below 20 mm Hg at a cardiac output < 10 L/min or a pulmonary artery wedge pressure-flow relationship above or below 2 mm Hg/L/min during exercise. Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Targeted activation of endothelin-1 exacerbates hypoxia-induced pulmonary hypertension

DOE Office of Scientific and Technical Information (OSTI.GOV)

Satwiko, Muhammad Gahan; Ikeda, Koji; Nakayama, Kazuhiko

Pulmonary arterial hypertension (PAH) is a fatal disease that eventually results in right heart failure and death. Current pharmacologic therapies for PAH are limited, and there are no drugs that could completely cure PAH. Enhanced activity of endothelin system has been implicated in PAH severity and endothelin receptor antagonists have been used clinically to treat PAH. However, there is limited experimental evidence on the direct role of enhanced endothelin system activity in PAH. Here, we investigated the correlation between endothelin-1 (ET-1) and PAH using ET-1 transgenic (ETTG) mice. Exposure to chronic hypoxia increased right ventricular pressure and pulmonary arterial wallmore » thickness in ETTG mice compared to those in wild type mice. Of note, ETTG mice exhibited modest but significant increase in right ventricular pressure and vessel wall thickness relative to wild type mice even under normoxic conditions. To induce severe PAH, we administered SU5416, a vascular endothelial growth factor receptor inhibitor, combined with exposure to chronic hypoxia. Treatment with SU5416 modestly aggravated hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial vessel wall thickening in ETTG mice in association with increased interleukin-6 expression in blood vessels. However, there was no sign of obliterative endothelial cell proliferation and plexiform lesion formation in the lungs. These results demonstrated that enhanced endothelin system activity could be a causative factor in the development of PAH and provided rationale for the inhibition of endothelin system to treat PAH. - Highlights: • Role of endothelin-1 in pulmonary arterial hypertension (PAH) was investigated. • The endothelin-1 transgenic (ETTG) and wild type (WT) mice were analyzed. • ETTG mice spontaneously developed PAH under normoxia conditions. • SU5416 further aggravated PAH in ETTG mice. • Enhanced endothelin system activity could be a causative factor in PAH development.« less

Recurrent pulmonary embolism due to echinococcosis secondary to hepatic surgery for hydatid cysts.

PubMed

Damiani, Mario Francesco; Carratù, Pierluigi; Tatò, Ilaria; Vizzino, Heleanna; Florio, Carlo; Resta, Onofrio

2012-01-01

We describe the case of a 53-year-old man with recurrent pulmonary embolism due to intra-arterial cysts from Echinococcus. Both the patient's medical history and the computed tomographic (CT) scan abnormalities led to the diagnosis. The CT scan, performed during hospitalization in our ward, showed cystic masses in the left main pulmonary artery and in the descending branch of the right pulmonary artery. Within cystic masses, thin septa were visible, giving a chambered appearance, which was suggestive of a group of daughter cysts. In the past, our patient underwent multiple operations for recurring echinococcal cysts of the liver. After the last intervention, 4 years earlier, his postoperative course was complicated by pulmonary embolism: a CT scan showed a filling defect in the descending branch of the right pulmonary artery, which was caused by the same cystic mass as 4 years later, although smaller. This mass, not properly treated, increased in diameter. Moreover, after 4 years, there has been a new episode of embolism, which involved the left main pulmonary artery. This is the first case in which there are repeated episodes of pulmonary embolism echinococcosis after hepatic surgery for removal of hydatid cysts.

Pulmonary arterial hypertension associated with chronic active Epstein-Barr virus infection.

PubMed

Hashimoto, Takahiro; Sakata, Yasushi; Fukushima, Kentaro; Maeda, Tetsuo; Arita, Yoh; Shioyama, Wataru; Nakaoka, Yoshikazu; Hori, Yumiko; Morii, Eiichi; Aozasa, Katsuyuki; Kanakura, Yuzuru; Yamauchi-Takihara, Keiko; Komuro, Issei

2011-01-01

A 45-year-old man with chronic active Epstein-Barr virus (EBV) infection (CAEBV) with natural killer cell type developed pulmonary arterial hypertension (PAH). After chemotherapy, he showed marked depression of the EBV DNA genome in the peripheral blood, but PAH sustained. He died of heart failure due to PAH, and the histo-pathological examination revealed pulmonary vascular abnormalities without lung disease on autopsy. Although the EBV DNA genome and the infiltrating lymphocytes were not detected in the lung, his clinical course suggested that his PAH might be caused by CAEBV. This is the first reported case of PAH associated CAEBV in an adult.

Pulmonary arterial hypertension associated with chronic active Epstein-Barr virus infection.

PubMed

Fukuda, Yutaka; Momoi, Nobuo; Akaihata, Mitsuko; Nagasawa, Katsutoshi; Mitomo, Masaki; Aoyagi, Yoshimichi; Endoh, Kisei; Hosoya, Mitsuaki

2015-08-01

Chronic active Epstein-Barr virus (EBV) infection (CAEBV), characterized by persistent infectious mononucleosis-like symptoms, can lead to cardiovascular complications including coronary artery aneurysm or myocarditis. Here, we present the case of an 11-year-old boy with pulmonary arterial hypertension (PAH) and junctional ectopic tachycardia associated with CAEBV. The patient did not have any major symptoms attributed to CAEBV, such as fever, lymphadenopathy or splenomegaly when the PAH developed. Mild liver dysfunction was found at the first examination, and it persisted. Two years after the PAH symptoms appeared, CAEBV was evident, based on deteriorated liver function, hepatosplenomegaly, and coronary artery aneurysms. CAEBV should be considered as a cause of secondary PAH, particularly when liver dysfunction coexists. © 2015 Japan Pediatric Society.

K(Ca)3.1 channel downregulation and impaired endothelium-derived hyperpolarization-type relaxation in pulmonary arteries from chronically hypoxic rats.

PubMed

Kroigaard, Christel; Kudryavtseva, Olga; Dalsgaard, Thomas; Wandall-Frostholm, Christine; Olesen, Søren-Peter; Simonsen, Ulf

2013-04-01

Calcium-activated potassium channels of small (K(Ca)2, SK) and intermediate (K(Ca)3.1, IK) conductance are involved in endothelium-dependent relaxation of pulmonary arteries. We hypothesized that the function and expression of K(Ca)2 and K(Ca)3.1 increase as a compensatory mechanism to counteract hypoxia-induced pulmonary hypertension in rats. For functional studies, pulmonary arteries were mounted in microvascular myographs for isometric tension recordings. The K(Ca) channel expression was evaluated by immunoblotting and quantitative PCR. Although ACh induced similar relaxations, the ACh-induced relaxations were abolished by the combined inhibition of nitric oxide synthase (by L-nitro-arginine, L-NOARG), cyclo-oxygenase (by indomethacin) and soluble guanylate cyclase (by ODQ) in pulmonary arteries from hypoxic rats, whereas 20 ± 6% (n = 8) maximal relaxation in response to ACh persisted in arteries from normoxic rats. Inhibiting Na(+),K(+)-ATPase with ouabain or blocking K(Ca)2 and K(Ca)3.1 channels reduced the persisting ACh-induced relaxation. In the presence of L-NOARG and indomethacin, a novel K(Ca)2 and K(Ca)3.1 channel activator, NS4591, induced concentration- and endothelium-dependent relaxations, which were markedly reduced in arteries from chronically hypoxic rats compared with arteries from normoxic rats. The mRNA levels of K(Ca)2.3 and K(Ca)3.1 were unaltered, whereas K(Ca)2.3 protein expression was upregulated and K(Ca)3.1 protein expression downregulated in pulmonary arteries from rats exposed to hypoxia. In conclusion, endothelium-dependent relaxation was conserved in pulmonary arteries from chronically hypoxic rats, while endothelium-derived hyperpolarization (EDH)-type relaxation was impaired in chronically hypoxic pulmonary small arteries despite upregulation of K(Ca)2.3 channels. Since impaired EDH-type relaxation was accompanied by K(Ca)3.1 channel protein downregulation, these findings suggest that K(Ca)3.1 channels are important for the maintenance of EDH-type relaxation.

Risks of on-pump coronary artery bypass grafting surgery in patients with chronic obstructive pulmonary disease due to sulfur mustard.

PubMed

Firoozabadi, Mehdi Dehghani; Sheikhi, Mohammad Ali; Rahmani, Hossein; Ebadi, Ahmad; Heidari, Amanollah; Gholizadeh, Behnam; Sharifi, Khosrow

2017-10-01

Sulfur mustard (SM) is a toxic chemical agent that belongs to a class of vesicant compounds. In the 1980s it was used by the Iraqi army against Iranian forces. Sulfur mustard severely irritates the skin, eyes and lungs. The highest side effects seen in patients affected by this gas are pulmonary complications including different types of lung diseases such as bronchiolitis. It has also led to a certain type of chronic obstructive pulmonary disease called mustard lung. Similar extra-pulmonary, molecular and hormonal effects can be observed in these patients and patients with chronic obstructive pulmonary disease. Here cardiovascular complications may be one of the most dangerous visible effects. And atherosclerosis is probable following the direct effects or consequential long-term effects of SM. The development of atherosclerosis in these patients is associated with an increased risk of cardiovascular and coronary artery disease. Coronary artery bypass grafting surgery is the treatment of coronary artery disease. Doing this surgery by bypass pump has its own morbidity and due to local and systemic inflammation changes in patients with SM pulmonary disorders it may have more side effects. Therefore, detailed knowledge of inflammatory diseases as well as the serum level or even the local lung fluid of the inflammatory factors in these patients before surgery are needed so that it would be possible to reduce the rate of morbidity and mortality by normalizing the inflammatory conditions of the patients before cardiac surgery.

[Right branch pulmonary artery stenosis with supravalvar aortic stenosis as a complication of Lecompte maneuver for tetralogy of Fallot associated with absent pulmonary valve].

PubMed

Honda, Yoshihiro; Suzuki, Shoji; Kaga, Shigeaki; Yoshida, Yukiyo; Kimura, Mitsuhiro; Kamiya, Kentaro; Sakakibara, Kenji; Katsu, Masatake

2015-05-01

The patient was diagnosed with tetralogy of Fallot associated with absent pulmonary valve syndrome and a low birth weight of 1,912 g. He suffered from respiratory distress on day 14 and received non-invasive positive pressure ventilation. At 5 months of age and 4.1 kg, he underwent intracardiac repair including right ventricular outflow repair with a monocusp patch, patch closure of the ventricular septum defect and right pulmonary transposition to the anterior of the ascending aorta following the Lecompte maneuver for airway decompression. He was subsequently discharged to home and exhibited an uneventful clinical course with non-invasive positive pressure ventilation for 5 months postoperatively. However, right pulmonary artery and supra-aortic stenosis was noted 2 years after the operation. Computed tomography (CT) and angiography showed ascending aorta strangulation by the right pulmonary artery with right ventricular outflow regurgitation. Right pulmonary artery reconstruction using polytetrafluoroethylene graft interposition and repeat right ventricular outflow repair with bicuspid hand-sewn valves was therefore performed;the postoperative course was uneventful. Pre- and post-operative management using non-invasive positive pressure ventilation and airway decompression with pulmonary artery translocation is a useful strategy in patients exhibiting symptomatic tetralogy of Fallot associated with absent pulmonary valve syndrome in the neonatal period.

Building foundations for transcatheter intervascular anastomoses: 3D anatomy of the great vessels in large experimental animals.

PubMed

Sizarov, Aleksander; de Bakker, Bernadette S; Klein, Karina; Ohlerth, Stefanie

2014-10-01

To provide comprehensive illustrations of anatomy of the relevant vessels in large experimental animals in an interactive format as preparation for developing an effective and safe transcatheter technique of aortopulmonary and bidirectional cavopulmonary intervascular anastomoses. Computed tomographic angiographic studies in two calves and two sheep were used to prepare 3D reconstructions of the aorta, pulmonary arteries, and caval and pulmonary veins. Based on these reconstructions, computer simulations of the creation of stent-enhanced aortopulmonary and bidirectional cavopulmonary anastomoses were made. We observed the following major anatomical features: (i) caudal course of the main pulmonary artery and its branches with the proximal right pulmonary artery located immediately caudal to the aortic arch, and with the central left pulmonary artery lying at a substantial distance from the descending aorta; and (ii) the distal right pulmonary artery is located dorsal to the right atrium and inferior caval vein at a substantial distance from the superior caval vein. Animations showed creation of transcatheter analogues of Waterston's and Potts' aortopulmonary shunts through placement of a covered spool-shaped stent, and the transcatheter creation of bidirectional Glenn's cavopulmonary anastomosis, by placement of a long covered trumpet-shaped stent. There are considerable differences in vascular anatomy between large experimental animals and humans. Given the need to elaborate new transcatheter techniques for intervascular anastomoses in suitable animal models before application to human, it is crucial to take these anatomical differences into account during testing and optimization of the proposed procedures. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Dextromethorphan mediated bitter taste receptor activation in the pulmonary circuit causes vasoconstriction.

PubMed

Upadhyaya, Jasbir D; Singh, Nisha; Sikarwar, Anurag S; Chakraborty, Raja; Pydi, Sai P; Bhullar, Rajinder P; Dakshinamurti, Shyamala; Chelikani, Prashen

2014-01-01

Activation of bitter taste receptors (T2Rs) in human airway smooth muscle cells leads to muscle relaxation and bronchodilation. This finding led to our hypothesis that T2Rs are expressed in human pulmonary artery smooth muscle cells and might be involved in regulating the vascular tone. RT-PCR was performed to reveal the expression of T2Rs in human pulmonary artery smooth muscle cells. Of the 25 T2Rs, 21 were expressed in these cells. Functional characterization was done by calcium imaging after stimulating the cells with different bitter agonists. Increased calcium responses were observed with most of the agonists, the largest increase seen for dextromethorphan. Previously in site-directed mutational studies, we have characterized the response of T2R1 to dextromethorphan, therefore, T2R1 was selected for further analysis in this study. Knockdown with T2R1 specific shRNA decreased mRNA levels, protein levels and dextromethorphan-induced calcium responses in pulmonary artery smooth muscle cells by up to 50%. To analyze if T2Rs are involved in regulating the pulmonary vascular tone, ex vivo studies using pulmonary arterial and airway rings were pursued. Myographic studies using porcine pulmonary arterial and airway rings showed that stimulation with dextromethorphan led to contraction of the pulmonary arterial and relaxation of the airway rings. This study shows that dextromethorphan, acting through T2R1, causes vasoconstrictor responses in the pulmonary circuit and relaxation in the airways.

In smokers, Sonic hedgehog modulates pulmonary endothelial function through vascular endothelial growth factor.

PubMed

Henno, Priscilla; Grassin-Delyle, Stanislas; Belle, Emeline; Brollo, Marion; Naline, Emmanuel; Sage, Edouard; Devillier, Philippe; Israël-Biet, Dominique

2017-05-23

Tobacco-induced pulmonary vascular disease is partly driven by endothelial dysfunction. The Sonic hedgehog (SHH) pathway is involved in vascular physiology. We sought to establish whether the SHH pathway has a role in pulmonary endothelial dysfunction in smokers. The ex vivo endothelium-dependent relaxation of pulmonary artery rings in response to acetylcholine (Ach) was compared in 34 current or ex-smokers and 8 never-smokers. The results were expressed as a percentage of the contraction with phenylephrine. We tested the effects of SHH inhibitors (GANT61 and cyclopamine), an SHH activator (SAG) and recombinant VEGF on the Ach-induced relaxation. The level of VEGF protein in the pulmonary artery ring was measured in an ELISA. SHH pathway gene expression was quantified in reverse transcriptase-quantitative polymerase chain reactions. Ach-induced relaxation was much less intense in smokers than in never-smokers (respectively 24 ± 6% and 50 ± 7% with 10 -4 M Ach; p = 0.028). All SHH pathway genes were expressed in pulmonary artery rings from smokers. SHH inhibition by GANT61 reduced Ach-induced relaxation and VEGF gene expression in the pulmonary artery ring. Recombinant VEGF restored the ring's endothelial function. VEGF gene and protein expression levels in the pulmonary artery rings were positively correlated with the degree of Ach-induced relaxation and negatively correlated with the number of pack-years. SHH pathway genes and proteins are expressed in pulmonary artery rings from smokers, where they modulate endothelial function through VEGF.

Role of Hypoxia-Induced Brain Derived Neurotrophic Factor in Human Pulmonary Artery Smooth Muscle

PubMed Central

Hartman, William; Helan, Martin; Smelter, Dan; Sathish, Venkatachalem; Thompson, Michael; Pabelick, Christina M.; Johnson, Bruce; Prakash, Y. S.

2015-01-01

Background Hypoxia effects on pulmonary artery structure and function are key to diseases such as pulmonary hypertension. Recent studies suggest that growth factors called neurotrophins, particularly brain-derived neurotrophic factor (BDNF), can influence lung structure and function, and their role in the pulmonary artery warrants further investigation. In this study, we examined the effect of hypoxia on BDNF in humans, and the influence of hypoxia-enhanced BDNF expression and signaling in human pulmonary artery smooth muscle cells (PASMCs). Methods and Results 48h of 1% hypoxia enhanced BDNF and TrkB expression, as well as release of BDNF. In arteries of patients with pulmonary hypertension, BDNF expression and release was higher at baseline. In isolated PASMCs, hypoxia-induced BDNF increased intracellular Ca2+ responses to serotonin: an effect altered by HIF1α inhibition or by neutralization of extracellular BDNF via chimeric TrkB-Fc. Enhanced BDNF/TrkB signaling increased PASMC survival and proliferation, and decreased apoptosis following hypoxia. Conclusions Enhanced expression and signaling of the BDNF-TrkB system in PASMCs is a potential mechanism by which hypoxia can promote changes in pulmonary artery structure and function. Accordingly, the BDNF-TrkB system could be a key player in the pathogenesis of hypoxia-induced pulmonary vascular diseases, and thus a potential target for therapy. PMID:26192455

Single left coronary ostium and an anomalous prepulmonic right coronary artery in 2 dogs with congenital pulmonary valve stenosis.

PubMed

Visser, Lance C; Scansen, Brian A; Schober, Karsten E

2013-06-01

A coronary artery anomaly characterized by the presence of a single left coronary ostium with absence of the right coronary ostium and an anomalous prepulmonic right coronary artery course was observed in two dogs with concurrent congenital pulmonary valve stenosis. This unique coronary artery anatomy is similar to the previously described single right coronary ostium with anomalous prepulmonic left coronary artery, the so-called type R2A anomaly, in that an anomalous coronary artery encircles the pulmonary valve annulus. Both dogs of this report, a boxer and an English bulldog, were of breeds known to be at risk for the type R2A anomaly. As such, veterinarians should be aware that the echocardiographic presence of a left coronary ostium in a dog with pulmonary valve stenosis does not exclude the possibility of a prepulmonic coronary artery anomaly that may enhance the risk of complications during balloon pulmonary valvuloplasty. A descriptive naming convention for coronary artery anomalies in dogs is also presented, which may be preferable to the older coding classification scheme. Copyright © 2013 Elsevier B.V. All rights reserved.

Coronary Artery Bypass Grafting for an Anomalous Left Coronary Artery from the Pulmonary Artery in a 73-Year-Old Female.

PubMed

Ishida, Narihiro; Shimabukuro, Katsuya; Ogura, Hiroki; Takemura, Hirofumi; Doi, Kiyoshi

2016-06-01

Anomalous left coronary artery from the pulmonary artery (ALCAPA) in adults is a rare congenital coronary abnormality. We report a case of ALCAPA in a 73-year-old female managed by total arterial revascularization. doi: 10.1111/jocs.12755 (J Card Surg 2016;31:380-382). © 2016 Wiley Periodicals, Inc.

Normal Physiological Values for Conscious Pigs Used in Biomedical Research

DTIC Science & Technology

1989-05-01

6. Cardiovascular and Pulmonary Functions........... 18 TABLE 7. Bioenergetics..................................... 19 TABLE 8. Renal Function...procedure developed in our laboratory. Plasma concentrations of aldosterone, cortisol, total T3, total T4, free T4, insulin and glucagon were...pulmonary vascular resistance , alveolar ventilation, alveolar ventilation/perfusion ratio, arterial 02 transport, tissue 02 extraction ratio, pulmonary

The effects of levosimendan exposure on oxidant/antioxidant status and trace element levels in the pulmonary artery of rats.

PubMed

Ay, Yasin; Aydın, Cemalettin; Basel, Halil; Bektaş, Hava; Bülüt, Gülay; Inan, Bekir; Ay, Nuray Kahraman; Demir, Ismail

2013-06-01

We investigated both the effect of levosimendan and the role of oxidant/antioxidant status and trace element levels in the pulmonary artery of rats. Fourteen male Wistar albino rats were randomly divided into two groups of seven animals each. Group 1 was not exposed to levosimendan and served as a control. Levosimendan (12 μg/kg) diluted in 10 ml 0.9 % NaCl was administered intraperitoneally to group 2. Animals of both groups were killed after 3 days, and their pulmonary arteries were harvested to determine changes in tissue oxidant/antioxidant status and trace element levels. The animals in both groups were killed 72 h after the levosimendan exposure treatment, and pulmonary arteries were harvested to determine levels of the lipid peroxidation product MDA and the antioxidant GSH as well as the decreased activity of antioxidant enzymes such as SOD, GSH-Px and CAT. It was found that MDA levels increased in pulmonary artery tissues of rats after levosimendan administration. The GSH level decreased in the pulmonary artery of rats after levosimendan treatment. Co, Mn, Fe, Cd and Pb levels were significantly higher (P < 0.001) and Mg, Zn and Cu levels significantly lower (P < 0.001) in the levosimendan group compared to the control group. These results suggest that levosimendan treatment caused an increase in free radical production and a decrease in antioxidant enzyme activity in the pulmonary artery of levosimendan-treated rats. It also caused a decrease or increase in the levels of many minerals in the pulmonary artery, which is an undesirable condition for normal pharmacological function.

Pulmonary MRA: differentiation of pulmonary embolism from truncation artefact.

PubMed

Bannas, Peter; Schiebler, Mark L; Motosugi, Utaroh; François, Christopher J; Reeder, Scott B; Nagle, Scott K

2014-08-01

Truncation artefact (Gibbs ringing) causes central signal drop within vessels in pulmonary magnetic resonance angiography (MRA) that can be mistaken for emboli, reducing diagnostic accuracy for pulmonary embolism (PE). We propose a quantitative approach to differentiate truncation artefact from PE. Twenty-eight patients who underwent pulmonary computed tomography angiography (CTA) for suspected PE were recruited for pulmonary MRA. Signal intensity drops within pulmonary arteries that persisted on both arterial-phase and delayed-phase MRA were identified. The percent signal loss between the vessel lumen and central drop was measured. CTA served as the reference standard for presence of pulmonary emboli. A total of 65 signal intensity drops were identified on MRA. Of these, 48 (74%) were artefacts and 17 (26%) were PE, as confirmed by CTA. Truncation artefacts had a significantly lower median signal drop than PE on both arterial-phase (26% [range 12-58%] vs. 85% [range 53-91%]) and delayed-phase MRA (26% [range 11-55%] vs. 77% [range 47-89%]), p < 0.0001 for both. Receiver operating characteristic (ROC) analyses revealed a threshold value of 51% (arterial phase) and 47% signal drop (delayed phase) to differentiate between truncation artefact and PE with 100% sensitivity and greater than 90% specificity. Quantitative signal drop is an objective tool to help differentiate truncation artefact and pulmonary embolism in pulmonary MRA. • Inexperienced readers may mistake truncation artefacts for emboli on pulmonary MRA • Pulmonary emboli have non-uniform signal drop • 51% (arterial phase) and 47% (delayed phase) cut-off differentiates truncation artefact from PE • Quantitative signal drop measurement enables more accurate pulmonary embolism diagnosis with MRA.

Mid-term outcomes of patients undergoing adjustable pulmonary artery banding

PubMed Central

Talwar, Sachin; Kamat, Neeraj Aravind; Choudhary, Shiv Kumar; Ramakrishnan, Sivasubramanian; Saxena, Anita; Juneja, Rajnish; Kothari, Shyam Sunder; Airan, Balram

2016-01-01

Objective The adjustable pulmonary artery band (APAB) has been demonstrated by us earlier to be superior to the conventional pulmonary artery banding (CPAB), in terms of reduced early morbidity and mortality. In this study, we assessed the adequacy of the band and its complications over the mid-term. Methods Between 2002 and 2012, 73 patients underwent adjustable PAB, and their operative and follow-up data were collected and analyzed. Results There was one early death following the APAB. Follow-up data were available for 57 patients of which 44 patients (61.7%) underwent definitive repair, 10 were awaiting definitive repair, and 3 patients were kept on medical follow-up because of inadequate fall in pulmonary artery (PA) pressures. 14 patients (19%) were lost to follow-up. Major PA distortion or stenosis was absent in the majority. 1 patient had pseudoaneurysm of the main pulmonary artery (MPA) with sternal sinus infection and required surgical reconstruction. 1 patient had infective endocarditis of the pulmonary valve managed medically. Band migration was not encountered. There were two deaths after definitive repair and one after APAB. Conclusions Patients undergoing APAB fulfilled the desired objectives of the pulmonary artery banding (PAB) with minimum PA complications in the mid-term. This added to the early postoperative benefits, makes the APAB an attractive alternative to the CPAB. PMID:26896271

Measurements of the pulmonary vasculature on thoracic radiographs in healthy dogs compared to dogs with mitral regurgitation.

PubMed

Oui, Heejin; Oh, Juyeon; Keh, Seoyeon; Lee, Gahyun; Jeon, Sunghoon; Kim, Hyunwook; Yoon, Junghee; Choi, Jihye

2015-01-01

This study reassessed the previously reported radiographic method of comparing pulmonary vessels versus rib diameter for differentiating healthy dogs and dogs with mitral regurgitation. The width of the right cranial pulmonary artery and vein at the fourth rib level, right caudal pulmonary artery and vein at the ninth rib level, and the diameters of the fourth rib and ninth rib were measured in prospectively recruited healthy dogs (n = 40) and retrospectively recruited dogs with mitral regurgitation (n = 58). In healthy dogs, the pulmonary arteries and accompanying veins were similar in size. The cranial lobar vessels were smaller than the fourth rib. However, 67.5% of right caudal pulmonary artery diameters and 65% of vein diameters were larger than the ninth rib in healthy dogs. The right caudal pulmonary vein diameter in dogs with mitral regurgitation, particularly those within moderate and severe grades, was significantly larger than that in healthy dogs (P < 0.001). The comparative method used to detect enlargement of the right caudal pulmonary vein relative to the accompanying pulmonary artery had the highest sensitivity (80.2%) and specificity (82.5%) for predicting mitral regurgitation. A cut-off of 1.22 when applying the ninth rib criterion had better specificity (73%) than the most used value ≤ 1 (89.7% sensitivity and 63.8% specificity), although it has less sensitivity (73%). We recommend using the accompanying pulmonary artery and 1.22 × the diameter of the ninth rib as a radiographic criterion for assessing the size of the right caudal pulmonary vein and differentiating healthy dogs from those with mitral regurgitation. © 2014 American College of Veterinary Radiology.

Pulmonary arterial capacitance in children with idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease: relation to pulmonary vascular resistance, exercise capacity, and survival.

PubMed

Sajan, Imran; Manlhiot, Cedric; Reyes, Janette; McCrindle, Brian W; Humpl, Tilman; Friedberg, Mark K

2011-09-01

Pediatric pulmonary arterial hypertension (PAH), whether idiopathic PAH (iPAH) or PAH associated with congenital heart disease (aPAH), carries high morbidity and mortality. Low pulmonary arterial capacitance (PAC), defined as right ventricular stroke volume/pulmonary artery pulse pressure, is a risk factor for mortality in adults with PAH. However, the relation of PAC to pulmonary vascular resistance (PVR), exercise endurance, and survival is poorly defined in children. Catheterization and clinical data of children with PAH (mean pulmonary artery pressure >25 mm Hg) were reviewed. Children with pulmonary shunts, stents, collaterals, or pulmonary venous hypertension were excluded. Primary outcomes were 6-minute walk distance and freedom from death/lung transplant. Forty-seven patients were studied. Nineteen (43%) had iPAH, and 28 (57%) had aPAH (7.1 ± 6.2 vs 8.4 ± 5.5 years, P = .45). Patients with iPAH had higher PVR indexed for body surface area (PVRi), lower indexed PAC (PACi), lower exercise tolerance, and lower freedom from death/lung transplant than patients with aPAH. Both higher PVRi (P < .0001) and lower PACi (P = .02) were associated with shorter 6-minute walk distance. A PACi <0.70 mL/mm Hg per square meter or >1.25 mL/mm Hg per square meter and a PVRi >13 Wood units × m(2) were associated with decreased freedom from death or lung transplant. The relationships between PVRi and PACi and survival were independent of each other and not confounded by etiologic group. Low PACi and high PVRi are independently associated with low 6-minute walk distance and survival in children with PAH. Therefore, both should be assessed for better prognostication and management in this high-risk population. Copyright © 2011 Mosby, Inc. All rights reserved.

The effect of ACE inhibition on the pulmonary vasculature in combined model of chronic hypoxia and pulmonary arterial banding in Sprague Dawley rats

NASA Astrophysics Data System (ADS)

Clarke, Shanelle; Baumgardt, Shelley; Molthen, Robert

2010-03-01

Microfocal CT was used to image the pulmonary arterial (PA) tree in rodent models of pulmonary hypertension (PH). CT images were used to measure the arterial tree diameter along the main arterial trunk at several hydrostatic intravascular pressures and calculate distensibility. High-resolution planar angiographic imaging was also used to examine distal PA microstructure. Data on pulmonary artery tree morphology improves our understanding of vascular remodeling and response to treatments. Angiotensin II (ATII) has been identified as a mediator of vasoconstriction and proliferative mitotic function. ATII has been shown to promote vascular smooth muscle cell hypertrophy and hyperplasia as well as stimulate synthesis of extracellular matrix proteins. Available ATII is targeted through angiotensin converting enzyme inhibitors (ACEIs), a method that has been used in animal models of PH to attenuate vascular remodeling and decrease pulmonary vascular resistance. In this study, we used rat models of chronic hypoxia to induce PH combined with partial left pulmonary artery occlusion (arterial banding, PLPAO) to evaluate effects of the ACEI, captopril, on pulmonary vascular hemodynamic and morphology. Male Sprague Dawley rats were placed in hypoxia (FiO2 0.1), with one group having underwent PLPAO three days prior to the chronic hypoxia. After the twenty-first day of hypoxia exposure, treatment was started with captopril (20 mg/kg/day) for an additional twenty-one days. At the endpoint, lungs were excised and isolated to examine: pulmonary vascular resistance, ACE activity, pulmonary vessel morphology and biomechanics. Hematocrit and RV/LV+septum ratio was also measured. CT planar images showed less vessel dropout in rats treated with captopril versus the non-treatment lungs. Distensibility data shows no change in rats treated with captopril in both chronic hypoxia (CH) and CH with PLPAO (CH+PLPAO) models. Hemodynamic measurements also show no change in the pulmonary vascular resistance with captopril treatment in both CH and CH+PLPAO.

A novel mouse model of high flow-induced pulmonary hypertension-surgically induced by right pulmonary artery ligation.

PubMed

Zhang, Anchen; Wang, Hongfei; Wang, Shengwei; Huang, Xiaofan; Ye, Ping; Du, Xinling; Xia, Jiahong

2017-02-01

This study sought to establish a new model of high-flow pulmonary hypertension (PH) in mice. This model may be useful for studies seeking to reduce the pulmonary vascular resistance and delay the development of PH caused by congenital heart disease. The right pulmonary artery was ligated via a right posterolateral thoracotomy. Pulmonary hemodynamics was evaluated by right heart catheterization immediately after ligation and at 2, 4, 8, and 12 wk postoperatively. The right ventricle (RV) and the left ventricle (LV) with septum (S) were weighed to calculate the RV/(LV + S) ratio as an index of right ventricular hypertrophy. Morphologic changes in the left lungs were analyzed, and percentages of muscularized pulmonary vessels were assessed by hematoxylin and eosin, elastica van Gieson and alpha-smooth muscle actin staining. All the study data were compared with data from a model of PH generated by hypoxic stimulation. A pulmonary hypertensive state was successfully induced by 2 wk after surgery. However, the morphologic analysis demonstrated that pulmonary vascular muscularization, as evaluated using right ventricular systolic pressure and RV/(LV + S), was not significantly increased until 4 wk postoperatively. When mice from the new model and the hypoxic model were compared, no significant differences were observed in any of the evaluated indices. High-flow PH can be induced within 4 wk after ligation of the right pulmonary artery, which is easily performed in mice. Such mice can be used as a model of high-flow PH. Copyright © 2016 Elsevier Inc. All rights reserved.

Inhaled nitric oxide, oxygen, and alkalosis: dose-response interactions in a lamb model of pulmonary hypertension.

PubMed

Heidersbach, R S; Johengen, M J; Bekker, J M; Fineman, J R

1999-07-01

Inhaled nitric oxide (NO) is currently used as an adjuvant therapy for a variety of pulmonary hypertensive disorders. In both animal and human studies, inhaled NO induces selective, dose-dependent pulmonary vasodilation. However, its potential interactions with other simultaneously used pulmonary vasodilator therapies have not been studied. Therefore, the objective of this study was to determine the potential dose-response interactions of inhaled NO, oxygen, and alkalosis therapies. Fourteen newborn lambs (age 1-6 days) were instrumented to measure vascular pressures and left pulmonary artery blood flow. After recovery, the lambs were sedated and mechanically ventilated. During steady-state pulmonary hypertension induced by U46619 (a thromboxane A2 mimic), the lambs were exposed to the following conditions: Protocol A, inhaled NO (0, 5, 40, and 80 ppm) and inspired oxygen concentrations (FiO2) of 0.21, 0.50, and 1.00; and Protocol B, inhaled NO (0, 5, 40, and 80 ppm) and arterial pH levels of 7.30, 7.40, 7.50, and 7.60. Each condition (in randomly chosen order) was maintained for 10 min, and all variables were allowed to return to baseline between conditions. Inhaled NO, oxygen, and alkalosis produced dose-dependent decreases in mean pulmonary arterial pressures (P < 0.05). Systemic arterial pressure remained unchanged. At 5 ppm of inhaled NO, alkalosis and oxygen induced further dose-dependent decreases in mean pulmonary arterial pressures (P < 0.05). At inhaled NO doses > 5 ppm, alkalosis induced further dose-independent decreases in mean pulmonary arterial pressure, while oxygen did not. We conclude that in this animal model, oxygen, alkalosis, and inhaled NO induced selective, dose-dependent pulmonary vasodilation. However, when combined, a systemic arterial pH > 7.40 augmented inhaled NO-induced pulmonary vasodilation, while an FiO2 > 0.5 did not. Therefore, weaning high FiO2 during inhaled NO therapy should be considered, since it may not diminish the pulmonary vasodilating effects. Further studies are warranted to guide the clinical weaning strategies of these pulmonary vasodilator therapies.

Novel putative pharmacological therapies to protect the right ventricle in pulmonary hypertension: a review of current literature

PubMed Central

Schulz, Rainer; Sliwa, Karen; Schermuly, Ralph Theo; Lecour, Sandrine

2017-01-01

Pulmonary hypertension (PH) is defined by elevated mean pulmonary artery pressure following the pathological remodelling of small pulmonary arteries. An increase in right ventricular (RV) afterload results in RV hypertrophy and RV failure. The pathophysiology of PH, and RV remodelling in particular, is not well understood, thus explaining, at least in part, why current PH therapies have a limited effect. Existing therapies mostly target the pulmonary circulation. Because the remodelled RV fails to support normal cardiac function, patients eventually succumb from RV failure. Developing novel therapies that directly target the function of the RV may therefore benefit patients with PH. In the past decade, several promising studies have investigated novel cardioprotective strategies in experimental models of PH. This review aims to comprehensively discuss and highlight these novel experimental approaches to confer, in the long‐term, greater health benefit in patients with PH. PMID:28099680

Venous Fragment Embolism to the Pulmonary Artery: A Rare Occurrence - Case Report and Literature Review of Venous Fragment Embolization to the Pulmonary Artery

DTIC Science & Technology

2009-09-01

identified the high density (3000 Hounsfield Units ) intravascular pulmonary fragment in the same location, right lower lobe pulmonary artery, measuring...debridement and a four- compartment fasciotomy due to increasing compartment pressures. Anticoagulation was continued, 4 units of blood Report...NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Uniformed

Ultrasonic Estimation of Mechanical Properties of Pulmonary Arterial Wall Under Normoxic and Hypoxic Conditions

NASA Astrophysics Data System (ADS)

Waters, Kendall R.; Mukdadi, Osama M.

2005-04-01

Secondary pediatric pulmonary hypertension is a disease that could benefit from improved ultrasonic diagnostic techniques. We perform high-frequency in vitro ultrasound measurements (25 MHz to 100 MHz) on fresh and fixed pulmonary arterial walls excised from normoxic and hypoxic Long-Evans rat models. Estimates of the elastic stiffness coefficients are determined from measurements of the speed of sound. Preliminary results indicate that hypoxia leads to up to increase of 20 % in stiffening of the pulmonary arterial wall.

The pulmonary circulation of some domestic animals at high altitude

NASA Astrophysics Data System (ADS)

Anand, I.; Heath, D.; Williams, D.; Deen, M.; Ferrari, R.; Bergel, D.; Harris, P.

1988-03-01

Pulmonary haemodynamics and the histology of the pulmonary vasculature have been studied at high altitude in the yak, in interbreeds between yaks and cattle, and in domestic goats and sheep indigenous to high altitudes together with crosses between them and low-altitude strains. Cattle at high altitude had a higher pulmonary arterial pressure than cattle at low altitude. The yak and two interbreeds with cattle (dzos and stols) had a low pulmonary arterial pressure compared with cattle, while the medial thickness of the small pulmonary arteries was less than would be expected in cattle, suggesting that the yak has a low capacity for hypoxic pulmonary vasoconstriction and that this characteristic is transmitted genetically. Goats and sheep showed haemodynamic evidence of a limited response of the pulmonary circulation to high altitude, but no evidence that the high altitude breeds had lost this response. There were no measurable differences in the thickness of the media of the small pulmonary arteries between high- and low-altitude breeds of goats and sheep. All these species showed prominent intimal protrusions of muscle into the pulmonary veins but no specific effect of high altitude in this respect.

Value of two-dimensional echocardiography in the identification of pulmonary hypertension in chronic obstructive lung disease.

PubMed

Bertoli, L; Mantero, A; Alpago, R; Graziina, A; Tamponi, M; Pezzano, A

1989-01-01

Thirty-three patients suffering from chronic obstructive lung disease (COLD) were submitted to right heart two-dimensional echocardiographic (2D-ECHO) and hemodynamic study. By the subcostal approach, the right ventricle outflow tract including the pulmonary vessels was visualized in 85% of the patients. Most parameters measured on the right ventricle and pulmonary vessels were significantly higher than those recorded in the healthy control group. Very significant correlations were observed between the mean pulmonary artery pressure (PAP) and the following 2D-ECHO parameters: diameter of the pulmonary artery at valve level (r = 0.62; p less than 0.001); supravalvular diameter of the pulmonary artery (r = 0.44; p less than 0.03); diameter of the left branch of the pulmonary artery (r = 0.48; p less than 0.05); diameter of the right branch of the pulmonary artery (r = 0.39; p less than 0.05), and between the PAP and PaO2 (r = -0.66; p less than 0.001). Furthermore, the sensitivity, specificity, and accuracy of 2D-ECHO measurements were calculated to assess the presence of pulmonary hypertension. Overall sensitivity was 65%, specificity 75%, and accuracy 67%. However, by combining the value of PaO2 with that of the pulmonary valve by means of the multiple regression analysis, sensitivity increased to 84% in identifying pulmonary hypertension. Such data demonstrate that the 2D-ECHO study of the right heart in COLD patients has to carefully measure the dimensions of the pulmonary valve and the great pulmonary vessels, as their modification are mainly linked with the presence of pulmonary hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

A novel multiscale topo-morphometric approach for separating arteries and veins via pulmonary CT imaging

NASA Astrophysics Data System (ADS)

Saha, Punam K.; Gao, Zhiyun; Alford, Sara; Sonka, Milan; Hoffman, Eric

2009-02-01

Distinguishing arterial and venous trees in pulmonary multiple-detector X-ray computed tomography (MDCT) images (contrast-enhanced or unenhanced) is a critical first step in the quantification of vascular geometry for purposes of determining, for instance, pulmonary hypertension, using vascular dimensions as a comparator for assessment of airway size, detection of pulmonary emboli and more. Here, a novel method is reported for separating arteries and veins in MDCT pulmonary images. Arteries and veins are modeled as two iso-intensity objects closely entwined with each other at different locations at various scales. The method starts with two sets of seeds -- one for arteries and another for veins. Initialized with seeds, arteries and veins grow iteratively while maintaining their spatial separation and eventually forming two disjoint objects at convergence. The method combines fuzzy distance transform, a morphologic feature, with a topologic connectivity property to iteratively separate finer and finer details starting at a large scale and progressing towards smaller scales. The method has been validated in mathematically generated tubular objects with different levels of fuzziness, scale and noise. Also, it has been successfully applied to clinical CT pulmonary data. The accuracy of the method has been quantitatively evaluated by comparing its results with manual outlining. For arteries, the method has yielded correctness of 81.7% at the cost of 6.7% false positives and 11.6% false negatives. Our method is very promising for automated separation of arteries and veins in MDCT pulmonary images even when there is no mark of intensity variation at conjoining locations.

Pulmonary artery closure in combination with patch technique for treating congenital heart disease combined with large patent ductus arteriosus: A clinical study of 9 cases

PubMed Central

Wen, Bing; Yang, Junya; Liu, Huiruo; Jiao, Zhouyang; Zhao, Wenzeng

2016-01-01

Objective: To document clinical experience of treating congenital heart disease combined with large patent ductus arteriosus with pulmonary artery closure in combination with patch technique. Methods: Thirty-six patients (8 males and 28 females) who suffered from congenital heart disease and underwent hybrid surgery in the First Affiliated Hospital of Zhengzhou University from October 2010 to February 2014 were selected for this study. They aged 14 to 39 years and weighed 32.20 to 61.50 kg. Diameter of arterial duct was between 10 mm and 13 mm; 28 cases were tube type, 4 cases were funnel type and four cases were window type. All patients had moderate or severe pulmonary arterial hypertension; besides, there were 28 cases of ventricular septal defect, 16 cases of atrial septal defect, eight cases of aortic insufficiency, four cases of mitral stenosis and insufficiency and four cases of infectious endocarditis. Cardz Pulmonary Bypass (CPB) was established after chest was opened along the middle line. With the help of Transesophageal echocardiography, large patent ductus arteriosus was blocked off through pulmonary artery. Pulmonary artery was cut apart after blocking of heart. Large patent ductus arteriosus on the side of pulmonary artery was strengthened with autologous pericardial patch. Results: Of 36 patients, 32 patients had patent ductus arteriosus closure device and four patients had atrial septal defect closure device. Pulmonary arteries of 36 cases were all successfully closed. Systolic pressure declined after closure ((54.86±19.23) mmHg vs (96.05±23.07) mmHg, p<0.05); average pulmonary arterial pressure also declined after closure ((39.15±14.83) mmHg vs (72.88±15.76) mmHg, p<0.05). The patients were followed up for one to fifty one months (average 11.5 months). Compared to before surgery, left atrial diameter, left ventricular diameter and pulmonary artery diameter all narrowed after surgery. Besides, clinical symptoms were relieved and cardiac function of the patients also improved. Conclusion: Hybrid surgery is feasible and safe in treating patients with large patent ductus arteriosus and congenital heart disease, which decreases surgical problems, shortens surgical time and lowers the incidence of complications. PMID:27375685

Pulmonary artery closure in combination with patch technique for treating congenital heart disease combined with large patent ductus arteriosus: A clinical study of 9 cases.

PubMed

Wen, Bing; Yang, Junya; Liu, Huiruo; Jiao, Zhouyang; Zhao, Wenzeng

2016-01-01

To document clinical experience of treating congenital heart disease combined with large patent ductus arteriosus with pulmonary artery closure in combination with patch technique. Thirty-six patients (8 males and 28 females) who suffered from congenital heart disease and underwent hybrid surgery in the First Affiliated Hospital of Zhengzhou University from October 2010 to February 2014 were selected for this study. They aged 14 to 39 years and weighed 32.20 to 61.50 kg. Diameter of arterial duct was between 10 mm and 13 mm; 28 cases were tube type, 4 cases were funnel type and four cases were window type. All patients had moderate or severe pulmonary arterial hypertension; besides, there were 28 cases of ventricular septal defect, 16 cases of atrial septal defect, eight cases of aortic insufficiency, four cases of mitral stenosis and insufficiency and four cases of infectious endocarditis. Cardz Pulmonary Bypass (CPB) was established after chest was opened along the middle line. With the help of Transesophageal echocardiography, large patent ductus arteriosus was blocked off through pulmonary artery. Pulmonary artery was cut apart after blocking of heart. Large patent ductus arteriosus on the side of pulmonary artery was strengthened with autologous pericardial patch. Of 36 patients, 32 patients had patent ductus arteriosus closure device and four patients had atrial septal defect closure device. Pulmonary arteries of 36 cases were all successfully closed. Systolic pressure declined after closure ((54.86±19.23) mmHg vs (96.05±23.07) mmHg, p<0.05); average pulmonary arterial pressure also declined after closure ((39.15±14.83) mmHg vs (72.88±15.76) mmHg, p<0.05). The patients were followed up for one to fifty one months (average 11.5 months). Compared to before surgery, left atrial diameter, left ventricular diameter and pulmonary artery diameter all narrowed after surgery. Besides, clinical symptoms were relieved and cardiac function of the patients also improved. Hybrid surgery is feasible and safe in treating patients with large patent ductus arteriosus and congenital heart disease, which decreases surgical problems, shortens surgical time and lowers the incidence of complications.

Total cavo-pulmonary connection without foreign material for asplenic heart associated with partial anomalous pulmonary venous connection.

PubMed

Agematsu, Kouta; Naito, Yuji; Aoki, Mitsuru; Fujiwara, Tadashi

2008-04-01

The presented case was a 3-year-old boy diagnosed with asplenia (SLL), double outlet right ventricle, pulmonary stenosis, atrioventricular septal defect, hypoplastic left ventricle and partial anomalous pulmonary venous connection to the superior vena cava. Partial anomalous pulmonary venous connection was repaired by translocation of pulmonary artery to avoid pulmonary venous obstruction when Glenn anastomosis was performed. Total cavo-pulmonary connection was established by re-routing the inferior vena cava to pulmonary artery using the atrial septal remnant and the left atrium free wall flap.

Mechanical support of total cavopulmonary connection with an axial flow pump.

PubMed

Riemer, R Kirk; Amir, Gabriel; Reichenbach, Steven H; Reinhartz, Olaf

2005-08-01

Even under optimal circumstances, total cavopulmonary connection is associated with a continuous late risk of death. Hemodynamics are distinctly abnormal, with increased systemic venous pressures and frequent low cardiac output. Our study uses a sheep model of total cavopulmonary connection to test the response to axial flow pump (Thoratec HeartMate II; Thoratec Corporation (Pleasanton, Calif)) support of total cavopulmonary connection, which might be suitable to treat patients with failing Fontan circulation. Eight sheep (42-48 kg) were studied. After pilot studies in 3 animals, 5 underwent both pump-supported and nonsupported total cavopulmonary connection in alternating sequence for up to 2 hours. This was achieved with a 12-mm polytetrafluoroethylene graft from the (distally ligated) superior vena cava to the main pulmonary artery and a cannula placed in the inferior vena cava with an attached 16-mm Dacron graft to the main pulmonary artery. Pressures (arterial, inferior vena cava, left atrium, and pulmonary artery) and flows (ascending aorta and inferior vena cava) were recorded over 1 hour both with unsupported total cavopulmonary connection and after placing an axial flow pump (Thoratec HeartMate II) between the inferior vena caval inflow cannula and the main pulmonary artery. Under nonsupported total cavopulmonary connection circulation, inferior vena caval and aortic blood flow decreased by nearly 50%. Inferior vena caval pressure nearly doubled, whereas arterial pressure decreased by one third. Pulmonary artery pressure became nonpulsatile; however, mean pulmonary artery pressure and left atrial pressure did not change significantly. With pump-supported Fontan circulation, cardiac output, inferior vena caval flow, and arterial pressure returned to baseline. Inferior vena caval pressure decreased to below baseline levels. Mean pulmonary artery pressure and left atrial pressure again remained unchanged. Axial flow pump support from the inferior vena cava to the pulmonary artery can prevent the substantial decrease of aortic flow and pressure associated with total cavopulmonary connection and can reverse its poor hemodynamics. This is a simple model that can be used to further evaluate the potential of mechanical support as a treatment option in failing Fontan circulation.

Rapamycin nanoparticles localize in diseased lung vasculature and prevent pulmonary arterial hypertension.

PubMed

Segura-Ibarra, Victor; Amione-Guerra, Javier; Cruz-Solbes, Ana S; Cara, Francisca E; Iruegas-Nunez, David A; Wu, Suhong; Youker, Keith A; Bhimaraj, Arvind; Torre-Amione, Guillermo; Ferrari, Mauro; Karmouty-Quintana, Harry; Guha, Ashrith; Blanco, Elvin

2017-05-30

Vascular remodeling resulting from pulmonary arterial hypertension (PAH) leads to endothelial fenestrations. This feature can be exploited by nanoparticles (NP), allowing them to extravasate from circulation and accumulate in remodeled pulmonary vessels. Hyperactivation of the mTOR pathway in PAH drives pulmonary arterial smooth muscle cell proliferation. We hypothesized that rapamycin (RAP)-loaded NPs, an mTOR inhibitor, would accumulate in diseased lungs, selectively targeting vascular mTOR and preventing PAH progression. RAP poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL) NPs were fabricated. NP accumulation and efficacy were examined in a rat monocrotaline model of PAH. Following intravenous (IV) administration, NP accumulation in diseased lungs was verified via LC/MS analysis and confocal imaging. Pulmonary arteriole thickness, right ventricular systolic pressures, and ventricular remodeling were determined to assess the therapeutic potential of RAP NPs. Monocrotaline-exposed rats showed increased NP accumulation within lungs compared to healthy controls, with NPs present to a high extent within pulmonary perivascular regions. RAP, in both free and NP form, attenuated PAH development, with histological analysis revealing minimal changes in pulmonary arteriole thickness and no ventricular remodeling. Importantly, NP-treated rats showed reduced systemic side effects compared to free RAP. This study demonstrates the potential for nanoparticles to significantly impact PAH through site-specific delivery of therapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

Anomalous left coronary artery from the pulmonary artery

MedlinePlus

... begins from the pulmonary artery instead of the aorta. ALCAPA is present at birth (congenital) . Causes ALCAPA ... the normal heart, the LCA originates from the aorta. It supplies oxygen-rich blood to the heart ...

Hemodynamic Assessment of Compliance of Pre-Stressed Pulmonary Valve-Vasculature in Patient Specific Geometry Using an Inverse Algorithm

NASA Astrophysics Data System (ADS)

Hebbar, Ullhas; Paul, Anup; Banerjee, Rupak

2016-11-01

Image based modeling is finding increasing relevance in assisting diagnosis of Pulmonary Valve-Vasculature Dysfunction (PVD) in congenital heart disease patients. This research presents compliant artery - blood interaction in a patient specific Pulmonary Artery (PA) model. This is an improvement over our previous numerical studies which assumed rigid walled arteries. The impedance of the arteries and the energy transfer from the Right Ventricle (RV) to PA is governed by compliance, which in turn is influenced by the level of pre-stress in the arteries. In order to evaluate the pre-stress, an inverse algorithm was developed using an in-house script written in MATLAB and Python, and implemented using the Finite Element Method (FEM). This analysis used a patient specific material model developed by our group, in conjunction with measured pressure (invasive) and velocity (non-invasive) values. The analysis was performed on an FEM solver, and preliminary results indicated that the Main PA (MPA) exhibited higher compliance as well as increased hysteresis over the cardiac cycle when compared with the Left PA (LPA). The computed compliance values for the MPA and LPA were 14% and 34% lesser than the corresponding measured values. Further, the computed pressure drop and flow waveforms were in close agreement with the measured values. In conclusion, compliant artery - blood interaction models of patient specific geometries can play an important role in hemodynamics based diagnosis of PVD.

Tyrosine kinase inhibitors in pulmonary arterial hypertension: a double-edge sword?

PubMed

Godinas, Laurent; Guignabert, Christophe; Seferian, Andrei; Perros, Frederic; Bergot, Emmanuel; Sibille, Yves; Humbert, Marc; Montani, David

2013-10-01

New treatments for pulmonary arterial hypertension (PAH) are a crucial need. The increased proliferation, migration, and survival of pulmonary vascular cells within the pulmonary artery wall in PAH have allowed successful transposition of pathophysiological elements from oncologic researches. Next steps will require translation of these biological advances in PAH therapeutic arsenal and guidelines. This review synthesizes recent data concerning the role of receptor tyrosine kinases and their inhibitors in PAH, with implications in animal models and humans. Results of clinical trials are now accumulating to establish beneficial role of tyrosine kinase inhibitors (TKIs) in PAH and further findings are expected in the near future. Beside this curative approach, evidences of a possible TKI-induced cardiotoxicity are emerging. These safety issues raise concern about a potential amplified harmful effect in PAH, a pathology characterized by an underlying cardiac dysfunction. In addition, analyses of PAH registries shed light on a selective pulmonary vascular toxicity triggered by TKIs, especially dasatinib. These possible dual effects of the TKIs in PAH need to be taken in account for future pharmacological development of this therapeutic class in PAH. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Transesophageal Echocardiographic Assessment of Pulmonary Artery-to-Ascending Aorta Ratio for the Detection of Pulmonary Hypertension in Cardiac Surgical Patients.

PubMed

Narendra Kumar, Karthik; Singh, Naveen G; P S, Nagaraja; Patil, Thimmangouda A; N, Manjunath

2017-10-01

The objective of the study was to investigate if the main pulmonary artery (mPA)-to-ascending aorta (AscAo), (mPA:AscAo) ratio could serve as a screening tool in identifying pulmonary artery hypertension (PAH). A prospective observational study. Tertiary care center, university hospital. Fifty-four adult patients undergoing off-pump coronary artery bypass grafting surgery (OPCAB). mPA and AscAo transverse diameters were measured by transesophageal echocardiography (TEE) and the mean pulmonary arterial pressures (mPAP) were recorded simultaneously using a pulmonary artery catheter. mPA:AscAo ratio demonstrated significant linear correlation with mPAP measured by pulmonary artery catheterization (ie, r = 0.61, confidence interval [CI] = 0.5352-0.6736, p < 0.0001). Receiver operating characteristic curves were performed to evaluate sensitivity and specificity of mPA:AscAo ratio ≥1 for diagnosing PAH (mPAP ≥25 mmHg). Area under the curve for mPA:AscAo ratio was 0.91 (95% CI, 0.869-0.936, p < 0.0001), with a sensitivity of 84.27%, specificity of 83.92%, positive-predictive value of 87.6% and negative-predictive value of 81.1% for a mPAP ≥25 mmHg. The ratio of mPA:AscAo is a simple, reliable, and reproducible method that can be obtained through TEE, which guides the clinician to screen patients with PAH. Copyright © 2017 Elsevier Inc. All rights reserved.

Percutaneous Pulmonary Valve Placement

PubMed Central

Prieto, Lourdes R.

2015-01-01

Patients with congenital heart disease and pulmonary valve disease need multiple procedures over their lifetimes to replace their pulmonary valves. Chronic pulmonary stenosis, regurgitation, or both have untoward effects on ventricular function and on the clinical status of these patients. To date, all right ventricle–pulmonary artery conduits have had relatively short lifespans. Percutaneous pulmonary valve implantation, although relatively new, will probably reduce the number of operative procedures that these patients will have to undergo over a lifetime. Refinement and further development of this procedure holds promise for the extension of this technology to other patient populations. PMID:26175629

[Pulmonary hypertensive crisis in children with idiopathic pulmonary arterial hypertension undergoing cardiac catheterization: the risk factors and clinical aspects].

PubMed

Zhang, C; Zhu, Y; Li, Q Q; Gu, H

2018-06-02

Objective: To investigate the risk factors, clinical features, treatments, and prevention of pulmonary hypertensive crisis (PHC) in children with idiopathic pulmonary arterial hypertension (IPAH) undergoing cardiac catheterization. Methods: This retrospective study included 67 children who were diagnosed with IPAH and underwent cardiac catheterization between April 2009 and June 2017 in Beijing Anzhen Hospital. The medical histories, clinical manifestations, treatments, and outcomes were characterized. Statistical analyses were performed using t test, χ(2) test and a multiple Logistic regression analysis. Results: During cardiac catheterization, five children developed PHC who presented with markedly elevated pulmonary artery pressure and central venous pressure, decline in systemic arterial pressure and oxygen saturation. Heart rate decreased in 4 cases and increased in the remaining one. After the treatments including cardiopulmonary resuscitation, pulmonary vasodilator therapy, improving cardiac output and blood pressure, and correction of acidosis, 4 of the 5 cases recovered, while 1 died of severe right heart failure with irreversible PHC 3 days after operation. Potential PHC was considered in 7 other patients, whose pulmonary artery pressure increased and exceeded systemic arterial pressure, oxygen saturation decreased, and central venous pressure and vital signs were relatively stable. Univariate analysis showed that the risk factors of PHC in children with IPAH undergoing cardiac catheterization were younger age ( t= 3.160, P= 0.004), low weight ( t= 4.004, P< 0.001), general anesthesia (χ(2)=4.970, P= 0.026), history of syncope (χ(2)=4.948, P= 0.026), and WHO cardiac functional class Ⅲ or Ⅳ (χ(2)=19.013, P< 0.001). Multivariate Logistic regression analysis revealed that worse WHO cardiac functional class ( Wald =13.128, P< 0.001, OR= 15.076, 95% CI : 3.475-65.418) was the independent risk factor of PHC. Conclusions: PHC is a severe and extremely dangerous complication in children with IPAH during cardiac catheterization. WHO cardiac functional class may be associated with PHC. Integrated treatment is required for these patients. Reducing risk factors, early identification, and active treatment may help to prevent the occurrence and progression of PHC.

Late Diagnosed Left Coronary to the Pulmonary Artery Large Fistulae: An Interesting and Incidental Cath Lab Finding

PubMed Central

de Melo, Pedro H. M. Craveiro; Abreu-Silva, Érlon O.; Coura, Fernando Barbiero; Rios, Gleyson Moraes; Potério, Daniel Izzet

2016-01-01

Coronary artery anomalies are congenital changes in their origin, course, and/or structure. Most of them are discovered as incidental findings during coronary angiographic studies or at autopsies. A coronary artery fistulae involve a communication between a coronary artery and a chamber of the heart or any segment of the systemic or pulmonary circulation. We present herein the case of a 67-year-old man with a recent history of exertional angina and dyspnea to usual daily activities whose coronary angiogram revealed an interesting and incidental coronary-pulmonary artery large fistulae. PMID:28053791

Late Diagnosed Left Coronary to the Pulmonary Artery Large Fistulae: An Interesting and Incidental Cath Lab Finding.

PubMed

Oliveira, Marcos Danillo P; de Melo, Pedro H M Craveiro; Abreu-Silva, Érlon O; Coura, Fernando Barbiero; Rios, Gleyson Moraes; Potério, Daniel Izzet

2016-01-01

Coronary artery anomalies are congenital changes in their origin, course, and/or structure. Most of them are discovered as incidental findings during coronary angiographic studies or at autopsies. A coronary artery fistulae involve a communication between a coronary artery and a chamber of the heart or any segment of the systemic or pulmonary circulation. We present herein the case of a 67-year-old man with a recent history of exertional angina and dyspnea to usual daily activities whose coronary angiogram revealed an interesting and incidental coronary-pulmonary artery large fistulae.

Abolished ventilation and perfusion of lung caused by blood clot in the left main bronchus: auto-downregulation of pulmonary arterial blood supply.

PubMed

Afzelius, P; Bergmann, A; Henriksen, J H

2015-09-15

It is generally assumed that the lungs possess arterial autoregulation associated with bronchial obstruction. A patient with pneumonia and congestive heart failure unexpectedly developed frequent haemoptysis. High-resolution CT and diagnostic CT were performed as well as ventilation/perfusion (V/Q) scintigraphy with single-photon emission CT (SPECT)/CT. V/Q SPECT/CT demonstrated abolished ventilation due to obstruction of the left main bronchus and markedly reduced perfusion of the entire left lung, a condition that was completely reversed after removal of a blood clot. We present the first pictorially documented case of hypoxia-induced pulmonary vasoconstriction and flow shift in a main pulmonary artery due to a complete intrinsic obstruction of the ipsilateral main bronchus. The condition is reversible, contingent on being relieved within a few days. 2015 BMJ Publishing Group Ltd.

Interventional and surgical therapeutic strategies for pulmonary arterial hypertension: Beyond palliative treatments.

PubMed

Sandoval, Julio; Gomez-Arroyo, Jose; Gaspar, Jorge; Pulido-Zamudio, Tomas

2015-10-01

Despite significant advances in pharmacological treatments, pulmonary arterial hypertension remains an incurable disease with an unreasonably high morbidity and mortality. Although specific pharmacotherapies have shifted the survival curves of patients and improved exercise endurance as well as quality of life, it is also true that these pharmacological interventions are not always accessible (particularly in developing countries) and, perhaps most importantly, not all patients respond similarly to these drugs. Furthermore, many patients will continue to deteriorate and will eventually require an additional, non-pharmacological, intervention. In this review we analyze the role of atrial septostomy and Potts anastomosis in the management of patients with pulmonary arterial hypertension, we summarize the current worldwide clinical experience (case reports and case series), and discuss why these interventional/surgical strategies might have a therapeutic role beyond that of a "bridge" to transplantation. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Neonatal pulmonary arterial hypertension and Noonan syndrome: two fatal cases with a specific RAF1 mutation.

PubMed

Hopper, Rachel K; Feinstein, Jeffrey A; Manning, Melanie A; Benitz, William; Hudgins, Louanne

2015-04-01

Mutations in RAF1 are associated with Noonan syndrome and hypertrophic cardiomyopathy. We present two infants with Noonan syndrome and an identical RAF1 mutation, p.Ser257Leu (c.770C>T), who developed severe pulmonary arterial hypertension (PAH) that proved to be fatal. The RAF1 gene encodes Raf-1 kinase, part of the Ras/mitogen-activated kinase (MAPK) signaling pathway, which has been linked to the development of PAH. This specific mutation has been associated with dephosphorylation of a critical serine residue and constitutive activation of the Raf-1 kinase. These two cases suggest that abnormal activation of the Ras/MAPK pathway may play a significant role in the development of pulmonary vascular disease in the subset of patients with Noonan syndrome and a specific RAF1 mutation. © 2015 Wiley Periodicals, Inc.

Acute effects of the combination of sildenafil and inhaled treprostinil on haemodynamics and gas exchange in pulmonary hypertension.

PubMed

Voswinckel, Robert; Reichenberger, Frank; Enke, Beate; Kreckel, Andre; Krick, Stefanie; Gall, Henning; Schermuly, Ralph Theo; Grimminger, Friedrich; Rubin, Lewis J; Olschewski, Horst; Seeger, Werner; Ghofrani, Hossein A

2008-10-01

Inhaled treprostinil was recently developed for the treatment of pulmonary arterial hypertension (PAH). We investigated the safety and acute haemodynamic effects of the combination oral sildenafil and inhaled treprostinil in an open label study in patients with precapillary pulmonary hypertension. Inhaled nitric oxide (20ppm; n=50), sildenafil (50mg; n=50) and inhaled treprostinil (15microg; n=25 or 30microg; n=25) were applied in subsequent order during right heart catheter investigation to consecutive patients with pulmonary arterial hypertension (PAH; n=28), non-operable chronic thromboembolic pulmonary hypertension (CTEPH; n=17) and pulmonary fibrosis associated pulmonary hypertension (n=5). Inhaled nitric oxide reduced pulmonary vascular resistance (PVR) to 87.3+/-5.1% of baseline values, reduced mean pulmonary arterial pressure (PAP) to 89.7+/-3.5% and increased cardiac output (CO) to 102.4+/-2.9%. Sildenafil reduced PVR to 80.1+/-5.0%, mPAP to 86.5+/-2.9% and increased CO to 103.8+/-3.2%. Treprostinil, inhaled 1h after sildenafil, reduced PVR to 66.3+/-3.8%, mPAP to 77.8+/-3.3%, and increased CO to 107.1+/-3.3% (mean+/-95% confidence interval). Subgroup analysis showed similar acute haemodynamic effects in PAH and CTEPH patients. Ventilation/perfusion distribution measurement in six patients with pre-existing gas exchange limitations was not changed by sildenafil and treprostinil. Relevant side effects were not observed. The combination of sildenafil and inhaled treprostinil was well tolerated and induced additive, pulmonary selective vasodilatation in pulmonary hypertension patients. This could be of relevance also for long-term treatment of PAH and CTEPH patients.

[Impact of multi-layer spiral CT angiography of bronchial artery and pulmonary artery in assessment of the main blood supply to the primary lung cancer].

PubMed

Xiao, Xiang-sheng; Yu, Hong; Li, Hui-min; Liu, Shi-yuan; Li, Cheng-zhou; Liu, Jing

2006-04-01

To investigate the blood supply of primary lung cancer (PLC) using CT angiography for bronchial artery (BA) and pulmonary artery (PA). Thin-section enhanced multi-layer spiral CT (MSCT) were carried out in 147 primary lung cancer patients and 46 healthy subjects as control. Three-dimensional images of bronchial artery and pulmonary artery were obtained using volume render (VR) and multi-planar reconstruction (MPR) or maximum intensity projection (MIP) at the workstation, and their morphological findings and relationship with the mass were assessed. 136 primary lung cancer patients and 32 healthy controls were evaluated for at least one bronchial artery displayed clearly in VR. The detective rate of the bronchial artery was 92.5% and 69.6%, respectively. The bronchial artery caliber and the total section area of lesion side in lung cancer patients were significantly larger than that on the contralateral side and that of the control (P < 0.05). Bronchial artery on the lesion side in lung cancer was dilated and tortuous, directly penetrating into the mass with reticularly anastomosed branches. In the PLC patients, all PA were shown clearly with normal morphological image though crossing over the masses in 54 patients; In 25 PLC patients, the PA being essentially intact, was pushed around and surrounded the mass, giving the "hold ball" sign; In 40 other PLC patients, PA being also intact, the mass surrounded and buried the PA from the outside, crushing the PA flat resulting in an eccentric or centrifugal shrinkage, forming the "dead branch" sign; In the rest 28 patients, the PA was surrounded and even compressed, forming the "residual root" sign. Primary lung cancer patient shows dilated bronchial arteries and increased bronchial artery blood flow, whereas pulmonary arteries just pass through the mass or are compressed by the mass. It is further demonstrated that the bronchial artery, instead of the pulmonary artery, is the main vessel of blood supply to the primary lung cancer as shown by MSCT angiography of bronchial artery and pulmonary artery.

Pulmonary artery dissection in eight dogs with patent ductus arteriosus.

PubMed

Scansen, Brian A; Simpson, Elaine M; López-Alvarez, Jordi; Thomas, William P; Bright, Janice M; Eason, Bryan D; Rush, John E; Dukes-McEwan, Joanna; Green, Henry W; Cunningham, Suzanne M; Visser, Lance C; Kent, Agnieszka M; Schober, Karsten E

2015-06-01

To describe a series of dogs with pulmonary artery dissection and patent ductus arteriosus (PDA). Eight dogs. Retrospective case series. Pulmonary artery dissection was diagnosed in 8 dogs, 3 were Weimaraners. Four dogs presented in left-sided congestive heart failure, 4 presented for murmur evaluation and without clinical signs, and 1 presented in right-sided congestive heart failure. In 7 dogs the dissection was first documented concurrent with a diagnosis of uncorrected PDA. In the other dog, with pulmonary valve stenosis and PDA, the dissection was observed on autopsy examination 17 months after balloon pulmonary valvuloplasty and ductal closure. Median age at presentation for the 7 dogs with antemortem diagnosis of pulmonary artery dissection was 3.5 years (range, 1.5-4 years). Three dogs had the PDA surgically ligated, 2 dogs did not undergo PDA closure, 1 dog failed transcatheter occlusion of the PDA with subsequent surgical ligation, 1 dog underwent successful transcatheter device occlusion of the PDA, and 1 dog had the PDA closed by transcatheter coil delivery 17 months prior to the diagnosis of pulmonary artery dissection. The 2 dogs that did not have the PDA closed died 1 and 3 years after diagnosis due to heart failure. Pulmonary artery dissection is a potential complication of PDA in dogs, the Weimaraner breed may be at increased risk, presentation is often in mature dogs, and closure of the PDA can be performed and appears to improve outcome. Copyright © 2014 Elsevier B.V. All rights reserved.

Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension

PubMed Central

Aghamohammadzadeh, Reza; Zhang, Ying-Yi; Stephens, Thomas E.; Arons, Elena; Zaman, Paula; Polach, Kevin J.; Matar, Majed; Yung, Lai-Ming; Yu, Paul B.; Bowman, Frederick P.; Opotowsky, Alexander R.; Waxman, Aaron B.; Loscalzo, Joseph; Leopold, Jane A.; Maron, Bradley A.

2016-01-01

Activation of the mammalian target of rapamycin complex 1 (mTORC1) subunit Raptor induces cell growth and is a downstream target of Akt. Elevated levels of aldosterone activate Akt, and, in pulmonary arterial hypertension (PAH), correlate with pulmonary arteriole thickening, which suggests that mTORC1 regulation by aldosterone may mediate adverse pulmonary vascular remodeling. We hypothesized that aldosterone-Raptor signaling induces abnormal pulmonary artery smooth muscle cell (PASMC) survival patterns to promote PAH. Remodeled pulmonary arterioles from SU-5416/hypoxia-PAH rats and monocrotaline-PAH rats with hyperaldosteronism expressed increased levels of the Raptor target, p70S6K, which provided a basis for investigating aldosterone-Raptor signaling in human PASMCs. Aldosterone (10−9 to 10−7 M) increased Akt/mTOR/Raptor to activate p70S6K and increase proliferation, viability, and apoptosis resistance in PASMCs. In PASMCs transfected with Raptor–small interfering RNA or treated with spironolactone/eplerenone, aldosterone or pulmonary arterial plasma from patients with PAH failed to increase p70S6K activation or to induce cell survival in vitro. Optimal inhibition of pulmonary arteriole Raptor was achieved by treatment with Staramine-monomethoxy polyethylene glycol that was formulated with Raptor-small interfering RNA plus spironolactone in vivo, which decreased arteriole muscularization and pulmonary hypertension in 2 experimental animal models of PAH in vivo. Up-regulation of mTORC1 by aldosterone is a critical pathobiologic mechanism that controls PASMC survival to promote hypertrophic vascular remodeling and PAH.—Aghamohammadzadeh, R., Zhang, Y.-Y., Stephens, T. E., Arons, E., Zaman, P., Polach, K. J., Matar, M., Yung, L.-M., Yu, P. B., Bowman, F. P., Opotowsky, A. R., Waxman, A. B., Loscalzo, J., Leopold, J. A., Maron, B. A. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension. PMID:27006450

Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension.

PubMed

Aghamohammadzadeh, Reza; Zhang, Ying-Yi; Stephens, Thomas E; Arons, Elena; Zaman, Paula; Polach, Kevin J; Matar, Majed; Yung, Lai-Ming; Yu, Paul B; Bowman, Frederick P; Opotowsky, Alexander R; Waxman, Aaron B; Loscalzo, Joseph; Leopold, Jane A; Maron, Bradley A

2016-07-01

Activation of the mammalian target of rapamycin complex 1 (mTORC1) subunit Raptor induces cell growth and is a downstream target of Akt. Elevated levels of aldosterone activate Akt, and, in pulmonary arterial hypertension (PAH), correlate with pulmonary arteriole thickening, which suggests that mTORC1 regulation by aldosterone may mediate adverse pulmonary vascular remodeling. We hypothesized that aldosterone-Raptor signaling induces abnormal pulmonary artery smooth muscle cell (PASMC) survival patterns to promote PAH. Remodeled pulmonary arterioles from SU-5416/hypoxia-PAH rats and monocrotaline-PAH rats with hyperaldosteronism expressed increased levels of the Raptor target, p70S6K, which provided a basis for investigating aldosterone-Raptor signaling in human PASMCs. Aldosterone (10(-9) to 10(-7) M) increased Akt/mTOR/Raptor to activate p70S6K and increase proliferation, viability, and apoptosis resistance in PASMCs. In PASMCs transfected with Raptor-small interfering RNA or treated with spironolactone/eplerenone, aldosterone or pulmonary arterial plasma from patients with PAH failed to increase p70S6K activation or to induce cell survival in vitro Optimal inhibition of pulmonary arteriole Raptor was achieved by treatment with Staramine-monomethoxy polyethylene glycol that was formulated with Raptor-small interfering RNA plus spironolactone in vivo, which decreased arteriole muscularization and pulmonary hypertension in 2 experimental animal models of PAH in vivo Up-regulation of mTORC1 by aldosterone is a critical pathobiologic mechanism that controls PASMC survival to promote hypertrophic vascular remodeling and PAH.-Aghamohammadzadeh, R., Zhang, Y.-Y., Stephens, T. E., Arons, E., Zaman, P., Polach, K. J., Matar, M., Yung, L.-M., Yu, P. B., Bowman, F. P., Opotowsky, A. R., Waxman, A. B., Loscalzo, J., Leopold, J. A., Maron, B. A. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension. © FASEB.

Pulmonary Artery Aneurysm/Pseudoaneurysm, a Delayed Complication of Lung Abscess: A Case Report.

PubMed

Oguma, Tsuyoshi; Morise, Masahiro; Harada, Kazuki; Tanaka, Jun; Sato, Masako; Horio, Yukihiro; Takiguchi, Hiroto; Tomomatsu, Hiromi; Tomomatsu, Katsuyoshi; Takihara, Takahisa; Niimi, Kyoko; Hayama, Naoki; Aoki, Takuya; Urano, Tetsuya; Ito, Chihiro; Koizumi, Jun; Asano, Koichiro

2015-09-20

Massive hemoptysis mostly arises from the bronchial arteries; however, bleeding can also occur from a lesion in injured pulmonary arteries, such as pulmonary artery aneurysm/pseudoaneurysm (PAA/PAP), during pulmonary infection. A 66-year-old man was admitted with a diagnosis of lung abscess in the right lower lobe that was complicated with pyothorax. Intravenous administration of antibiotics and thoracic drainage successfully controlled the infection and inflammation until day 16, when the patient began to exhibit hemoptysis and bloody pleural effusion. Enhanced computed tomography (CT) with multi-planer reconstruction (MPR) images showed a highly enhanced mass inside the abscess fed by the pulmonary artery, suggesting PAA/PAP. Pulmonary angiography confirmed PAA/PAP, and embolization with coils successfully stopped both the bleeding into the sputum and pleural effusion, with a collapsed aneurysm visible on chest CT scan. Clinicians should consider the possibility of PAA/PAP in the differential diagnosis of hemoptysis during the treatment of patients with lung abscess. MPR CT is helpful for the diagnosis of PAA/PAP and its feeding vessels.

Circulating big endothelin-1: an active role in pulmonary thromboendarterectomy?

PubMed

Langer, Frank; Bauer, Michael; Tscholl, Dietmar; Schramm, Rene; Kunihara, Takashi; Lausberg, Henning; Georg, Thomas; Wilkens, Heinrike; Schäfers, Hans-Joachim

2005-11-01

Pulmonary thromboendarterectomy is an effective treatment for patients with chronic thromboembolic pulmonary hypertension. The early postoperative course may be associated with pulmonary vasoconstriction and profound systemic vasodilation. We investigated the potential involvement of endothelins in these hemodynamic alterations. Seventeen patients with chronic thromboembolic pulmonary hypertension (pulmonary vascular resistance, 1015 +/- 402 dyne x s x cm(-5) [mean +/- SD]) underwent pulmonary thromboendarterectomy with cardiopulmonary bypass and deep hypothermic circulatory arrest. Peripheral arterial blood samples were drawn before sternotomy, during cardiopulmonary bypass before and after deep hypothermic circulatory arrest, and 0, 8, 16, and 24 hours after surgery and were analyzed for big endothelin-1. The patients were divided into 2 groups according to whether their preoperative big endothelin-1 plasma level was above or below the cutoff point of 2.1 pg/mL, as determined by receiver operating characteristic curve analysis (group A, big endothelin-1 <2.1 pg/mL, n = 8; group B, big endothelin-1 > or =2.1 pg/mL, n = 9). Patients in group B, with higher preoperative big endothelin-1 levels (3.2 +/- 1.0 pg/mL vs 1.5 +/- 0.4 pg/mL; P < .001), were poorer operative candidates (preoperative mean pulmonary artery pressure, 51.3 +/- 7.1 mm Hg vs 43.6 +/- 6.2 mm Hg; P = .006) and had a poorer outcome (mean pulmonary artery pressure 24 hours after surgery, 32.6 +/- 9.5 mm Hg vs 21.8 +/- 6.2 mm Hg; P < .001). Positive correlations were found between preoperative big endothelin-1 levels and preoperative mean pulmonary artery pressure (r = 0.56; P = .02) as well as postoperative mean pulmonary artery pressure at 0 hours (r = 0.70; P = .002) and 24 hours (r = 0.63; P = .006) after surgery. Preoperative big endothelin-1 levels predicted outcome (postoperative mean pulmonary artery pressure at 24 hours after surgery) after pulmonary thromboendarterectomy (area under the receiver operating characteristic curve, 0.85). Peak big endothelin-1 levels also correlated with maximal vasopressor dosage (r = 0.65; P = .004). Preoperative big endothelin-1 levels seem to correlate with the hemodynamic alterations observed in pulmonary thromboendarterectomy and may be used to predict hemodynamic outcome after pulmonary thromboendarterectomy.

An unusual neonatal presentation of anomalous origin of the left coronary artery arising from the pulmonary artery.

PubMed

Garty, Y; Guri, A; Shinwell, E S; Matitiau, A

2008-01-01

We describe a previously unreported neonatal presentation of an anomalous origin of the left coronary artery arising from the pulmonary artery. This is a full-term female infant after normal pregnancy and delivery. The baby was diagnosed at 2 days of age due to weak femoral pulses noted on the routine nursery discharge examination. The cardiac examination revealed weak pulses everywhere and mild tachypnea and tachycardia. An electrocardiogram showed clear signs of ischemia. Echocardiography demonstrated an anomalous origin of the left coronary artery arising from the pulmonary artery with bidirectional blood flow. There was a severely depressed left ventricular function and mild mitral valve regurgitation. At 4 days of age, the infant underwent complete successful surgical repair with reimplantation of the anomalous coronary artery to the aorta. She recovered slowly but well. Fifteen months later she is doing well with no cardiac residua. A neonatal presentation is very unusual due to protective high pulmonary resistance after birth, with gradual decline in pressure and gradual onset of heart failure. This case may be related to an unusually rapid drop in pulmonary vascular resistance causing very early cardiac ischemia. (c) 2007 S. Karger AG, Basel.

Obstruction of the Aorta and Left Pulmonary Artery After Gianturco Coil Occlusion of Patent Ductus Arteriosus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuo, H.-Cg; Ko, Sheung-Fat; Wu, Yu-Tsun

We report an unusual case of simultaneous obstruction of the left pulmonary artery and descending thoracic aorta after Gianturco coil occlusion in a 15-month-old boy. The diagnosis was made by echocardiography and cardiac angiography. At surgery, thrombi coating on the protruded parts of the Gianturco coil in the pulmonary artery and aorta were found.

Alveolar recruitment manoeuvre is safe in children prone to pulmonary hypertensive crises following open heart surgery: a pilot study.

PubMed

Amorim, Erica de Freitas; Guimaraes, Viviane Assuncao; Carmona, Fabio; Carlotti, Ana Paula de Carvalho Panzeri; Manso, Paulo Henrique; Ferreira, Cesar Augusto; Klamt, Jyrson Guilherme; Vicente, Walter Villela de Andrade

2014-05-01

To test the tolerance and safety of an alveolar recruitment manoeuvre performed in the immediate postoperative period of corrective open heart surgery in children with congenital heart disease associated with excessive pulmonary blood flow and pulmonary arterial hypertension due to left-to-right shunt. Ten infants aged 1-24 months with congenital heart disease associated with excessive pulmonary blood flow and pulmonary artery hypertension (mean pulmonary artery pressure ≥ 25 mmHg) were evaluated. The alveolar recruitment manoeuvre was performed in the operating theatre right after skin closure, and consisted of three successive stages of 30 s each, intercalated by a 1-min interval of baseline ventilation. Positive end-expiratory pressure was set to 10 cmH2O in the first stage and to 15 cmH2O in the two last ones, while the peak inspiratory pressure was kept at to 30 cmH2O in the first stage and at 35 cmH2O in the latter ones. Haemodynamic and respiratory variables were recorded. There was a slight but significant increase in mean pulmonary artery pressure from baseline to Stage 3 (P = 0.0009), as well as between Stages 1 and 2 (P = 0.0001), and 1 and 3 (P = 0.001), with no significant difference between Stages 2 and 3 (P = 0.06). Upon completion of the third stage, there were significant increases in arterial haemoglobin saturation as measured by pulse oximetry (P = 0.0009), arterial blood partial pressure of oxygen (P = 0.04), venous blood oxygen saturation of haemoglobin (P = 0.03) and arterial oxygen partial pressure over inspired oxygen fraction ratio (P = 0.04). A significant reduction in arterial blood partial pressure of carbon dioxide (P = 0.01) and in end tidal carbon dioxide also occurred (P = 0.009). The manoeuvre was well tolerated and besides a slight and transitory elevation in mean pulmonary artery, no other adverse haemodynamic or ventilatory effect was elicited. The alveolar recruitment manoeuvre seemed to be safe and well tolerated immediately after open heart surgery in infants liable to pulmonary hypertensive crises.

Dispersion of transit times within the pulmonary vasculature from microfocal angiograms

NASA Astrophysics Data System (ADS)

Clough, Anne V.; Wang, Qiong; Haworth, Steven T.; Linehan, John H.; Roerig, David T.; Hanger, Christopher C.; Dawson, Christopher A.

1997-05-01

The site and mechanism of the dispersion of blood transit times within the pulmonary vascular bed can be described using x-ray angiography images of bolus passage through the pulmonary vasculature. Time-absorbance curves from the lobar inlet artery and outlet vein, various locations within the arterial and venous trees, and regions of the microvasculature were acquired from the images. The overall dispersion within the lung lobe was determined from the inlet arterial and outlet venous curves by examining the difference in their first and second moments, mean transit time and variance, respectively. Subsequently, the moments at each location within the arterial tree were calculated and compared to those of the lobar inlet artery curve. The transit time variance imparted on the bolus as it traveled through the pulmonary arterial tree upstream from the smallest measured arteries was < 5 percent of the variance attributable to transit through the total lung lobe vascular bed. Similar results were obtained for the venous pathways using reverse-flow conditions. Regional capillary mean transit time and variance were obtained from the measured microvascular residue curves using a mass-balance model. These results suggest that most of the bolus dispersion occurs within the pulmonary capillary bed rather than in large feeding arteries or draining veins.

Journal Club: Comparison of assessment of preoperative pulmonary vasculature in patients with non-small cell lung cancer by non-contrast- and 4D contrast-enhanced 3-T MR angiography and contrast-enhanced 64-MDCT.

PubMed

Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Seki, Shinichiro; Sugimura, Kazuro

2014-03-01

The purpose of this article is to prospectively and directly compare the capabilities of non-contrast-enhanced MR angiography (MRA), 4D contrast-enhanced MRA, and contrast-enhanced MDCT for assessing pulmonary vasculature in patients with non-small cell lung cancer (NSCLC) before surgical treatment. A total of 77 consecutive patients (41 men and 36 women; mean age, 71 years) with pathologically proven and clinically assessed stage I NSCLC underwent thin-section contrast-enhanced MDCT, non-contrast-enhanced and contrast-enhanced MRA, and surgical treatment. The capability for anomaly assessment of the three methods was independently evaluated by two reviewers using a 5-point visual scoring system, and final assessment for each patient was made by consensus of the two readers. Interobserver agreement for pulmonary arterial and venous assessment was evaluated with the kappa statistic. Then, sensitivity, specificity, and accuracy for the detection of anomalies were directly compared among the three methods by use of the McNemar test. Interobserver agreement for pulmonary artery and vein assessment was substantial or almost perfect (κ=0.72-0.86). For pulmonary arterial and venous variation assessment, there were no significant differences in sensitivity, specificity, and accuracy among non-contrast-enhanced MRA (pulmonary arteries: sensitivity, 77.1%; specificity, 97.4%; accuracy, 87.7%; pulmonary veins: sensitivity, 50%; specificity, 98.5%; accuracy, 93.2%), 4D contrast-enhanced MRA (pulmonary arteries: sensitivity, 77.1%; specificity, 97.4%; accuracy, 87.7%; pulmonary veins: sensitivity, 62.5%; specificity, 100.0%; accuracy, 95.9%), and thin-section contrast-enhanced MDCT (pulmonary arteries: sensitivity, 91.4%; specificity, 89.5%; accuracy, 90.4%; pulmonary veins: sensitivity, 50%; specificity, 100.0%; accuracy, 95.9%) (p>0.05). Pulmonary vascular assessment of patients with NSCLC before surgical resection by non-contrast-enhanced MRA can be considered equivalent to that by 4D contrast-enhanced MRA and contrast-enhanced MDCT.

GPCRs in pulmonary arterial hypertension: tipping the balance.

PubMed

Iyinikkel, Jean; Murray, Fiona

2018-02-21

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease characterised by increased pulmonary vascular resistance and excessive proliferation of pulmonary artery smooth muscle cells (PASMC). GPCRs, which are attractive pharmacological targets, are important regulators of pulmonary vascular tone and PASMC phenotype. PAH is associated with the altered expression and function of a number of GPCRs in the pulmonary circulation, which leads to the vasoconstriction and proliferation of PASMC and thereby contributes to the imbalance of pulmonary vascular tone associated with PAH; drugs targeting GPCRs are currently used clinically to treat PAH and extensive preclinical work supports the utility of a number of additional GPCRs. Here we review how GPCR expression and function changes with PAH and discuss why GPCRs continue to be relevant drug targets for the disease. © 2018 The British Pharmacological Society.

Determination of lung segments in computed tomography images using the Euclidean distance to the pulmonary artery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoecker, Christina; Moltz, Jan H.; Lassen, Bianca

Purpose: Computed tomography (CT) imaging is the modality of choice for lung cancer diagnostics. With the increasing number of lung interventions on sublobar level in recent years, determining and visualizing pulmonary segments in CT images and, in oncological cases, reliable segment-related information about the location of tumors has become increasingly desirable. Computer-assisted identification of lung segments in CT images is subject of this work.Methods: The authors present a new interactive approach for the segmentation of lung segments that uses the Euclidean distance of each point in the lung to the segmental branches of the pulmonary artery. The aim is tomore » analyze the potential of the method. Detailed manual pulmonary artery segmentations are used to achieve the best possible segment approximation results. A detailed description of the method and its evaluation on 11 CT scans from clinical routine are given.Results: An accuracy of 2–3 mm is measured for the segment boundaries computed by the pulmonary artery-based method. On average, maximum deviations of 8 mm are observed. 135 intersegmental pulmonary veins detected in the 11 test CT scans serve as reference data. Furthermore, a comparison of the presented pulmonary artery-based approach to a similar approach that uses the Euclidean distance to the segmental branches of the bronchial tree is presented. It shows a significantly higher accuracy for the pulmonary artery-based approach in lung regions at least 30 mm distal to the lung hilum.Conclusions: A pulmonary artery-based determination of lung segments in CT images is promising. In the tests, the pulmonary artery-based determination has been shown to be superior to the bronchial tree-based determination. The suitability of the segment approximation method for application in the planning of segment resections in clinical practice has already been verified in experimental cases. However, automation of the method accompanied by an evaluation on a larger number of test cases is required before application in the daily clinical routine.« less

[Effect of acidic oligosaccharides on P-selectin of pulmonary hypertensive rats induced by monocrotaline].

PubMed

Feng, Z; Hu, Y; An, N N; Feng, W J; Hu, T; Mao, Y J

2018-02-12

Objective: To observe the effects of acidic oligosaccharides (AOS) on P-selectin levels in the serum and the pulmonary arteries of pulmonary hypertensive rats induced by monocrotaline. Methods: Sixty healthy adult male Sprague-Dawley rats were randomly divided into control group ( n =10), model group ( n =10), Alprostadil group ( n =10), low-dose AOS group (AOS-L, n =10), medium-dose AOS group (AOS-M, n =10) and high-dose AOS group (AOS-H, n =10). The rat model of pulmonary arterial hypertension was made by a single intraperitoneal injection of monocrotaline(60 mg/kg). Five weeks after injection, pulmonary arterial (PA) acceleration time (PAT) and ejection time (ET) were measured by color Doppler ultrasound. Then, the Alprostadil group was treated by Alprostadil 5 μg·kg(-1)·d(-1)intraperitoneally. Acidic oligosaccharides was administered by intraperitoneal injection to rats in the AOS-L group(5 kg(-1)·d(-1)), AOS-M group (10 mg·kg(-1)·d(-1))and AOS-H group (20 mg·kg(-1)·d(-1)). Control group and model group were given normal saline instead. At the end of experiments, the death rate was recorded and PAT/ET was measured. We calculated the right ventricular hypertrophy index (RVHI) of all rats sacrificed under anesthesia. Precision-cut lung slices were stained with HE for observation of the structure of middle and small arteries. The expression level of P-selectin in serum and pulmonary arterial tissues were detected by ELISA and Western blot respectively. Results: AOS significantly increased the level of PAT/ET ( P <0.01), and attenuated RVHI ( P <0.01). AOS significantly improved intima-media proliferation in small-to medium-sized pulmonary arteries, and attenuated perivascular inflammation. AOS and Alprostadil significantly down-regulated the protein expression of P-selectin in serum and pulmonary arteries ( P <0.01). Conclusion: In this rat model of monocrotaline-induced pulmonary hypertension, AOS decreased the expressions of P-selectin in serum and pulmonary arteries in a dose-dependent manner.

Role of Kv7 channels in responses of the pulmonary circulation to hypoxia.

PubMed

Sedivy, Vojtech; Joshi, Shreena; Ghaly, Youssef; Mizera, Roman; Zaloudikova, Marie; Brennan, Sean; Novotna, Jana; Herget, Jan; Gurney, Alison M

2015-01-01

Hypoxic pulmonary vasoconstriction (HPV) is a beneficial mechanism that diverts blood from hypoxic alveoli to better ventilated areas of the lung, but breathing hypoxic air causes the pulmonary circulation to become hypertensive. Responses to airway hypoxia are associated with depolarization of smooth muscle cells in the pulmonary arteries and reduced activity of K(+) channels. As Kv7 channels have been proposed to play a key role in regulating the smooth muscle membrane potential, we investigated their involvement in the development of HPV and hypoxia-induced pulmonary hypertension. Vascular effects of the selective Kv7 blocker, linopirdine, and Kv7 activator, flupirtine, were investigated in isolated, saline-perfused lungs from rats maintained for 3-5 days in an isobaric hypoxic chamber (FiO2 = 0.1) or room air. Linopirdine increased vascular resistance in lungs from normoxic, but not hypoxic rats. This effect was associated with reduced mRNA expression of the Kv7.4 channel α-subunit in hypoxic arteries, whereas Kv7.1 and Kv7.5 were unaffected. Flupirtine had no effect in normoxic lungs but reduced vascular resistance in hypoxic lungs. Moreover, oral dosing with flupirtine (30 mg/kg/day) prevented short-term in vivo hypoxia from increasing pulmonary vascular resistance and sensitizing the arteries to acute hypoxia. These findings suggest a protective role for Kv7.4 channels in the pulmonary circulation, limiting its reactivity to pressor agents and preventing hypoxia-induced pulmonary hypertension. They also provide further support for the therapeutic potential of Kv7 activators in pulmonary vascular disease. Copyright © 2015 the American Physiological Society.

Long-term effects of prenatal hypoxia on endothelium-dependent relaxation responses in pulmonary arteries of adult sheep.

PubMed

Liu, Jie; Gao, Yuansheng; Negash, Sewite; Longo, Lawrence D; Raj, J Usha

2009-03-01

Chronic hypoxia during the course of pregnancy is a common insult to the fetus. However, its long-term effect on the pulmonary vasculature in adulthood has not been described. In this study, the vasorelaxation responses of conduit pulmonary arteries in adult female sheep that were chronically hypoxic as fetuses and raised postnatally at sea level were investigated. Vessel tension studies revealed that endothelium-dependent relaxation responses were attenuated in pulmonary arteries from adult sheep that experienced prenatal hypoxia. Endothelial nitric oxide synthase (eNOS) protein expression was unchanged, but eNOS activity was significantly decreased in pulmonary arteries from prenatally hypoxic sheep. Protein expression of eNOS partners, caveolin-1, calmodulin, and heat shock protein 90 (Hsp90) did not change following prenatal hypoxia. However, the association between eNOS and caveolin-1, its inhibitory binding partner, was significantly increased, whereas association between eNOS and its stimulatory partners calmodulin and Hsp90 was greatly decreased. Furthermore, phosphorylation of Ser(1177) in eNOS decreased, whereas phosphorylation of Thr(495) increased, in the prenatally hypoxic pulmonary arteries, events that are related to eNOS activity. These data demonstrate that prenatal hypoxia results in persistent abnormalities in endothelium-dependent relaxation responses of pulmonary arteries in adult sheep due to decreased eNOS activity resulting from altered posttranslational regulation.

Long-term effects of prenatal hypoxia on endothelium-dependent relaxation responses in pulmonary arteries of adult sheep

PubMed Central

Liu, Jie; Gao, Yuansheng; Negash, Sewite; Longo, Lawrence D.; Raj, J. Usha

2009-01-01

Chronic hypoxia during the course of pregnancy is a common insult to the fetus. However, its long-term effect on the pulmonary vasculature in adulthood has not been described. In this study, the vasorelaxation responses of conduit pulmonary arteries in adult female sheep that were chronically hypoxic as fetuses and raised postnatally at sea level were investigated. Vessel tension studies revealed that endothelium-dependent relaxation responses were attenuated in pulmonary arteries from adult sheep that experienced prenatal hypoxia. Endothelial nitric oxide synthase (eNOS) protein expression was unchanged, but eNOS activity was significantly decreased in pulmonary arteries from prenatally hypoxic sheep. Protein expression of eNOS partners, caveolin-1, calmodulin, and heat shock protein 90 (Hsp90) did not change following prenatal hypoxia. However, the association between eNOS and caveolin-1, its inhibitory binding partner, was significantly increased, whereas association between eNOS and its stimulatory partners calmodulin and Hsp90 was greatly decreased. Furthermore, phosphorylation of Ser1177 in eNOS decreased, whereas phosphorylation of Thr495 increased, in the prenatally hypoxic pulmonary arteries, events that are related to eNOS activity. These data demonstrate that prenatal hypoxia results in persistent abnormalities in endothelium-dependent relaxation responses of pulmonary arteries in adult sheep due to decreased eNOS activity resulting from altered posttranslational regulation. PMID:19136582

Isolated Human Pulmonary Artery Structure and Function Pre- and Post-Cardiopulmonary Bypass Surgery.

PubMed

Dora, Kim A; Stanley, Christopher P; Al Jaaly, Emad; Fiorentino, Francesca; Ascione, Raimondo; Reeves, Barnaby C; Angelini, Gianni D

2016-02-23

Pulmonary dysfunction is a known complication after cardiac surgery using cardiopulmonary bypass, ranging from subclinical functional changes to prolonged postoperative ventilation, acute lung injury, and acute respiratory distress syndrome. Whether human pulmonary arterial function is compromised is unknown. The aim of the present study was to compare the structure and function of isolated and cannulated human pulmonary arteries obtained from lung biopsies after the chest was opened (pre-cardiopulmonary bypass) to those obtained at the end of cardiopulmonary bypass (post-cardiopulmonary bypass) from patients undergoing coronary artery bypass graft surgery. Pre- and post-cardiopulmonary bypass lung biopsies were received from 12 patients undergoing elective surgery. Intralobular small arteries were dissected, cannulated, pressurized, and imaged using confocal microscopy. Functionally, the thromboxane mimetic U46619 produced concentration-dependent vasoconstriction in 100% and 75% of pre- and post-cardiopulmonary bypass arteries, respectively. The endothelium-dependent agonist bradykinin stimulated vasodilation in 45% and 33% of arteries pre- and post-cardiopulmonary bypass, respectively. Structurally, in most arteries smooth muscle cells aligned circumferentially; live cell viability revealed that although 100% of smooth muscle and 90% of endothelial cells from pre-cardiopulmonary bypass biopsies had intact membranes and were considered viable, only 60% and 58%, respectively, were viable from post-cardiopulmonary bypass biopsies. We successfully investigated isolated pulmonary artery structure and function in fresh lung biopsies from patients undergoing heart surgery. Pulmonary artery contractile tone and endothelium-dependent dilation were significantly reduced in post-cardiopulmonary bypass biopsies. The decreased functional responses were associated with reduced cell viability. URL: http://www.isrctn.com/ISRCTN34428459. Unique identifier: ISRCTN 34428459. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Does corticosteroid therapy impact fetal pulmonary artery blood flow in women at risk for preterm birth?

PubMed

Lindsley, William; Hale, Richard; Spear, Ashley; Adusumalli, Jasvant; Singh, Jasbir; DeStefano, Kimberly; Haeri, Sina

2015-09-01

Maternal corticosteroid administration in pregnancy is known to enhance fetal lung maturity in at risk fetuses. The aim of this study was to test the hypothesis that corticosteroid therapy alters fetal pulmonary blood flow in pregnancies at risk for preterm birth (PTB). We prospectively evaluated main fetal pulmonary artery (MPA) blood flow in pregnant women at risk for PTB and treated with corticosteroids (betamethasone), compared to an uncomplicated cohort without steroid therapy. The Doppler indices of interest included Peak Systolic Velocity (PSV), Resistive Index (RI), Pulsatility Index (PI), Systolic/Diastolic ratio (S/D ratio), Acceleration Time (AT), and Acceleration Time/Ejection Time Ratio (AT/ET ratio), with the latter serving as the primary outcomes due to its stability irrespective of gestational age. When compared with controls, fetuses treated with corticosteroids demonstrated significantly decreased pulmonary artery acceleration time (median: 28.89 (22.22-51.11) vs. 33.33 (22.20-57.00), p=0.006), while all other indices remained similar. We found no difference in pulmonary blood flow between fetuses who developed respiratory distress syndrome (RDS) and those that did not (31.56 +/- 6.842 vs. 32.36 +/- 7.265, p= 0.76). Our data demonstrate altered fetal pulmonary blood flow with corticosteroid therapy, possibly due to increased arterial elastance brought on by medication effect, which leads to the decreased acceleration time or possible gestational age affect. Contrary to a recent report, we did not observe any Doppler differences in fetuses with RDS, which underscores the need for further examination of this proposed association.

Impact of Chronic Hypoxia on Proximal Pulmonary Artery Wave Propagation and Mechanical Properties in Rats.

PubMed

Su, Junjing; Logan, Charmilie C; Hughes, Alun D; Parker, Kim H; Dhutia, Niti M; Danielsen, Carl Christian; Simonsen, Ulf

2018-03-16

Arterial stiffness and wave reflection are important components of the ventricular afterload. Therefore, we aimed to assess the arterial wave characteristics and mechanical properties of the proximal pulmonary arteries (PAs) in the hypoxic pulmonary hypertensive rat model. After 21 days in normoxic or hypoxic chambers (24 animals in each group), the animals underwent transthoracic echocardiography and pulmonary artery catheterization with a dual-tipped pressure and Doppler flow sensor wire. Wave intensity analysis (WIA) was performed. Artery rings obtained from the pulmonary trunk, right and left PAs and the aorta were subjected to a tensile test to rupture. Collagen and elastin content was determined. In hypoxic rats, proximal PA wall thickness, collagen content, tensile strength per unit collagen, maximal elastic modulus and wall viscosity increased; while the elastin:collagen ratio and arterial distensibility decreased. Arterial pulse wave velocity was also increased and the increase was more prominent in vivo than ex vivo. Wave intensity was similar in the hypoxic and normoxic animals with negligible wave reflection. In contrast, aortic maximal elastic modulus remained unchanged, while the wall viscosity decreased. There was no evidence of altered arterial wave propagation in the proximal PAs of hypoxic rats, while the extracellular matrix protein composition altered and the collagen tensile strength increased. This was accompanied by altered mechanical properties in vivo and ex vivo.

Oxygen saturation and lactate concentration gradient from the right atrium to the pulmonary artery in the immediate postoperative following cardiac surgery with extracorporeal circulation.

PubMed

Pendino, Juan Carlos; Hess, Leonardo; Beltrame, Sergio; Castillo, Gonzalo Aldamiz-Echevarría; Trujillo, John

2017-01-01

This prospective study aimed to characterize the changes in blood lactate concentration and blood oxygen saturation in patients during the immediate postoperative period of cardiac surgery with extracorporeal circulation. Blood samples were collected from 35 patients in a rapid and random order from the arterial line and from the proximal and distal port of a pulmonary artery catheter. The results showed no statistically significant differences between the blood oxygen saturation in the right atrium (72% ± 0.11%) and the blood oxygen saturation in the pulmonary artery (71% ± 0.08%). The blood lactate concentration in the right atrium was 1.7mmol/L ± 0.5mmol/L, and the blood lactate concentration in the pulmonary artery was 1.6mmol/L ± 0.5mmol/L (p < 0.0005). The difference between the blood lactate concentration in the right atrium and the blood lactate concentration in the pulmonary artery might be a consequence of the low blood lactate concentration in the blood from the coronary sinus, as it constitutes an important substrate for the myocardium during this period. The lack of differences between the blood oxygen saturation in the right atrium and the percentage of blood oxygen saturation in the pulmonary artery suggests a lower oxygen extraction by the myocardium given a lower oxygen consumption.

The induction of nitric oxide-mediated relaxation of human isolated pulmonary arteries by PACAP

PubMed Central

Cardell, Lars Olaf; Hjert, Ola; Uddman, Rolf

1997-01-01

The effects of pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) were analysed in human isolated circular segments of pulmonary arteries. Guinea-pig pulmonary arteries were used for comparison. The responses obtained were analysed in relation to the vascular endothelium and the nitric oxide (NO) synthase inhibitor NG-monomethyl L-arginine (L-NMMA).PACAP and VIP induced concentration-dependent relaxations of precontracted pulmonary arteries. The maximal dilator response (Imax,%) and the potency (pEC50 value) were the same for both peptides, and there were no differences in the effects obtained on human and guinea-pig segments. PACAP and VIP were both more potent that acetylcholine (ACh).Removal of the vascular endothelium abolished the PACAP induced dilator response in pulmonary arteries from both species. The VIP induced dilatation was unaffected, whereas the response to ACh was abolished. L-NMMA given before PACAP inhibited the dilatation. Furthermore, L-NMMA also reversed the dilatation already induced by PACAP and excess concentrations of L-arginine restored the dilator response of the L-NMMA treated arteries.PACAP is a potent dilator of human pulmonary arteries. Although the dilator effect seems to be similar in amplitude to the one induced by VIP, the present results suggest differences in the underlying mechanisms of action (endothelium-dependency) between the two peptides. PMID:9134222

A 50-year-old woman with haemoptysis, cough and tachypnea: cholesterol pneumonia accompanying with pulmonary artery hypertension.

PubMed

Li, Mengxi; Zhang, Nuofu; Zhou, Ying; Li, Jinhui; Gu, Yingying; Wang, Jian; Liu, Chunli

2017-03-01

Lipoid pneumonia is an uncommon disease caused by the presence of lipid in the alveoli. Here we described a case of a 50-year-old woman with haemoptysis, cough and tachypnea, who was diagnosed with cholesterol pneumonia accompanying with pulmonary artery hypertension. The extremely high pulmonary artery pressure achieved, in this case, is alarming and should alert the physicians that the cholesterol pneumonia may be one of the underlying causes of pulmonary artery hypertension. After a treatment of methylprednisolone, her clinical symptoms were significantly improved, which suggested that steroid might be a promising therapeutic for patients with cholesterol pneumonia. © 2015 John Wiley & Sons Ltd.

Intralober pulmonary sequestration with arterial supply from two different origins: a case report.

PubMed

Erden, Ersin Sukru; Yetim, Tulin Durgun; Balci, Ali; Akcay, Adnan Burak; Hakverdi, Sibel; Demirkose, Mesut

2012-01-01

Pulmonary sequestration is a rare anomaly, which does not have a connection with the bronchial system and gets its blood supply, generally, from the aorta or its branches. Anatomically, two different forms were described: intralobar and extralobar. Although 74% of intralobar pulmonary sequestrations get their blood supply from the descending thoracic aorta, they may get their blood supply from different arteries. Furthermore, there is more than one arterial anomaly in 14.8% of cases. We report an intralobar pulmonary sequestration, in which arterial blood supply is from two different origins (Arcus aorta and celiac trunk). To the best of our knowledge, this is the first case in the literature.

Liver hydatid cyst leading to bilateral pulmonary artery embolism and bilateral multiple pulmonar echinococcosis via inferior vena cava: report of a case.

PubMed

Bayaroğullari, Hanifi; Davran, Ramazan; Cavuş, Yeliz; Yetim, Tülin Durgun; Evirgen, Ömer

2013-01-01

Hydatid disease (HD) is a worldwide parasitic disease. Echinococcosis may involve many organs but affect most commonly liver and lungs. The location of echinococcal cysts inside pulmonary artery is extremely rare. Radiologic findings range from purely cystic lesions to a completely solid appearance. Hydatid cysts (HC) can be solitary or multiple and varies size. Pulmonary artery embolism of HC can be symptomatic or asymptomatic. When symptomatic, we see the chest pain, dyspnea, cough, hemoptysis and sometimes acute cor pulmonale or sudden death secondary to massive giant pulmonary artery embolism of HC. Copyright © 2013 Elsevier Inc. All rights reserved.

Outflow tract septation and the aortic arch system in reptiles: lessons for understanding the mammalian heart.

PubMed

Poelmann, Robert E; Gittenberger-de Groot, Adriana C; Biermans, Marcel W M; Dolfing, Anne I; Jagessar, Armand; van Hattum, Sam; Hoogenboom, Amanda; Wisse, Lambertus J; Vicente-Steijn, Rebecca; de Bakker, Merijn A G; Vonk, Freek J; Hirasawa, Tatsuya; Kuratani, Shigeru; Richardson, Michael K

2017-01-01

Cardiac outflow tract patterning and cell contribution are studied using an evo-devo approach to reveal insight into the development of aorto-pulmonary septation. We studied embryonic stages of reptile hearts (lizard, turtle and crocodile) and compared these to avian and mammalian development. Immunohistochemistry allowed us to indicate where the essential cell components in the outflow tract and aortic sac were deployed, more specifically endocardial, neural crest and second heart field cells. The neural crest-derived aorto-pulmonary septum separates the pulmonary trunk from both aortae in reptiles, presenting with a left visceral and a right systemic aorta arising from the unseptated ventricle. Second heart field-derived cells function as flow dividers between both aortae and between the two pulmonary arteries. In birds, the left visceral aorta disappears early in development, while the right systemic aorta persists. This leads to a fusion of the aorto-pulmonary septum and the aortic flow divider (second heart field population) forming an avian aorto-pulmonary septal complex. In mammals, there is also a second heart field-derived aortic flow divider, albeit at a more distal site, while the aorto-pulmonary septum separates the aortic trunk from the pulmonary trunk. As in birds there is fusion with second heart field-derived cells albeit from the pulmonary flow divider as the right 6th pharyngeal arch artery disappears, resulting in a mammalian aorto-pulmonary septal complex. In crocodiles, birds and mammals, the main septal and parietal endocardial cushions receive neural crest cells that are functional in fusion and myocardialization of the outflow tract septum. Longer-lasting septation in crocodiles demonstrates a heterochrony in development. In other reptiles with no indication of incursion of neural crest cells, there is either no myocardialized outflow tract septum (lizard) or it is vestigial (turtle). Crocodiles are unique in bearing a central shunt, the foramen of Panizza, between the roots of both aortae. Finally, the soft-shell turtle investigated here exhibits a spongy histology of the developing carotid arteries supposedly related to regulation of blood flow during pharyngeal excretion in this species. This is the first time that is shown that an interplay of second heart field-derived flow dividers with a neural crest-derived cell population is a variable but common, denominator across all species studied for vascular patterning and outflow tract septation. The observed differences in normal development of reptiles may have impact on the understanding of development of human congenital outflow tract malformations.

Signal transduction in the development of pulmonary arterial hypertension

PubMed Central

Malenfant, Simon; Neyron, Anne-Sophie; Paulin, Roxane; Potus, François; Meloche, Jolyane; Provencher, Steeve; Bonnet, Sébastien

2013-01-01

Pulmonary arterial hypertension (PAH) is a unique disease. Properly speaking, it is not a disease of the lung. It can be seen more as a microvascular disease occurring mainly in the lungs and affecting the heart. At the cellular level, the PAH paradigm is characterized by inflammation, vascular tone imbalance, pulmonary arterial smooth muscle cell proliferation and resistance to apoptosis and the presence of in situ thrombosis. At a clinical level, the aforementioned abnormal vascular properties alter physically the pulmonary circulation and ventilation, which greatly influence the right ventricle function as it highly correlates with disease severity. Consequently, right heart failure remains the principal cause of death within this cohort of patients. While current treatment modestly improve patients’ conditions, none of them are curative and, as of today, new therapies are lacking. However, the future holds potential new therapies that might have positive influence on the quality of life of the patient. This article will first review the clinical presentation of the disease and the different molecular pathways implicated in the pathobiology of PAH. The second part will review tomorrow's future putative therapies for PAH. PMID:24015329

Acute pulmonary edema following inflation of arterial tourniquet.

PubMed

Santhosh, M C B; Pai, R B; Rao, R P

2014-10-01

Arterial tourniquets are used as one of the methods for reducing blood loss and for allowing blood free surgical field. A 20-year-old, 45 kg healthy female with a sphere shaped pendunculated hemangioma in the popliteal fossa of her left lower limb was applied with arterial tourniquet after exsanguination. The procedure was performed under general anesthesia. Soon after exsanguination and tourniquet inflation, the patient developed pulmonary edema which subsided after deflating the tourniquet. The clinical evolution, treatment and pathophysiology of this complication are described. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Venous outflow obstruction and portopulmonary hypertension after orthotopic liver transplantation

PubMed Central

Aguirre-Avalos, Guadalupe; Covarrubias-Velasco, Marco Antonio; Rojas-Sánchez, Antonio Gerardo

2013-01-01

Patient: Female, 54 Final Diagnosis: Suprahepatic inferior vena cava anastomosis stricture Symptoms: Ascites • fatigue • lower limb edema • hepatomegaly Medication: — Clinical Procedure: — Specialty: Transplantology • Critical Care Medicine Objective: Unusual clinical course Background: Suprahepatic inferior vena cava anastomosis stricture is an unusual vascular complication after orthotopic liver transplantation with the “piggyback” technique. Clinical manifestations are dependent upon the severity of the stenosis. Portopulmonary hypertension after orthotopic liver transplantation is a complication that carries high mortality due to cardiopulmonary dysfunction. The pathogenesis of pulmonary vascular disorders after orthotopic liver transplantation remains uncertain. Case Report: We report a case of acute right heart pressure overload after surgical correction of the suprahepatic inferior vena cava anastomotic stricture in a 54-year-old woman who had preexisting pulmonary arterial hypertension associated with portal hypertension after orthotopic liver transplantation. Twenty months posttransplantation, she developed fatigue and progressive ascites. On admission, the patient had hepatomegaly, ascites, and lower limb edema. Symptoms in the patient developed gradually over time. Conclusions: Recurrent portal hypertension by vascular complications is a cause of pulmonary arterial hypertension after orthotopic liver transplantation. Clinical manifestations of suprahepatic inferior vena cava anastomotic stenosis are dependent upon their severity. Sildenafil is an effective drug for treatment of pulmonary arterial hyper-tension after portal hypertension by vascular complications. PMID:24046802

Cytoplasmic YY1 Is Associated with Increased Smooth Muscle-Specific Gene Expression

PubMed Central

Favot, Laure; Hall, Susan M.; Haworth, Sheila G.; Kemp, Paul R.

2005-01-01

Immediately after birth the adluminal vascular SMCs of the pulmonary elastic arteries undergo transient actin cytoskeletal remodeling as well as cellular de-differentiation and proliferation. Vascular smooth muscle phenotype is regulated by serum response factor, which is itself regulated in part by the negative regulator YY1. We therefore studied the subcellular localization of YY1 in arteries of normal newborn piglets and piglets affected by neonatal pulmonary hypertension. We found that YY1 localization changed during development and that expression of γ-smooth muscle actin correlated with expression of cytoplasmic rather than nuclear YY1. Analysis of the regulation of YY1 localization in vitro demonstrated that polymerized γ-actin sequestered EGFP-YY1 in the cytoplasm and that YY1 activation of c-myc promoter activity was inhibited by LIM kinase, which increases actin polymerization. Consistent with these data siRNA-mediated down-regulation of YY1 in C2C12 cells increased SM22-α expression and inhibited cell proliferation. Thus, actin polymerization controls subcellular YY1 localization, which contributes to vascular SMC proliferation and differentiation in normal pulmonary artery development. In the absence of actin depolymerization, YY1 does not relocate to the nucleus, and this lack of relocation may contribute to the pathobiology of pulmonary hypertension. PMID:16314465

Role of Reactive Oxygen Species in Neonatal Pulmonary Vascular Disease

PubMed Central

Steinhorn, Robin H.

2014-01-01

Abstract Significance: Abnormal lung development in the perinatal period can result in severe neonatal complications, including persistent pulmonary hypertension (PH) of the newborn and bronchopulmonary dysplasia. Reactive oxygen species (ROS) play a substantive role in the development of PH associated with these diseases. ROS impair the normal pulmonary artery (PA) relaxation in response to vasodilators, and ROS are also implicated in pulmonary arterial remodeling, both of which can increase the severity of PH. Recent Advances: PA ROS levels are elevated when endogenous ROS-generating enzymes are activated and/or when endogenous ROS scavengers are inactivated. Animal models have provided valuable insights into ROS generators and scavengers that are dysregulated in different forms of neonatal PH, thus identifying potential therapeutic targets. Critical Issues: General antioxidant therapy has proved ineffective in reversing PH, suggesting that it is necessary to target specific signaling pathways for successful therapy. Future Directions: Development of novel selective pharmacologic inhibitors along with nonantioxidant therapies may improve the treatment outcomes of patients with PH, while further investigation of the underlying mechanisms may enable earlier detection of the disease. Antioxid. Redox Signal. 21, 1926–1942. PMID:24350610

Pulmonary MRA: Differentiation of pulmonary embolism from truncation artifact

PubMed Central

Bannas, Peter; Schiebler, Mark L; Motosugi, Utaroh; François, Christopher J; Reeder, Scott B; Nagle, Scott K

2015-01-01

Purpose Truncation artifact (Gibbs ringing) causes central signal drop within vessels in pulmonary MRA that can be mistaken for emboli, reducing the diagnostic accuracy for pulmonary embolism (PE). We propose a quantitative approach to differentiate truncation artifact from PE. Methods Twenty-eight patients who underwent pulmonary CTA for suspected PE were recruited for pulmonary MRA. Signal intensity drops within pulmonary arteries that persisted on both arterial-phase and delayed-phase MRA were identified. The percent signal loss between the vessel lumen and central drop was measured. CTA served as the reference standard for presence of pulmonary emboli. Results A total of 65 signal intensity drops were identified on MRA. 48 (74%) of these were artifact and 17 (26%) were PE, as confirmed by CTA. Truncation artifacts had a significantly lower median signal drop than PE at both arterial-phase (26% [range 12–58%] vs. 85% [range 53–91%]) and at delayed-phase MRA (26% [range 11–55%] vs. 77% [range 47–89%]), p<0.0001 for both. ROC analyses revealed a threshold value of 51% (arterial-phase) and 47%-signal drop (delayed-phase) to differentiate between truncation artifact and PE with 100% sensitivity and >90% specificity. Conclusion Quantitative signal drop is an objective tool to help differentiate truncation artifact and pulmonary embolism in pulmonary MRA. PMID:24863886

Heterogeneous distribution of type I nitric oxide synthase in pulmonary vasculature of ovine fetus.

PubMed

Tzao, C; Nickerson, P A; Russell, J A; Noble, B K; Steinhorn, R H

2000-11-01

The nitric oxide/guanosine 3',5'-cyclic monophosphate pathway plays an essential role in mediating pulmonary vasodilation at birth. Small resistance arteries in the fetal lung are vessels of major significance in the regulation of pulmonary vascular tone. The present study is to determine that type I nitric oxide synthase (NOS-I) is present in ovine fetal pulmonary vasculature and that NOS-I is distributed heterogeneously in ovine fetal pulmonary circulation. We used reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry and NOS-I immunohistochemistry to localize NOS-I in fetal sheep lungs and showed a colocalization for NADPH-d activity with NOS-I immunoreactivity. Strong NOS-I immunoreactivity was observed exclusively in the endothelium of the terminal bronchiole and respiratory bronchiole-associated arteries. As a comparison, adult sheep lung did not show positive immunoreactivity in the pulmonary endothelium. NOS-I was absent in the umbilical or systemic arteries from the ovine fetus, whereas abundant NOS-III immunoreactivity was present in these arteries. We conclude that NOS-I is present uniquely in the ovine fetal pulmonary circulation as opposed to the adult pulmonary or the fetal systemic circulation. NOS-I is distributed heterogeneously in the ovine pulmonary vasculature. We speculate that NOS-I plays an active role in the regulation of perinatal pulmonary circulation.

Coil embolization for pulmonary artery injury caused by chest tube drainage.

PubMed

Shigefuku, Shunsuke; Kudo, Yujin; Saguchi, Toru; Maeda, Junichi

2017-05-01

Pulmonary artery injury caused by chest tube drainage is rare, but it requires prompt diagnosis to perform urgent surgical repair. We report that a 53-year-old man who suffered from pulmonary artery injury by chest tube drainage was successfully treated by coil embolization. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Transcatheter recanalization of ligated main pulmonary artery.

PubMed

Bhole, Vinay; Wright, John G C; Stumper, Oliver

2007-04-01

A 12.5-year-old boy with tricuspid atresia and quadriplegic cerebral palsy presented with increasing cyanosis after previous palliation with a cavopulmonary shunt and ligation of the main pulmonary artery (MPA). Because of severe physical disabilities he was not considered suitable for Fontan completion. He underwent successful transcatheter stent recanalization of the ligated MPA. This re-established anterograde flow to the pulmonary arteries resulting in marked improvement in saturations.

Prognostic value of cardiovascular magnetic resonance imaging measurements corrected for age and sex in idiopathic pulmonary arterial hypertension.

PubMed

Swift, Andrew J; Rajaram, Smitha; Campbell, Michael J; Hurdman, Judith; Thomas, Steve; Capener, Dave; Elliot, Charlie; Condliffe, Robin; Wild, Jim M; Kiely, David G

2014-01-01

There are limited data on the prognostic value of cardiovascular magnetic resonance measurements in idiopathic pulmonary arterial hypertension, with no studies investigating the impact of correction of cardiovascular magnetic resonance indices for age and sex on prognostic value. Consecutive patients with idiopathic pulmonary arterial hypertension underwent cardiovascular magnetic resonance imaging at 1.5T. Steady-state free precession cardiac volumes and mass measurements were corrected for age, sex, and body surface area according to reference data and prognostic significance assessed. A total of 80 patients with idiopathic pulmonary arterial hypertension were identified, and 23 patients died during the mean follow-up of 32±14 months. Corrected for age, sex, and body surface area, right ventricular end-systolic volume (P=0.004) strongly predicted mortality, independent of World Health Organization functional class, mean right atrial pressure, cardiac index, and mixed venous oxygen saturations. Consideration should be given to correcting cardiovascular magnetic resonance measures for age, sex, and body surface area, particularly given the changing demographics of patients with idiopathic pulmonary arterial hypertension. Corrected right ventricular end-systolic volume is a strong prognostic marker in idiopathic pulmonary arterial hypertension, independent of invasively derived measurements, mean right atrial pressure cardiac index, and mixed venous oxygen saturations.

[Part II: basic hemodynamic monitoring and the use of pulmonary artery catheter].

PubMed

Dias, Fernando Suparregui; Rezende, Ederlon; Mendes, Ciro Leite; Réa-Neto, Alvaro; David, Cid Marcos; Schettino, Guilherme; Lobo, Suzana Margareth Ajeje; Barros, Alberto; Silva, Eliézer; Friedman, Gilberto; Amaral, José Luiz Gomes do; Park, Marcelo; Monachini, Maristela; Oliveira, Mirella Cristine de; Assunção, Murillo Santucci César; Akamine, Nelson; Mello, Patrícia Veiga C; Pereira, Renata Andréa Pietro; Costa Filho, Rubens; Araújo, Sebastião; Félix Pinto, Sérgio; Ferreira, Sérgio; Mitushima, Simone Mattoso; Agareno, Sydney; Brilhante, Yuzeth Nóbrega de Assis

2006-03-01

Monitoring of vital functions is one of the most important tools in the management of critically ill patients. Nowadays is possible to detect and analyze a great deal of physiologic data using a lot of invasive and non-invasive methods. The intensivist must be able to select and carry out the most appropriate monitoring technique according to the patient requirements and taking into account the benefit/risk ratio. Despite the fast development of non invasive monitoring techniques, invasive hemodynamic monitoring using Pulmonary Artery Catheter still is one of the basic procedures in Critical Care. The aim was to define recommendations about clinical utility of basic hemodynamic monitoring methods and the Use of Pulmonary Artery Catheter. Modified Delphi methodology was used to create and quantify the consensus between the participants. AMIB indicated a coordinator who invited more six experts in the area of monitoring and hemodynamic support to constitute the Consensus Advisory Board. Twenty-five physicians and nurses selected from different regions of the country completed the expert panel, which reviewed the pertinent bibliography listed at the MEDLINE in the period from 1996 to 2004. Recommendations were made based on 55 questions about the use of central venous pressure, invasive arterial pressure, pulmonary artery catheter and its indications in different settings. Evaluation of central venous pressure and invasive arterial pressure, besides variables obtained by the PAC allow the understanding of cardiovascular physiology that is of great value to the care of critically ill patients. However, the correct use of these tools is fundamental to achieve the benefits due to its use.

Pulmonary arterial compliance: How and why should we measure it?

PubMed Central

Ghio, Stefano; Schirinzi, Sandra; Pica, Silvia

2015-01-01

The pulmonary circulation is a high-flow/low-pressure system, coupled with a flow generator chamber–the right ventricle–, which is relatively unable to tolerate increases in afterload. A right heart catheterization, using a fluid-filled, balloon-tipped Swan-Ganz catheter allows the measurement of all hemodynamic parameters characterizing the pulmonary circulation: the inflow pressure, an acceptable estimate the outflow pressure, and the pulmonary blood flow. However, the study of the pulmonary circulation as a continuous flow system is an oversimplification and a thorough evaluation of the pulmonary circulation requires a correct understanding of the load that the pulmonary vascular bed imposes on the right ventricle, which includes static and dynamic components. This is critical to assess the prognosis of patients with pulmonary hypertension or with heart failure. Pulmonary compliance is a measure of arterial distensibility and, either alone or in combination with pulmonary vascular resistance, gives clinicians the possibility of a good prognostic stratification of patients with heart failure or with pulmonary hypertension. The measurement of pulmonary arterial compliance should be included in the routine clinical evaluation of such patients. PMID:26779530

A model for the extended studies of hepatic hemodynamics and metabolism in swine.

PubMed

Drougas, J G; Barnard, S E; Wright, J K; Sika, M; Lopez, R R; Stokes, K A; Williams, P E; Pinson, C W

1996-12-01

To our knowledge postoperative hepatic hemodynamics and hepatic metabolism have not been fully studied on a long-term basis. Our goal was to develop a large animal model that would permit the measurement of hepatic blood flow (BF), perihepatic pressures (P), and hepatic metabolism in a long-term setting. Catheters were inserted into the jugular vein, carotid artery, pulmonary artery, hepatic vein, and portal vein (PV) of 27 commercially bred pigs; ultrasonic transit time flowmeter probes were placed around the hepatic artery and PV. Daily postoperative measurements of jugular vein P, carotid artery P, pulmonary artery P, hepatic vein P, and PVP, as well as hepatic artery BF and PVBF, were recorded for 20 days. Hepatic carbohydrate metabolism was assessed by arteriovenous difference techniques. Jugular vein P, pulmonary artery P, hepatic vein P, PVP, and heart rate reached steady-state values during the first week, with a mean +/- SEM of 1.0 +/- 0.3 mm Hg for jugular vein P, 21.4 +/- 2.1 mm Hg for pulmonary artery P, 4.3 +/- 0.4 mm Hg for HVP, 7.8 +/- 0.5 mm Hg for PVP, and 116 +/- 4 beats per minute for heart rate. Mean carotid artery P increased from 65 +/- 3 mm Hg during surgery to 94 +/- 2 mm Hg on postoperative day 1 (P < 0.001) and to a mean 101 +/- 2 mm Hg thereafter. Total hepatic BF reached a steady-state value of 1,132 +/- 187 ml/min by postoperative day 7 (P = 0.19). Over week 1 hepatic artery BF measured as a percentage of total hepatic BF decreased from 35.0 +/- 3.0% to 15.5 +/- 2.7%, and PVBF increased from 65.0 +/- 3.0% to 84.5 +/- 2.7% (P < 0.005); both variables were steady thereafter. In the hemodynamic steady state the net hepatic balances of glucose, lactate, glycerol, and alanine in 5 pigs were 9.9 +/- 4.0, -4.2 +/- 0.4, -2.3 +/- 1.1, and -0.68 +/- 0.22 micromol/kg per min respectively. The net gut (portal-drained viscera) balances of glucose, lactate, alanine, and glycerol were -2.0 +/- 2.5, 1.1 +/- 0.5, 0.73 +/- 0.18, and -0.69 +/- 0.19 micromol/kg per min respectively. Thus, a reliable large animal model was developed to study acute and chronic hepatic hemodynamics and metabolism.

The value of transthoracic echocardiography in the diagnosis of anomalous origin of the right pulmonary artery from the ascending aorta: A single center experience from China.

PubMed

Wang, Jing; Song, Yue; Cheng, Tsung O; Xie, Mingxing; Wang, Xinfang; Yuan, Li; Yang, Yali; Wang, Lei

2015-04-01

Anomalous origin of pulmonary artery (AOPA) from the ascending aorta is a rare but serious congenital cardiac malformation, which frequently involves the right pulmonary artery (RPA). We retrospectively analyzed the echocardiographic characteristics of 9 cases with anomalous origin of the right pulmonary artery from the ascending aorta (AORPA) studied from 2007 to 2014 in our institution. The results were compared with the findings at surgery. The corrective surgery was performed in all 9 cases with AORPA. The diagnosis by transthoracic echocardiography (TTE) of 8 cases with AORPA was confirmed at surgery. The coincidence rate for TTE and surgical findings was 88.9%. One case was misdiagnosed as anomalous origin of the left pulmonary artery from the ascending aorta. The anomalous RPA in all cases had a proximal origin from the posterior or lateral part of the ascending aorta in our series. The mean distance from the aortic valve to the site of origin of pulmonary artery was 16.1 ± 6.6 mm (range: 7.0 mm-24.0 mm). The mean diameter of the anomalous pulmonary artery was 9.6 ± 4.5 mm (range: 4.5 mm-17.0 mm). In 4 of 9 (44.5%) cases there were associated aortopulmonary septal defect, intact ventricular septum, patent ductus arteriosus and interruption of aortic arch (Type A), also known as the Berry's syndrome. Other associated cardiovascular abnormalities included patent ductus arteriosus, ventricular septal defect and atrial septal defect. Severe pulmonary arterial hypertension was noted in all cases. TTE plays an important role in the non-invasive and accurate diagnosis of AORPA. TTE can clearly display its site of origin and course, as well as other associated malformations and hemodynamic changes. TTE also plays an important role in the preoperative diagnosis of AORPA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Right ventricular to pulmonary artery conduit instead of modified Blalock-Taussig shunt improves postoperative hemodynamics in newborns after the Norwood operation.

PubMed

Mair, Rudolf; Tulzer, Gerald; Sames, Eva; Gitter, Roland; Lechner, Evelyn; Steiner, Jürgen; Hofer, Anna; Geiselseder, Gertraud; Gross, Christoph

2003-11-01

Perioperative mortality, prolonged postoperative recovery after the Norwood procedure, and mortality between stage I and stage II might be related to shunt physiology. A right ventricular to pulmonary artery conduit offers a banded physiology in contrast to a Blalock-Taussig shunt. The purpose of this study was to assess the hemodynamic differences and their consequences in the postoperative course between Norwood patients with a Blalock-Taussig shunt and those with a right ventricular to pulmonary artery conduit. From October 1999 until May 2002, 32 unselected consecutive patients underwent a Norwood procedure at the General Hospital Linz. The first 18 patients received a Blalock-Taussig shunt. In the remaining 14 patients we performed a right ventricular to pulmonary artery conduit. Both groups were compared. The diastolic blood pressure was significantly higher in the right ventricular to pulmonary artery conduit group (P <.001). Despite a higher FIO(2), PO(2) levels tended to be lower in the first 5 postoperative days. At the age of 3 months, catheterization laboratory data showed a lower Qp/Qs ratio in the same group (0.86 [0.78; 1] versus 1.55 [1.15; 1.6]; P =.005) and a higher dp/dt (955 [773; 1110] vs 776 [615; 907]; P =.018). (Descriptive data reflect medians and quartiles [in brackets].) Hospital survival was 72% in the Blalock-Taussig shunt group versus 93% in the right ventricular to pulmonary artery conduit group. Mortality between stage I and stage II was 23% in the Blalock-Taussig shunt group versus 0% in the right ventricular to pulmonary artery conduit group. A higher diastolic blood pressure and a lower Qp/Qs ratio were associated with a more stable and efficient circulation in patients with a right ventricular to pulmonary artery conduit. More intensive ventilatory support was necessary during the first postoperative days. We did not note any adverse effects of the ventriculotomy on ventricular performance.

Crotalaria-induced pulmonary hypertension. Uptake of 3H-thymidine by the cells of the pulmonary circulation and alveolar walls.

PubMed Central

Meyrick, B. O.; Reid, L. M.

1982-01-01

Feeding with Crotalaria spectabilis seeds induces structural changes in the pulmonary arterial circulation characteristic of pulmonary hypertension: increased medial and adventitial thickness, the appearance of muscle in smaller arteries than normal, and reduction in the number of peripheral arteries. By autoradiographic techniques, after injection of 3H-thymidine into rats fed Crotalaria for 3, 7, 14, 21, 28, or 35 days, the contribution of hyperplasia to these changes has been assessed at two levels of the pulmonary artery--the hilum and the periphery. In the hilar pulmonary artery, a biphasic increase in labeling index (LI) is seen in each cell type. After 3 days of feeding, the medial smooth muscle cells show a slight but significant increase (1.5 times the control value), and, after 7 days, so do the adventitial fibroblasts (3 x) and the endothelial cells (EC) (2 x). After 14 days LI for all three cell types is again at control values, but after 21 days (wall thickness is no increased) each cell type shows at least a fivefold increase; by 35 days all are again near control levels. In the intra-acinar region, by 14 days, "newly" muscularized arteries are identified and increase in number and proportion up to 35 days; 3H-thymidine uptake is not evident in this cell type until 35 days have passed. The ECs of these arteries, however, show a striking increase in LI after 14 days as do those of the alveolar capillaries. The ECs of the intra-acinar veins show a biphasic response being increased after 7, 28, and 35 days. The present study has shown that Crotalaria ingestion induces hyperplasia and hypertrophy of pulmonary arterial cells at pre- and intra-acinar levels. The early increase in LI probably represents a response to the original cell injury, the later changes, a response to continuing damage or, in part, adaptation to the pulmonary hypertension now present. Images Figure 3 Figure 7 PMID:7055214

Pulmonary arterial distension and vagal afferent nerve activity in anaesthetized dogs.

PubMed

Moore, Jonathan P; Hainsworth, Roger; Drinkhill, Mark J

2004-03-16

Distension of the main pulmonary artery and its bifurcation are known to result in a reflex vasoconstriction and increased respiratory drive; however, these responses are observed at abnormally high distending pressures. In this study we recorded afferent activity from pulmonary arterial baroreceptors to investigate their stimulus-response characteristics and to determine whether they are influenced by physiological changes in intrathoracic pressure. In chloralose-anaesthetized dogs, a cardiopulmonary bypass was established, the pulmonary trunk and its main branches were vascularly isolated and perfused with venous blood at pulsatile pressures designed to simulate the normal pulmonary arterial pressure waveform. Afferent slips of a cervical vagus were dissected and nerve fibres identified that displayed discharge patterns with characteristics expected from pulmonary arterial baroreceptors. Recordings were obtained with (a) chest open (b) chest closed and resealed, and (c) with phasic negative intrathoracic pressures in the resealed chest. Pressure-discharge characteristics obtained in the open-chest animals indicated that the threshold pulmonary pressure (corresponding to 5% of the overall response) was 17.1 +/- 2.9 and the inflexion point of the curve was 29.2 +/- 3.3 mmHg (mean +/-S.E.M). In closed-chest animals the threshold and inflexion pressures were reduced to 12.0 +/- 1.7 and 20.7 +/- 1.8 mmHg. Application of phasic negative intrathoracic pressures further reduced the threshold and inflexion pressures to 9.5 +/- 1.2 mmHg (P < 0.05 vs. open) and 14.7 +/- 0.8 mmHg (P < 0.003 vs. open and P < 0.02 vs. atmospheric). These results indicate that under physiological conditions, with closed-chest and phasic negative intrathoracic pressure changes similar to those associated with normal breathing, activity from pulmonary baroreceptors is obtained at physiological pulmonary arterial pressures in intact animals.

Changing demographics, epidemiology, and survival of incident pulmonary arterial hypertension: results from the pulmonary hypertension registry of the United Kingdom and Ireland.

PubMed

Ling, Yi; Johnson, Martin K; Kiely, David G; Condliffe, Robin; Elliot, Charlie A; Gibbs, J Simon R; Howard, Luke S; Pepke-Zaba, Joanna; Sheares, Karen K K; Corris, Paul A; Fisher, Andrew J; Lordan, James L; Gaine, Sean; Coghlan, J Gerry; Wort, S John; Gatzoulis, Michael A; Peacock, Andrew J

2012-10-15

Incident pulmonary arterial hypertension was underrepresented in most pulmonary hypertension registries and may have a different disease profile to prevalent disease. To determine the characteristics and outcome of a purely incident, treatment-naive cohort of idiopathic, heritable, and anorexigen-associated pulmonary arterial hypertension and to determine the changes in presentations and survival over the past decade in the United Kingdom and Ireland. All consecutive newly diagnosed patients from 2001 to 2009 were identified prospectively. A total of 482 patients (93% idiopathic, 5% heritable, and 2% anorexigen-associated pulmonary arterial hypertension) were diagnosed, giving rise to an estimated incidence of 1.1 cases per million per year and prevalence of 6.6 cases per million in 2009. Younger patients (age ≤ 50 yrs) had shorter duration of symptoms, fewer comorbidities, better functional and exercise capacity, higher percent diffusing capacity of carbon monoxide, more severe hemodynamic impairment, but better survival compared with older patients. In comparison with the earlier cohorts, patients diagnosed in 2007-2009 were older, more obese, had lower percent diffusing capacity of carbon monoxide,(,) and more comorbidities, but better survival. Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) equation, REVEAL risk score, and Pulmonary Hypertension Connection Registry survival equation accurately predicted survival of our incident cohort at 1 year. This study highlights the influence of age on phenotypes of incident pulmonary arterial hypertension and has shown the changes in demographics and epidemiology over the past decade in a national setting. The results suggest that there may be two subtypes of patients: the younger subtype with more severe hemodynamic impairment but better survival, compared with the older subtype who has more comorbidities.

Trial occlusion to assess the risk of persistent pulmonary arterial hypertension after closure of a large patent ductus arteriosus in adolescents and adults with elevated pulmonary artery pressure.

PubMed

Zhang, Duan-Zhen; Zhu, Xian-Yang; Lv, Bei; Cui, Chun-Sheng; Han, Xiu-Min; Sheng, Xiao-Tang; Wang, Qi-Guang; Zhang, Po

2014-08-01

No method is available to predict whether patients with patent ductus arteriosus (PDA) and severe pulmonary arterial hypertension (PAH) will show persistent postprocedural PAH (PP-PAH) after PDA closure. This study evaluated the usefulness of trial occlusion for predicting PP-PAH after transcatheter PDA closure in patients with severe PAH. Trial occlusion was performed in 137 patients (age ≥12 years) with PDA and severe PAH. All patients undergoing trial occlusion had a mean pulmonary artery pressure ≥45 mm Hg, pulmonary:systemic flow (Qp/Qs) ratio >1.5, and pulmonary:systemic resistance (Rp/Rs) ratio <0.7. A total of 135 patients (98%) showing stable hemodynamics during occlusion trial underwent successful device closure. Linear correlation analysis revealed weak or moderate relationships between the baseline and post-trial pulmonary artery pressures and pulmonary:systemic pressure (Pp/Ps) ratios. Patients were followed up for 1 to 10 years (median: 5 years). PP-PAH (systolic pulmonary artery pressure >50 mm Hg by Doppler echocardiography) was detected in 17 patients (13%), who displayed no significant differences in sex and age compared with patients without PP-PAH. According to discriminant analysis, the strongest discriminators between patients with and without PP-PAH were the baseline left ventricular end-diastolic volume and the baseline and post-trial systolic Pp/Ps ratios. In particular, a post-trial systolic Pp/Ps ratio >0.5 correctly classified 100% of the PP-PAH and non-PAH patients. Trial occlusion is a feasible method to predict PP-PAH in patients with PDA and severe PAH. A post-trial systolic Pp/Ps ratio >0.5 indicates a high risk of PP-PAH occurrence after device closure. © 2014 American Heart Association, Inc.

Three-Dimensional Right Ventricular Strain Versus Volume Quantification in Heart Transplant Recipients in Relation to Pulmonary Artery Pressure.

PubMed

Sade, Leyla Elif; Kozan, Hatice; Eroglu, Serpil; Pirat, Bahar; Aydinalp, Alp; Sezgin, Atilla; Muderrisoglu, Haldun

2017-02-01

Residual pulmonary hypertension challenges the right ventricular function and worsens the prognosis in heart transplant recipients. The complex geometry of the right ventricle complicates estimation of its function with conventional transthoracic echocardiography. We evaluated right ventricular function in heart transplant recipients with the use of 3-dimensional echocardiography in relation to systolic pulmonary artery pressure. We performed 32 studies in 26 heart transplant patients, with 6 patients having 2 studies at different time points with different pressures and thus included. Right atrial volume, tricuspid annular plane systolic excursion, peak systolic annular velocity, fractional area change, and 2-dimensional speckle tracking longitudinal strain were obtained by 2-dimensional and tissue Doppler imaging. Three-dimensional right ventricular volumes, ejection fraction, and 3-dimensional right ventricular strain were obtained from the 3-dimensional data set by echocardiographers. Systolic pulmonary artery pressure was obtained during right heart catheterization. Overall mean systolic pulmonary artery pressure was 26 ± 7 mm Hg (range, 14-44 mmHg). Three-dimensional end-diastolic (r = 0.75; P < .001) and end-systolic volumes (r = 0.55; P = .001)correlated well with systolic pulmonary artery pressure. Right ventricular ejection fraction and right atrium volume also significantly correlated with systolic pulmonary artery pressure (r = 0.49 and P = .01 for both). However, right ventricular 2- and 3-dimensional strain, tricuspid annular plane systolic excursion, and tricuspid annular velocity did not. The effects of pulmonary hemodynamic burden on right ventricular function are better estimated by a 3-dimensional volume evaluation than with 3-dimensional longitudinal strain and other 2-dimensional and tissue Doppler measurements. These results suggest that the peculiar anatomy of the right ventricle necessitates 3-dimensional volume quantification in heart transplant recipients in relation to residual pulmonary hypertension.

The role of disturbed blood flow in the development of pulmonary arterial hypertension: lessons from preclinical animal models.

PubMed

Dickinson, Michael G; Bartelds, Beatrijs; Borgdorff, Marinus A J; Berger, Rolf M F

2013-07-01

Pulmonary arterial hypertension (PAH) is a progressive pulmonary vasoproliferative disorder characterized by the development of unique neointimal lesions, including concentric laminar intima fibrosis and plexiform lesions. Although the histomorphology of neointimal lesions is well described, the pathogenesis of PAH and neointimal development is largely unknown. After three decades of PAH pathobiology research the focus has shifted from vasoconstriction towards a mechanism of cancer-like angioproliferation. In this concept the role of disturbed blood flow is seen as an important trigger in the development of vascular remodeling. For instance, in PAH associated with congenital heart disease, increased pulmonary blood flow (i.e., systemic-to-pulmonary shunt) is an essential trigger for the occurrence of neointimal lesions and PAH development. Still, questions remain about the exact role of these blood flow characteristics in disease progression. PAH animal models are important for obtaining insight in new pathobiological processes and therapeutical targets. However, as for any preclinical model the pathophysiological mechanism and clinical course has to be comparable to the human disease that it mimics. This means that animal models mimicking human PAH ideally are characterized by: a hit recognized in human disease (e.g., altered pulmonary blood flow), specific vascular remodeling resembling human neointimal lesions, and disease progression that leads to right ventriclular dysfunction and death. A review that underlines the current knowledge of PAH due to disturbed flow is still lacking. In this review we will summarize the current knowledge obtained from PAH animal models associated with disturbed pulmonary blood flow and address questions for future treatment strategies for PAH.

Changes in pulmonary arterial wall mechanical properties and lumenal architecture with induced vascular remodeling

NASA Astrophysics Data System (ADS)

Molthen, Robert C.; Heinrich, Amy E.; Haworth, Steven T.; Dawson, Christopher A.

2004-04-01

To explore and quantify pulmonary arterial remodeling we used various methods including micro-CT, high-resolution 3-dimensional x-ray imaging, to examine the structure and function of intact pulmonary vessels in isolated rat lungs. The rat is commonly used as an animal model for studies of pulmonary hypertension (PH) and the accompanying vascular remodeling, where vascular remodeling has been defined primarily by changes in the vessel wall composition in response to hypertension inducing stimuli such as chronic hypoxic exposure (CHE) or monocrotaline (MCT) injection. Little information has been provided as to how such changes affect the vessel wall mechanical properties or the lumenal architecture of the pulmonary arterial system that actually account for the hemodynamic consequences of the remodeling. In addition, although the link between primary forms of pulmonary hypertension and inherited genetics is well established, the role that genetic coding plays in hemodynamics and vascular remodeling is not. Therefore, we are utilizing Fawn-Hooded (FH), Sprague-Dawley (SD) and Brown Norway (BN)rat strains along with unique imaging methods to parameterize both vessel distensibility and lumenal morphometry using a principal pulmonary arterial pathway analysis based on self-consistency. We have found for the hypoxia model, in addition to decreased body weight, increased hematocrit, increased right ventricular hypertrophy, the distensibility of the pulmonary arteries is shown to decrease significantly in the presence of remodeling.

Multidetector computed tomography shows reverse cardiac remodeling after double lung transplantation for pulmonary hypertension.

PubMed

Mandich Crovetto, D; Alonso Charterina, S; Jiménez López-Guarch, C; Pont Vilalta, M; Pérez Núñez, M; de Pablo Gafas, A; Escribano Subías, P

2016-01-01

To use multidetector computed tomography (MDCT) to evaluate the structural changes in the right heart and pulmonary arteries that occur in patients with severe pulmonary hypertension treated by double lung transplantation. This was a retrospective study of 21 consecutive patients diagnosed with severe pulmonary hypertension who underwent double lung transplantation at our center between 2010 and 2014. We analyzed the last MDCT study done before lung transplantation and the first MDCT study done after lung transplantation. We recorded the following variables: diameter of the pulmonary artery trunk, ratio of the diameter of the pulmonary artery trunk to the diameter of the ascending aorta, diameter of the right ventricle, ratio of the diameter of the left ventricle to the diameter of the right ventricle, and eccentricity index. Statistical analysis consisted of the comparison of the means of the variables recorded. In all cases analyzed, the MDCT study done a mean of 24±14 days after double lung transplantation showed a significant reduction in the size of the right heart chambers, with improved indices of ventricular interdependency index, and reduction in the size of the pulmonary artery trunk (p<0.001 for all the variables analyzed). Patients with pulmonary hypertension treated by double lung transplantation present early reverse remodeling of the changes in the structures of the right heart and pulmonary arterial tree. MDCT is useful for detecting these changes. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

[Pulmonary arterial hypertension associated with human immunodeficiency virus: thirty years after its description].

PubMed

Sandoval Gutiérrez, José Luis

2018-04-11

The development of pulmonary arterial hypertension associated with human immunodeficiency virus reduces the probability of survival in the patient affected compared to those without cardiopulmonary disease. The pathophysiology is uncertain. There are several lines of research to associate the different proteins of the virus in the endothelial lesion. From a therapeutic point of view there are treatment modalities that allow an acceptable life expectancy. Copyright © 2018 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Diverse forms of pulmonary hypertension remodel the arterial tree to a high shear phenotype

PubMed Central

Allen, Roblee P.; Schelegle, Edward S.

2014-01-01

Pulmonary hypertension (PH) is associated with progressive changes in arterial network complexity. An allometric model is derived that integrates diameter branching complexity between pulmonary arterioles of generation n and the main pulmonary artery (MPA) via a power-law exponent (X) in dn = dMPA2−n/X and the arterial area ratio β = 21–2/X. Our hypothesis is that diverse forms of PH demonstrate early decrements in X independent of etiology and pathogenesis, which alters the arteriolar shear stress load from a low-shear stress (X > 2, β > 1) to a high-shear stress phenotype (X < 2, β < 1). Model assessment was accomplished by comparing theoretical predictions to retrospective morphometric and hemodynamic measurements made available from a total of 221 PH-free and PH subjects diagnosed with diverse forms (World Health Organization; WHO groups I-IV) of PH: mitral stenosis, congenital heart disease, chronic obstructive pulmonary lung disease, chronic thromboembolism, idiopathic pulmonary arterial hypertension (IPAH), familial (FPAH), collagen vascular disease, and methamphetamine exposure. X was calculated from pulmonary artery pressure (PPA), cardiac output (Q) and body weight (M), utilizing an allometric power-law prediction of X relative to a PH-free state. Comparisons of X between PAH-free and PAH subjects indicates a characteristic reduction in area that elevates arteriolar shear stress, which may contribute to mechanisms of endothelial dysfunction and injury before clinically defined thresholds of pulmonary vascular resistance and PH. We conclude that the evaluation of X may be of use in identifying reversible and irreversible phases of PH in the early course of the disease process. PMID:24858853

Identification of a Novel Hybridization from Isosorbide 5-Mononitrate and Bardoxolone Methyl with Dual Activities of Pulmonary Vasodilation and Vascular Remodeling Inhibition on Pulmonary Arterial Hypertension Rats.

PubMed

Cheng, Yusheng; Gong, Yan; Qian, Shuai; Mou, Yi; Li, Hanrui; Chen, Xijing; Kong, Hui; Xie, Weiping; Wang, Hong; Zhang, Yihua; Huang, Zhangjian

2018-02-22

Given the clinical therapeutic efficacy of oral-dosed bardoxolone methyl (1) and the selective vasodilatory effect caused by inhalation of nitric oxide (NO) on pulmonary arterial hypertension (PAH) patients, a new hybrid (CDDO-NO, 2) from 1 and NO donor isosorbide 5-mononitrate (3) was designed and synthesized. This hybrid could liberate 1 and NO in the lungs of rats after trachea injection. Significantly, 2 lowered mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP), decreased right ventricular hypertrophy (RVH), and attenuated pulmonary artery medial thickness (PAMT) and vascular muscularization in monocrotaline (MCT)-induced PAH rats. Meanwhile, 2 inhibited overproliferation of perivascular cells and diminished macrophage infiltration and oxidative stress by inactivation of NOX4. In addition, 2 markedly reduced cardiac hypertrophy and fibrosis in the PAH rats. Overall, 2 exhibited potent dual activities of pulmonary vasodilation and vascular remodeling inhibition, suggesting that it may be a promising agent for PAH intervention.

Micro-CT image-derived metrics quantify arterial wall distensibility reduction in a rat model of pulmonary hypertension

NASA Astrophysics Data System (ADS)

Johnson, Roger H.; Karau, Kelly L.; Molthen, Robert C.; Haworth, Steven T.; Dawson, Christopher A.

2000-04-01

We developed methods to quantify arterial structural and mechanical properties in excised rat lungs and applied them to investigate the distensibility decrease accompanying chronic hypoxia-induced pulmonary hypertension. Lungs of control and hypertensive (three weeks 11% O2) animals were excised and a contrast agent introduced before micro-CT imaging with a special purpose scanner. For each lung, four 3D image data sets were obtained, each at a different intra-arterial contrast agent pressure. Vessel segment diameters and lengths were measured at all levels in the arterial tree hierarchy, and these data used to generate features sensitive to distensibility changes. Results indicate that measurements obtained from 3D micro-CT images can be used to quantify vessel biomechanical properties in this rat model of pulmonary hypertension and that distensibility is reduced by exposure to chronic hypoxia. Mechanical properties can be assessed in a localized fashion and quantified in a spatially-resolved way or as a single parameter describing the tree as a whole. Micro-CT is a nondestructive way to rapidly assess structural and mechanical properties of arteries in small animal organs maintained in a physiological state. Quantitative features measured by this method may provide valuable insights into the mechanisms causing the elevated pressures in pulmonary hypertension of differing etiologies and should become increasingly valuable tools in the study of complex phenotypes in small-animal models of important diseases such as hypertension.

Colforsin-induced vasodilation in chronic hypoxic pulmonary hypertension in rats.

PubMed

Yokochi, Ayumu; Itoh, Hiroo; Maruyama, Junko; Zhang, Erquan; Jiang, Baohua; Mitani, Yoshihide; Hamada, Chikuma; Maruyama, Kazuo

2010-06-01

Colforsin, a water-soluble forskolin derivative, directly activates adenylate cyclase and thereby increases the 3',5'-cyclic adenosine monophosphate (cAMP) level in vascular smooth muscle cells. In this study, we investigated the vasodilatory action of colforsin on structurally remodeled pulmonary arteries from rats with pulmonary hypertension (PH). A total of 32 rats were subjected to hypobaric hypoxia (380 mmHg, 10% oxygen) for 10 days to induce chronic hypoxic PH, while 39 rats were kept in room air. Changes in isometric force were recorded in endothelium-intact (+E) and -denuded (-E) pulmonary arteries from the PH and control (non-PH) rats. Colforsin-induced vasodilation was impaired in both +E and -E arteries from PH rats compared with their respective controls. Endothelial removal did not influence colforsin-induced vasodilation in the arteries from control rats, but attenuated it in arteries from PH rats. The inhibition of nitric oxide (NO) synthase did not influence colforsin-induced vasodilation in +E arteries from controls, but attenuated it in +E arteries from PH rats, shifting its concentration-response curve closer to that of -E arteries from PH rats. Vasodilation induced by 8-bromo-cAMP (a cell-permeable cAMP analog) was also impaired in -E arteries from PH rats, but not in +E arteries from PH rats, compared with their respective controls. cAMP-mediated vasodilatory responses without beta-adrenergic receptor activation are impaired in structurally remodeled pulmonary arteries from PH rats. In these arteries, endothelial cells presumably play a compensatory role against the impaired cAMP-mediated vasodilatory response by releasing NO (and thereby attenuating the impairment). The results suggest that colforsin could be effective in the treatment of PH.

Repair of a Large Main Pulmonary Artery Aneurysm in a 71-Year-Old Jehovah's Witness Patient

PubMed Central

Henn, Lucas W.; Esmailian, Fardad

2013-01-01

Pulmonary artery aneurysm is a rarely reported and poorly studied entity; most mentions in the literature are in case series and case reports. Cardiac surgery in Jehovah's Witness patients is occurring more frequently because of improved techniques of blood conservation. We report the repair of a large pulmonary artery aneurysm in a 71-year-old woman who was a Jehovah's Witness. Using total cardiopulmonary bypass, we replaced the main pulmonary artery and both branches with Gelweave tube-grafts, because the fragility of a homograft presented possible bleeding problems. The patient recovered rapidly, and her symptoms were greatly improved. We think that a patient's status as a Jehovah's Witness need not preclude potentially life-saving cardiac operations. PMID:23914038

Repair of a large main pulmonary artery aneurysm in a 71-year-old Jehovah's Witness patient.

PubMed

Henn, Lucas W; Esmailian, Fardad

2013-01-01

Pulmonary artery aneurysm is a rarely reported and poorly studied entity; most mentions in the literature are in case series and case reports. Cardiac surgery in Jehovah's Witness patients is occurring more frequently because of improved techniques of blood conservation. We report the repair of a large pulmonary artery aneurysm in a 71-year-old woman who was a Jehovah's Witness. Using total cardiopulmonary bypass, we replaced the main pulmonary artery and both branches with Gelweave tube-grafts, because the fragility of a homograft presented possible bleeding problems. The patient recovered rapidly, and her symptoms were greatly improved. We think that a patient's status as a Jehovah's Witness need not preclude potentially life-saving cardiac operations.

Primary extraskeletal myxoid chondrosarcoma of pulmonary arteries: a rare mimic of acute pulmonary thromboembolism.

PubMed

Gadabanahalli, Karthik; Belaval, Vinay V; Bhat, Venkatraman; Gorur, Imran M

2015-04-01

Primary extraskeletal myxoid chondrosarcoma of the pulmonary arteries is a very rare entity. Multimodality imaging reports on this entity are few. Myxoid chondrosarcoma is characterized by chondroid and neurogenic differentiation in extraskeletal locations. These tumours represent fewer than 2.5% of all soft-tissue sarcomas, and are most commonly found in the lower extremities, limb girdles, distal extremities and trunk. We report an unusual case of a 31-year old man with histopathologically proven extraskeletal myxoid chondrosarcoma of the pulmonary arteries mimicking acute pulmonary thromboembolism. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Unusual Survival of Anomalous Left Coronary Artery From the Pulmonary Artery With Severe Rheumatic Mitral Stenosis in Septuagenarian Women: Foes Becoming Friends?

PubMed

Sinha, Santosh Kumar; Khanra, Dibbendhu; Jha, Mukesh Jitendra; Singh, Karandeep; Razi, Mahamdulla; Goel, Amit; Mishra, Vikas; Asif, Mohammad; Sachan, Mohit; Afdaali, Nasar; Kumar, Ashutosh; Thakur, Ramesh; Krishna, Vinay; Pandey, Umeshwar; Varma, Chandra Mohan

2016-10-01

ALCAPA syndrome (anomalous origin of the left coronary artery from the pulmonary artery) is a rare disease but lethal with clinical expression from myocardial infarction, congestive heart failure to death during early infancy and unusual survival to adulthood. We report a 73-year-old woman with ALCAPA who presented with exertional dyspnea (NYHA functional class II) over past 2 years. Physical examination revealed soft S, long mid diastolic rumbling murmur and apical pan-systolic murmur. Electrocardiography displayed biatrial enlargement and poor R progression and normal sinus rhythm. Echocardiography established calcified severe mitral stenosis (MS), presence of continuous flow entering the pulmonary trunk, turbulent continuous flow in inter-ventricular septum with left to right shunt in contrast echocardiography and normal systolic function. Coronary angiogram showed absence of left coronary artery (LCA) originating from aorta, dilated and tortuous right coronary artery (RCA) and abundant Rentrop grade 3 intercoronary collateral communicating with LCA originating from pulmonary trunk which was also confirmed on coronary CT angiogram thus establishing diagnosis of ALCAPA. It is exceedingly rare to be associated with severe MS. However, such a long survival in our patient can be explained by the severe pulmonary arterial hypertension which may be contributing to lesser coronary steal.

PCPA protects against monocrotaline-induced pulmonary arterial remodeling in rats: potential roles of connective tissue growth factor.

PubMed

Bai, Yang; Li, Zhong-Xia; Zhao, Yue-Tong; Liu, Mo; Wang, Yun; Lian, Guo-Chao; Zhao, Qi; Wang, Huai-Liang

2017-12-19

The purpose of this study was to investigate the mechanism of monocrotaline (MCT)-induced pulmonary artery hypertension (PAH) and determine whether 4-chloro-DL-phenylalanine (PCPA) could inhibit pulmonary arterial remodeling associated with connective tissue growth factor (CTGF) expression and downstream signal pathway. MCT was administered to forty Sprague Dawley rats to establish the PAH model. PCPA was administered at doses of 50 and 100 mg/kg once daily for 3 weeks via intraperitoneal injection. On day 22, the pulmonary arterial pressure (PAP), right ventricle hypertrophy index (RVI) and pulmonary artery morphology were assessed and the serotonin receptor-1B (SR-1B), CTGF, p-ERK/ERK were measured by western blot or immunohistochemistry. The concentration of serotonin in plasma was checked by ELISA. Apoptosis and apoptosis-related indexes were detected by TUNEL and western blot. In the MCT-induced PAH models, the PAP, RVI, pulmonary vascular remodeling, SR-1B index, CTGF index, anti-apoptotic factors bcl-xl and bcl-2, serotonin concentration in plasma were all increased and the pro-apoptotic factor caspase-3 was reduced. PCPA significantly ameliorated pulmonary arterial remodeling induced by MCT, and this action was associated with accelerated apoptosis and down-regulation of CTGF, SR-1B and p-ERK/ERK. The present study suggests that PCPA protects against the pathogenesis of PAH by suppressing remodeling and inducing apoptosis, which are likely associated with CTGF and downstream ERK signaling pathway in rats.

History of Right Heart Catheterization: 100 Years of Experimentation and Methodology Development

PubMed Central

Nossaman, Bobby D.; Scruggs, Brittni A.; Nossaman, Vaughn E.; Murthy, Subramanyam N.; Kadowitz, Philip J.

2010-01-01

The development of right heart catheterization has provided the clinician the ability to diagnose patients with congenital and acquired right heart disease, and to monitor patients in the ICU with significant cardiovascular illnesses. The development of bedside pulmonary artery catheterization has become a standard of care for the critically ill patient since its introduction into the ICU almost 40 years ago. However, adoption of this procedure into the mainstream of clinical practice occurred without prior evaluation or demonstration of its clinical or cost-effectiveness. Moreover, current randomized, controlled trials provide little evidence in support of the clinical utility of pulmonary artery catheterization in the management of critically ill patients. Nevertheless, the right heart catheter is an important diagnostic tool to assist the clinician in the diagnosis of congenital heart disease and acquired right heart disease, and moreover, when catheter placement is proximal to the right auricle (atria), this catheter provides an important and safe route for administration of fluids, medications, and parenteral nutrition. The purpose of this manuscript is to review the development of right heart catheterization that led to the ability to conduct physiologic studies in cardiovascular dynamics in normal individuals and in patients with cardiovascular diseases, and to review current controversies of the extension of the right heart catheter, the pulmonary artery catheter. PMID:20160536

Afferent fibres from pulmonary arterial baroreceptors in the left cardiac sympathetic nerve of the cat

PubMed Central

Nishi, K.; Sakanashi, M.; Takenaka, F.

1974-01-01

1. Afferent discharges were recorded from the left cardiac sympathetic nerve or the third sympathetic ramus communicans of anaesthetized cats. Twenty-one single units with baroreceptor activity were obtained. 2. The receptors of each unit were localized to the extrapulmonary part of the pulmonary artery, determined by direct mechanical probing of the wall of the pulmonary artery after death of the animals. Conduction velocity of the fibres ranged from 2·5 to 15·7 m/sec. 3. Afferent discharges occurred irregularly under artificial ventilation. The impulse activity was increased when pulmonary arterial pressure was raised by an intravenous infusion of Locke solution, or by occlusion of lung roots, and decreased by bleeding the animal from the femoral artery. 4. Above a threshold pressure, discharges occurred synchronously with the systolic pressure pulse in the pulmonary artery. A progressive further rise in pressure did not produce an increase in the number of impulses per heart beat. Occlusion of lung roots initially elicited a burst of discharges but the number of impulses for each cardiac cycle gradually decreased. 5. The receptors responded to repetitive mechanical stimuli up to a frequency of 10/sec, but failed to respond to stimuli delivered at 20/sec. 6. The results provide further evidence for the presence of afferent fibres in the cardiac sympathetic nerve. These afferent fibres are likely to provide the spinal cord with specific information only on transient changes in pulmonary arterial pressure. PMID:4850456

Teaching Pulmonary Gas Exchange Physiology Using Computer Modeling

ERIC Educational Resources Information Center

Kapitan, Kent S.

2008-01-01

Students often have difficulty understanding the relationship of O[subscript 2] consumption, CO[subscript 2] production, cardiac output, and distribution of ventilation-perfusion ratios in the lung to the final arterial blood gas composition. To overcome this difficulty, I have developed an interactive computer simulation of pulmonary gas exchange…

Primary cardiac malignant fibrous histiocytoma in the right ventricular infundibulum treated with a cavo-pulmonary shunt and coronary embolization.

PubMed

Owa, M; Higashikata, T; Shimada, H; Kitahara, H; Asano, M; Nakayama, J; Hikita, H; Koyama, J; Sakurai, S; Ikeda, S

2000-12-01

A 51-year-old woman presented with progressive right ventricular infundibular wall thickening and outflow obstruction. She had had an aorto-coronary bypass for left main coronary artery disease 1 year after radiation therapy for left mammary cancer. Enhanced computed tomography showed a mass in the right ventricular free wall with no connection to the mediastinum; the tumor extended into the main pulmonary artery, but there was no other evidence of a primary or metastatic tumor. A biopsy specimen was obtained and based on the microscopic and immuno-histochemical findings (vimentin and Kp-1 positive) the diagnosis was primary cardiac malignant fibrous histiocytoma, which is very rare. A cavo-pulmonary artery connection lessened her symptoms, but embolization of the coronary artery to try and to reduce the mass had minimal effect. Four months after the tumor was diagnosed she died of extended pulmonary artery obstruction.

Anomalous origin of the left coronary artery from the pulmonary artery with patent ductus arteriosus: a must to recognize entity.

PubMed

Awasthy, Neeraj; Marwah, Ashutosh; Sharma, Rajesh; Dalvi, Bharat

2010-09-01

Anomalous left coronary artery from the pulmonary trunk (ALCAPA) presents in early infancy with a clinical picture of congestive heart failure with left ventricular (LV) dysfunction and mitral insufficiency. These manifestations of myocardial ischaemia may be masked in the presence of an associated patent ductus arteriosus (PDA) or ventricular septal defect (VSD) which prevents the fall of pulmonary artery pressures and allows perfusion of the anomalous coronary artery. We present a case of a patient with large PDA-associated ALCAPA and preserved LV function. The importance of such a finding lies in the fact that VSD closure or PDA ligation in such cases would unmask the ALCAPA.

Systemic Artery to Pulmonary Vein Fistula After Right Upper Lobectomy Demonstrated by 4-Dimensional Flow Magnetic Resonance Imaging.

PubMed

Legras, Antoine; Azarine, Arshid; Poitier, Bastien; Messas, Emmanuel; Le Pimpec-Barthes, Françoise

2017-08-01

Postoperative systemic artery to pulmonary vein fistula is very rare. In this report, we describe an exceptional condition of both intrapulmonary arteriovenous fistula and systemic artery to pulmonary vein fistula, involving all right hemithoracic systemic arteries, inducing left-to-left shunt. This condition was responsible for heart failure, 24 years after a right upper lobectomy for inflammatory tumor. Investigations included computed tomographic angiography, arteriography, and four-dimensional flow magnetic resonance imaging. Differential diagnosis and management are discussed. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

In Situ Fracture of Stents Implanted for Relief of Pulmonary Arterial Stenosis in Patients with Congenitally Malformed Hearts

PubMed Central

McElhinney, Doff B.; Bergersen, Lisa; Marshall, Audrey C.

2014-01-01

Background One of the most common uses of stents in patients with congenitally malformed hearts is treatment of pulmonary arterial stenosis. Although there are reports of fractured pulmonary arterial stents, little is known about the risk factors for, and implications of, such fractures. Methods We reviewed angiograms to identify fractures in stents previously inserted to relieve stenoses in pulmonary arteries from 1990 through 2001 in patients who also underwent follow-up catheterization at least 3 years after placement of the stent. We undertook matched cohort analysis, matching a ratio of 2 fractured to 1 unfractured stent. Results Overall, 166 stents meeting the criterions of our study had been placed in 120 patients. We identified fractures in 35 stents (21%) in 29 patients. All fractured stents were in the central pulmonary arteries, 24 (69%) in the central part of the right pulmonary artery, and all were complete axial fractures, or complex fractures along at least 2 planes. Stent-related factors associated with increased risk of fracture identified by multivariable logistic regression included placement in close apposition to the ascending aorta (p = 0.001), and a larger expanded diameter (p = 0.002). There was obstruction across 28 of 35 fractured stents, which was severe in 11. We re-stented 21 of the fractured stents, and recurrent fracture was later diagnosed in 3 of these. A fragment of the fractured stent embolized distally in 2 patients, without clinically important effects. Conclusions In situ fracture of pulmonary arterial stents is relatively common, and in most cases is related to compression by the aorta. There is usually recurrent obstruction across the fractured stent, but fractured stents rarely embolize, and are not associated with other significant complications. PMID:18559137

Arterial morphology responds differently to Captopril then N-acetylcysteine in a monocrotaline rat model of pulmonary hypertension

NASA Astrophysics Data System (ADS)

Molthen, Robert; Wu, Qingping; Baumgardt, Shelley; Kohlhepp, Laura; Shingrani, Rahul; Krenz, Gary

2010-03-01

Pulmonary hypertension (PH) is an incurable condition inevitably resulting in death because of increased right heart workload and eventual failure. PH causes pulmonary vascular remodeling, including muscularization of the arteries, and a reduction in the typically large vascular compliance of the pulmonary circulation. We used a rat model of monocrotaline (MCT) induced PH to evaluated and compared Captopril (an angiotensin converting enzyme inhibitor with antioxidant capacity) and N-acetylcysteine (NAC, a mucolytic with a large antioxidant capacity) as possible treatments. Twenty-eight days after MCT injection, the rats were sacrificed and heart, blood, and lungs were studied to measure indices such as right ventricular hypertrophy (RVH), hematocrit, pulmonary vascular resistance (PVR), vessel morphology and biomechanics. We implemented microfocal X-ray computed tomography to image the pulmonary arterial tree at intravascular pressures of 30, 21, 12, and 6 mmHg and then used automated vessel detection and measurement algorithms to perform morphological analysis and estimate the distensibility of the arterial tree. The vessel detection and measurement algorithms quickly and effectively mapped and measured the vascular trees at each intravascular pressure. Monocrotaline treatment, and the ensuing PH, resulted in a significantly decreased arterial distensibility, increased PVR, and tended to decrease the length of the main pulmonary trunk. In rats with PH induced by monocrotaline, Captopril treatment significantly increased arterial distensibility and decrease PVR. NAC treatment did not result in an improvement, it did not significantly increase distensibility and resulted in further increase in PVR. Interestingly, NAC tended to increase peripheral vascular density. The results suggest that arterial distensibility may be more important than distal collateral pathways in maintaining PVR at normally low values.

Interleukin 13– and interleukin 17A–induced pulmonary hypertension phenotype due to inhalation of antigen and fine particles from air pollution

PubMed Central

Park, Sung-Hyun; Chen, Wen-Chi; Esmaeil, Nafiseh; Lucas, Benjamin; Marsh, Leigh M.; Reibman, Joan

2014-01-01

Abstract Pulmonary hypertension has a marked detrimental effect on quality of life and life expectancy. In a mouse model of antigen-induced pulmonary arterial remodeling, we have recently shown that coexposure to urban ambient particulate matter (PM) significantly increased the thickening of the pulmonary arteries and also resulted in significantly increased right ventricular systolic pressures. Here we interrogate the mechanism and show that combined neutralization of interleukin 13 (IL-13) and IL-17A significantly ameliorated the increase in right ventricular systolic pressure, the circumferential muscularization of pulmonary arteries, and the molecular change in the right ventricle. Surprisingly, our data revealed a protective role of IL-17A for the antigen- and PM-induced severe thickening of pulmonary arteries. This protection was due to the inhibition of the effects of IL-13, which drove this response, and the expression of metalloelastase and resistin-like molecule α. However, the latter was redundant for the arterial thickening response. Anti-IL-13 exacerbated airway neutrophilia, which was due to a resulting excess effect of IL-17A, confirming concurrent cross inhibition of IL-13- and IL-17A-dependent responses in the lungs of animals exposed to antigen and PM. Our experiments also identified IL-13/IL-17A-independent molecular reprogramming in the lungs induced by exposure to antigen and PM, which indicates a risk for arterial remodeling and protection from arterial constriction. Our study points to IL-13- and IL-17A-coinduced inflammation as a new template for biomarkers and therapeutic targeting for the management of immune response–induced pulmonary hypertension. PMID:25610601

Outcomes of Percutaneous Closure of Patent Ductus Arteriosus Accompanied With Unilateral Absence of Pulmonary Artery.

PubMed

Yang, Yankun; Zheng, Hong; Xu, Zhongying; Zhang, Gejun; Jin, Jinglin; Hu, Haibo; Tian, Tao; Zhou, Xianliang

2017-04-01

Limited data have reported the outcomes of percutaneous closure of patent ductus arteriosus (PDA) in patients with unilateral absence of pulmonary artery (UAPA). This study aimed to evaluate the symptomatology, diagnosis and therapy, especially the transcatheter closure of PDA in patients with PDA associated with UAPA. Patients diagnosed with PDA and UAPA were retrospectively enrolled from August 2010 through January 2016. Clinical data, treatment and follow-up information were evaluated. Thirteen patients (6 males and 7 females) were diagnosed with PDA associated with UAPA. Percutaneous closure was successfully conducted in 6 patients successfully. The median age was 7 years (7 months to 37 years). The mean diameter of the PDA and occluders were 4.7 ± 1.8mm (2-7mm) and 11.3 ± 3.9mm (6-14mm), respectively. The mean pulmonary artery pressure was 41.5 ± 13.5mmHg (25-62mmHg). The diameter of PDA has no relationship with the degree of pulmonary artery pressure (r = 0.239, P = 0.648). In 4 patients, systolic pulmonary arterial pressure decreased significantly after closure with 69.0 ± 10.7 versus 48.0 ± 11.3mmHg (P = 0.146), and also the mean pulmonary arterial pressure was 54.5 ± 5.7 mm Hg versus 30.5 ± 3.9mmHg (P = 0.04). In all, 1 patient had a trace residual shunt, which disappeared within 24 hours. In appropriate patients with PDA associated with UAPA, transcatheter closure of PDA has the potential to improve the pulmonary artery hypertension. Further follow-up is required to monitor the long-term outcomes. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Coronary artery to pulmonary artery fistula.

PubMed

Dadkhah-Tirani, Heidar; Salari, Arsalan; Shafighnia, Shora; Hosseini, Seyed Fazel; Naghdipoor, Misa

2013-01-01

Male, 69 FINAL DIAGNOSIS: Coronary artery to pulmonary artery fistula Symptoms: Chest pain Medication: - Clinical Procedure: Echocardiography • angiography • surgical intervention Specialty: Cardiology • Cardiac Surgery. Rare disease. A coronary artery fistula is an abnormal communication between a coronary artery and one of the cardiac chambers or a great vessel, so bypassing the myocardial capillary network. They are usually discovered incidentally upon coronary angiography. Clinical manifestations are variable depending on the type of fistula, the severity of shunt, site of shunt, and presence of other cardiac condition. We report a 69-year-old man without any previous medical history, who was admitted to our hospital with chest pain. The electrocardiogram (ECG) showed a sinus rhythm with ST depression in V2 to V6 precordial leads. Coronary angiography revealed a coronary artery fistula from left anterior descending coronary artery (LAD) to the main pulmonary artery, right coronary artery blockage and significant stenoses on the LAD and left circumflex artery (LCX). Surgical treatment was chosen because of the total occlusion of the right coronary artery and to relieve of pain to improve quality of life.

Adenosine monophosphate-activated protein kinase is required for pulmonary artery smooth muscle cell survival and the development of hypoxic pulmonary hypertension.

PubMed

Ibe, Joyce Christina F; Zhou, Qiyuan; Chen, Tianji; Tang, Haiyang; Yuan, Jason X-J; Raj, J Usha; Zhou, Guofei

2013-10-01

Human pulmonary artery smooth muscle cells (HPASMCs) express both adenosine monophosphate-activated protein kinase (AMPK) α1 and α2. We investigated the distinct roles of AMPK α1 and α2 in the survival of HPASMCs during hypoxia and hypoxia-induced pulmonary hypertension (PH). The exposure of HPASMCs to hypoxia (3% O2) increased AMPK activation and phosphorylation, and the inhibition of AMPK with Compound C during hypoxia decreased their viability and increased lactate dehydrogenase activity and apoptosis. Although the suppression of either AMPK α1 or α2 expression led to increased cell death, the suppression of AMPK α2 alone increased caspase-3 activity and apoptosis in HPASMCs exposed to hypoxia. It also resulted in the decreased expression of myeloid cell leukemia sequence 1 (MCL-1). The knockdown of MCL-1 or MCL-1 inhibitors increased caspase-3 activity and apoptosis in HPASMCs exposed to hypoxia. On the other hand, the suppression of AMPK α1 expression alone prevented hypoxia-mediated autophagy. The inhibition of autophagy induced cell death in HPASMCs. Our results suggest that AMPK α1 and AMPK α2 play differential roles in the survival of HPASMCs during hypoxia. The activation of AMPK α2 maintains the expression of MCL-1 and prevents apoptosis, whereas the activation of AMPK α1 stimulates autophagy, promoting HPASMC survival. Moreover, treatment with Compound C, which inhibits both isoforms of AMPK, prevented and partly reversed hypoxia-induced PH in mice. Taking these results together, our study suggests that AMPK plays a key role in the pathogenesis of pulmonary arterial hypertension, and AMPK may represent a novel therapeutic target for the treatment of pulmonary arterial hypertension.

Adenosine Monophosphate–Activated Protein Kinase Is Required for Pulmonary Artery Smooth Muscle Cell Survival and the Development of Hypoxic Pulmonary Hypertension

PubMed Central

Ibe, Joyce Christina F.; Zhou, Qiyuan; Chen, Tianji; Tang, Haiyang; Yuan, Jason X.-J.; Raj, J. Usha

2013-01-01

Human pulmonary artery smooth muscle cells (HPASMCs) express both adenosine monophosphate–activated protein kinase (AMPK) α1 and α2. We investigated the distinct roles of AMPK α1 and α2 in the survival of HPASMCs during hypoxia and hypoxia-induced pulmonary hypertension (PH). The exposure of HPASMCs to hypoxia (3% O2) increased AMPK activation and phosphorylation, and the inhibition of AMPK with Compound C during hypoxia decreased their viability and increased lactate dehydrogenase activity and apoptosis. Although the suppression of either AMPK α1 or α2 expression led to increased cell death, the suppression of AMPK α2 alone increased caspase-3 activity and apoptosis in HPASMCs exposed to hypoxia. It also resulted in the decreased expression of myeloid cell leukemia sequence 1 (MCL-1). The knockdown of MCL-1 or MCL-1 inhibitors increased caspase-3 activity and apoptosis in HPASMCs exposed to hypoxia. On the other hand, the suppression of AMPK α1 expression alone prevented hypoxia-mediated autophagy. The inhibition of autophagy induced cell death in HPASMCs. Our results suggest that AMPK α1 and AMPK α2 play differential roles in the survival of HPASMCs during hypoxia. The activation of AMPK α2 maintains the expression of MCL-1 and prevents apoptosis, whereas the activation of AMPK α1 stimulates autophagy, promoting HPASMC survival. Moreover, treatment with Compound C, which inhibits both isoforms of AMPK, prevented and partly reversed hypoxia-induced PH in mice. Taking these results together, our study suggests that AMPK plays a key role in the pathogenesis of pulmonary arterial hypertension, and AMPK may represent a novel therapeutic target for the treatment of pulmonary arterial hypertension. PMID:23668615

Pediatric Perioperative Pulmonary Arterial Hypertension: A Case-Based Primer

PubMed Central

Shah, Shilpa; Szmuszkovicz, Jacqueline R.

2017-01-01

The perioperative period is an extremely tenuous time for the pediatric patient with pulmonary arterial hypertension. This article will discuss a multidisciplinary approach to preoperative planning, the importance of early identification of pulmonary hypertensive crises, and practical strategies for postoperative management for this unique group of children. PMID:29064445

Milrinone, dobutamine or epinephrine use in asphyxiated newborn pigs resuscitated with 100% oxygen.

PubMed

Joynt, Chloë; Bigam, David L; Charrois, Gregory; Jewell, Laurence D; Korbutt, Gregory; Cheung, Po-Yin

2010-06-01

After resuscitation, asphyxiated neonates often develop poor cardiac function with hypotension, pulmonary hypertension and multiorgan ischemia. In a swine model of neonatal hypoxia-reoxygenation, effects of epinephrine, dobutamine and milrinone on systemic, pulmonary and regional hemodynamics and oxygen transport were compared. Controlled, block-randomized study. University research laboratory. Mixed breed piglets (1-3 days, 1.5-2.3 kg). In acutely instrumented piglets, normocapnic alveolar hypoxia (10-15% oxygen) was induced for 2 h followed by reoxygenation with 100% oxygen (1 h) then 21% oxygen (3 h). At 2 h of reoxygenation, after volume loading (Ringer's lactate 10 ml/kg), either saline (placebo), epinephrine (0.5 microg/kg/min), dobutamine (20 microg/kg/min) or milrinone (0.75 microg/kg/min) were infused for 2 h in a blinded, block-randomized fashion (n = 6/group). All medications similarly improved cardiac output, stroke volume and systemic oxygen delivery (vs. placebo-controls, p < 0.05). Epinephrine and dobutamine significantly increased, while milrinone maintained, mean arterial pressure over pretreatment values while placebo-treated piglets developed hypotension and shock. The mean arterial to pulmonary arterial pressures ratio was not different among groups. All medications significantly increased carotid and intestinal, but not renal, arterial blood flows and oxygen delivery, whereas milrinone caused lower renal vascular resistance than epinephrine and dobutamine-treated groups. Plasma troponin I, plasma and myocardial lactate levels, and histologic ischemic features were not different among groups. In newborn piglets with hypoxia-reoxygenation, epinephrine, dobutamine and milrinone are effective inotropes to improve cardiac output, carotid and intestinal perfusion, without aggravating pulmonary hypertension. Milrinone may also improve renal perfusion.

Inflammatory Response Mechanisms Exacerbating Hypoxemia in Coexistent Pulmonary Fibrosis and Sleep Apnea

PubMed Central

Balachandran, Jay

2015-01-01

Mediators of inflammation, oxidative stress, and chemoattractants drive the hypoxemic mechanisms that accompany pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis commonly have obstructive sleep apnea, which potentiates the hypoxic stimuli for oxidative stress, culminating in systemic inflammation and generalized vascular endothelial damage. Comorbidities like pulmonary hypertension, obesity, gastroesophageal reflux disease, and hypoxic pulmonary vasoconstriction contribute to chronic hypoxemia leading to the release of proinflammatory cytokines that may propagate clinical deterioration and alter the pulmonary fibrotic pathway. Tissue inhibitor of metalloproteinase (TIMP-1), interleukin- (IL-) 1α, cytokine-induced neutrophil chemoattractant (CINC-1, CINC-2α/β), lipopolysaccharide induced CXC chemokine (LIX), monokine induced by gamma interferon (MIG-1), macrophage inflammatory protein- (MIP-) 1α, MIP-3α, and nuclear factor- (NF-) κB appear to mediate disease progression. Adipocytes may induce hypoxia inducible factor (HIF) 1α production; GERD is associated with increased levels of lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and tumor necrosis factor alpha (TNF-α); pulmonary artery myocytes often exhibit increased cytosolic free Ca2+. Protein kinase C (PKC) mediated upregulation of TNF-α and IL-1β also occurs in the pulmonary arteries. Increased understanding of the inflammatory mechanisms driving hypoxemia in pulmonary fibrosis and obstructive sleep apnea may potentiate the identification of appropriate therapeutic targets for developing effective therapies. PMID:25944985

AMD3100 treatment attenuates pulmonary angiogenesis by reducing the c-kit (+) cells and its pro-angiogenic activity in CBDL rat lungs.

PubMed

Shen, Cheng-Cheng; Chen, Bing; Gu, Jian-Teng; Ning, Jiao-Lin; Zeng, Jing; Yi, Bin; Lu, Kai-Zhi

2018-03-01

Recent studies have shown that pulmonary angiogenesis is an important pathological process in the development of hepatopulmonary syndrome (HPS), and growing evidence has indicated that Stromal cell-derived factor 1/C-X-C chemokine receptor type 4 (SDF-1/CXCR4) axis is involved in pulmonary vascular disease by mediating the accumulation of c-kit+ cells. This study aimed to test the effect of AMD3100, an antagonist of CXCR4, in HPS pulmonary angiogenesis. Common bile duct ligation (CBDL) rats were used as experimental HPS model and were treated with AMD3100 (1.25mg/kg/day, i.p.) or 0.9% saline for 3weeks. The sham rats underwent common bile duct exposure without ligation. The c-kit+ cells accounts and its angiogenic-related functions, prosurvival signals, pulmonary angiogenesis and arterial oxygenation were analysed in these groups. Our results showed that pulmonary SDF-1/CXCR4, Akt, Erk and VEGF/VEGFR2 were significantly activated in CBDL rats, and the numbers of circulating and pulmonary c-kit+ cells were increased in CBDL rats compared with control rats. Additionally, the angiogenic-related functions of c-kit+ cells and pulmonary microvessel counts were also elevated in CBDL rats. CXCR4 inhibition reduced pulmonary c-kit+ cells and microvessel counts and improved arterial oxygenation within 3weeks in CBDL rats. The pulmonary prosurvival signals and pro-angiogenic activity of c-kit+ cells were also down-regulated in AMD3100-treated rats. In conclusion, AMD3100 treatment attenuated pulmonary angiogenesis in CBDL rats and prevented the development of HPS via reductions in pulmonary c-kit+ cells and inhibition of the prosurvival signals. Our study provides new insights in HPS treatment. Copyright © 2017. Published by Elsevier B.V.

Transcatheter closure of patent ductus arteriosus with severe pulmonary arterial hypertension in adults.

PubMed

Yan, C; Zhao, S; Jiang, S; Xu, Z; Huang, L; Zheng, H; Ling, J; Wang, C; Wu, W; Hu, H; Zhang, G; Ye, Z; Wang, H

2007-04-01

Surgical closure of patent ductus arteriosus (PDA) with severe pulmonary arterial hypertension in adults carries higher risk than in children. To investigate the application of self-expandable occluders for transcatheter closure of PDA associated with severe pulmonary arterial hypertension in adults, and the assessment of immediate and short-term results. 29 adult patients (6 men, 23 women) underwent attempted transcatheter closure of PDA at a mean (standard deviation (SD)) age of 31.1 (11.4) years (range 18-58 years) and a mean (SD) weight of 54.1 (7.1) kg (range 42-71 kg). On the basis of haemodynamic and clinical data obtained before and after trial occlusion, the final duct occlusion was determined and carried out. Radiographs of the chest, electrocardiograms and echocardiograms were used for follow-up evaluation of the treatment within 1 day, 1 month and 3-6 months after successful closure. 20 of the 29 patients had successful occlusion (group 1), and 9 patients failed (named group 2). In group 1, in which occlusion was successful, mean (SD) pulmonary arterial pressures decreased markedly after trial occlusion: 78 (19.3) mm Hg (range 50-125 mm Hg) before occlusion and 41 (13.8) mm Hg (range 23-77 mm Hg) after occlusion. Systemic arterial oxygen saturation was found to be >90% in 19 patients and <90% in the remaining patient before inhalation of oxygen, and >95% during inhalation of oxygen or after occlusion in all 20 patients. In group 2, the occlusion was not successful, because in two patients the device was not available; another two patients showed worsening of symptoms. The other five patients showed increased pulmonary arterial pressures after trial closure; their mean (SD) pulmonary arterial pressures increased by 10.3 (6) mm Hg (4-16 mm Hg) after trial occlusion, and systemic arterial oxygen saturation was 85.5% (2.6%) (range 82.6-88%) before inhalation of oxygen and 94.7% (1.7%) (range 90.7-99.1%) during inhalation of oxygen. In group 1, the dimensions of the left atrium, left ventricle and pulmonary artery increased considerably in 3-6-months of follow-up compared with those of preocclusion. Transcatheter closure is an effective treatment for adults with PDA associated with reversible severe pulmonary arterial hypertension. Further research is needed for the evaluation of long-term results.

Aortic Implantation of Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery: Long-Term Outcomes.

PubMed

Mongé, Michael C; Eltayeb, Osama; Costello, John M; Sarwark, Anne E; Carr, Michael R; Backer, Carl L

2015-07-01

Since 1989 all patients with anomalous origin of the left coronary artery from the pulmonary artery at our institution have been treated with aortic implantation. The purpose of this review was to assess the late outcomes of these patients, especially regarding left ventricular (LV) function and mitral valve insufficiency. Between 1989 and 2014, 36 patients had aortic implantation of anomalous origin of the left coronary artery from the pulmonary artery. Mean age at surgery was 2.5 ± 5.1 years (median, 0.5 years). Operative strategy included antegrade cold-blood cardioplegia, main pulmonary artery transection, aortic implantation with a large button of pulmonary artery, pulmonary reconstruction with fresh autologous pericardium, and prolonged postoperative inotropic and ventilator support. Mitral regurgitation and LV dysfunction were graded as 0 to 4 (0 = none, 1 = trivial, 1.5 = trivial-mild, 2 = mild, 2.5 = mild-moderate, 3 = moderate, 3.5 = moderate-severe, and 4 = severe). Mean mitral regurgitation grade preoperatively was 2.95 ± 0.95. Mean LV dysfunction grade was 3.14 ± 1.27. Mean cross-clamp and cardiopulmonary bypass times were 49.1 ± 18 minutes (median, 48.5 minutes) and 147.5 ± 45 minutes (median, 139 minutes), respectively. There was no operative or late mortality. Four patients had delayed sternal closure. Mean duration of ventilator support was 11 ± 6.6 days (median, 9 days). Two patients required 3 and 6 days of postoperative extracorporeal mechanical circulatory support. Mean length of stay was 25 ± 18 days (median, 19 days). No patient has required reoperation for supravalvar pulmonary stenosis, coronary stenosis, or mitral valve repair or replacement. Late echocardiographic follow-up shows a mean mitral regurgitation grade of 1.67 ± 1.05 and a mean LV dysfunction grade of 0.23 ± 0.68. Aortic implantation is our procedure of choice for patients with anomalous origin of the left coronary artery from the pulmonary artery. No patient required mitral valve repair or transplant. There was marked improvement of mitral regurgitation grade, return to essentially normal LV function, and no mortality during a 25-year period. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Use of a Doppler pulmonary artery catheter for continuous measurement of right ventricular pump function and contractility during single lung transplantation.

PubMed

Heerdt, P M; Pond, C G; Kussman, M K; Triantafillou, A N

1993-01-01

Despite numerous technologic advances in intraoperative monitoring, the only methods routinely available for assessment of right ventricular function in lung transplant recipients are continuous measurement of right heart pressures and intermittent thermodilution determination of cardiac output and ejection fraction. Additional data may now be obtained with transesophageal echocardiography, although this technology is expensive and not widely available and requires diverting attention from a potentially unstable patient for data acquisition and analysis. Recently, a Doppler pulmonary artery catheter was introduced that measures beat-to-beat pulmonary artery blood flow-velocity, cross sectional area, and volume flow. Because of data indicating that acceleration of blood in the pulmonary artery (measured as the first derivative of either the velocity or flow waveform) is a sensitive indicator of right ventricular contractility, we have used waveforms obtained with the catheter for assessment of right ventricular pump function (stroke volume and peak pulmonary artery flow rate) and contractility in heart surgery patients. We report here our experience with this method in two patients undergoing left single lung transplantation.

Pulmonary artery location during microgravity activity: Potential impact for chest-mounted Doppler during space travel

NASA Technical Reports Server (NTRS)

Hadley, A. T., III; Conkin, J.; Waligora, J. M.; Horrigan, D. J., Jr.

1984-01-01

Doppler, or ultrasonic, monitoring for pain manifestations of decompression sickness (the bends) is accomplished by placing a sensor on the chest over the pulmonary artery and listening for bubbles. Difficulties have arisen because the technician notes that the pulmonary artery seems to move with subject movement in a one-g field and because the sensor output is influenced by only slight degrees of sensor movement. This study used two subjects and mapped the position of the pulmonary artery in one-g, microgravity, and two-g environments using ultrasound. The results showed that the pulmonary artery is fixed in location in microgravity and not affected by subject position change. The optimal position corresponded to where the Doppler signal is best heard with the subject in a supine position in a one-g environment. The impact of this result is that a proposed multiple sensor array on the chest proposed for microgravity use may not be necessary to monitor an astronaut during extravehicular activities. Instead, a single sensor of approximately 1 inch diameter and mounted in the position described above may suffice.

Beneficial effects of a novel agonist of the adenosine A2A receptor on monocrotaline-induced pulmonary hypertension in rats

PubMed Central

Alencar, Allan K N; Pereira, Sharlene L; Montagnoli, Tadeu L; Maia, Rodolfo C; Kümmerle, Arthur E; Landgraf, Sharon S; Caruso-Neves, Celso; Ferraz, Emanuelle B; Tesch, Roberta; Nascimento, José H M; de Sant'Anna, Carlos M R; Fraga, Carlos A M; Barreiro, Eliezer J; Sudo, Roberto T; Zapata-Sudo, Gisele

2013-01-01

Background and Purpose Pulmonary arterial hypertension (PAH) is characterized by enhanced pulmonary vascular resistance, right ventricular hypertrophy and increased right ventricular systolic pressure. Here, we investigated the effects of a N-acylhydrazone derivative, 3,4-dimethoxyphenyl-N-methyl-benzoylhydrazide (LASSBio-1359), on monocrotaline (MCT)-induced pulmonary hypertension in rats. Experimental Approach PAH was induced in male Wistar rats by a single i.p. injection of MCT (60 mg·kg−1) and 2 weeks later, oral LASSBio-1359 (50 mg·kg−1) or vehicle was given once daily for 14 days. Echocardiography was used to measure cardiac function and pulmonary artery dimensions, with histological assay of vascular collagen. Studies of binding to human recombinant adenosine receptors (A1, A2A, A3) and of docking with A2A receptors were also performed. Key Results MCT administration induced changes in vascular and ventricular structure and function, characteristic of PAH. These changes were reversed by treatment with LASSBio-1359. MCT also induced endothelial dysfunction in pulmonary artery, as measured by diminished relaxation of pre-contracted arterial rings, and this dysfunction was reversed by LASSBio-1359. In pulmonary artery rings from normal Wistar rats, LASSBio-1359 induced relaxation, which was decreased by the adenosine A2A receptor antagonist, ZM 241385. In adenosine receptor binding studies, LASSBio-1359 showed most affinity for the A2A receptor and in the docking analyses, binding modes of LASSBio-1359 and the A2A receptor agonist, CGS21680, were very similar. Conclusion and Implications In rats with MCT-induced PAH, structural and functional changes in heart and pulmonary artery were reversed by treatment with oral LASSBio-1359, most probably through the activation of adenosine A2A receptors. PMID:23530610

Impact of Pre-Stage II Hemodynamics and Pulmonary Artery Anatomy on 12-Month Outcome in the Single Ventricle Reconstruction Trial

PubMed Central

Aiyagari, Ranjit; Rhodes, John F.; Shrader, Peter; Radtke, Wolfgang A.; Bandisode, Varsha M.; Bergersen, Lisa; Gillespie, Matthew J.; Gray, Robert G.; Guey, Lin T.; Hill, Kevin D.; Hirsch, Russel; Kim, Dennis W.; Lee, Kyong-Jin; Pelech, Andrew N.; Ringewald, Jeremy; Takao, Cheryl; Vincent, Julie A.; Ohye, Richard G.

2014-01-01

Objective To compare interstage cardiac catheterization hemodynamic and angiographic findings between shunt types for Single Ventricle Reconstruction (SVR) trial. Background The SVR trial, which randomized subjects to modified Blalock-Taussig shunt (MBTS) or right ventricle-to-pulmonary artery shunt (RVPAS) for the Norwood procedure, demonstrated RVPAS was associated with smaller pulmonary artery diameter, but superior 12-month transplant-free survival. Methods We analyzed pre-stage II catheterization data for SVR trial subjects. Hemodynamic variables and shunt and pulmonary angiography were compared between shunt types; their association with 12-month transplant-free survival was also evaluated. Results Of 549 randomized subjects, 389 underwent pre-stage II catheterization. Smaller size, lower aortic and superior vena cava saturation, and higher ventricular end-diastolic pressure (EDP) were associated with worse 12-month transplant-free survival. MBTS subjects had lower coronary perfusion pressure (27mmHg vs. 32mmHg, P<0.001) and higher Qp:Qs ratio (1.1 vs. 1.0, P=0.009). Higher Qp:Qs ratio increased the risk of death or transplant only in the RVPAS group (P=0.01). MBTS subjects had fewer shunt (14% vs. 28%, P=0.004) and severe left pulmonary artery stenoses (0.7% vs. 9.2%, P=0.003), larger mid-main branch pulmonary artery diameters and higher Nakata index (164 vs. 134, P<0.001). Conclusions Compared with RVPAS subjects, MBTS subjects had more hemodynamic abnormalities related to shunt physiology, while RVPAS subjects had more shunt or pulmonary obstruction of a severe degree, and inferior pulmonary artery growth at pre-stage II catheterization. Lower BSA, higher ventricular EDP, and lower SVC saturation were associated with worse 12-month transplant-free survival. PMID:24332668

Bilateral multiple pulmonary artery aneurysms associated with cavitary pulmonary tuberculosis: a case report.

PubMed

Pallangyo, Pedro; Lyimo, Frederick; Bhalia, Smita; Makungu, Hilda; Nyangasa, Bashir; Lwakatare, Flora; Suranyi, Pal; Janabi, Mohamed

2017-07-19

Pulmonary artery aneurysms constitute <1% of aneurysms occurring in the thoracic cavity. Congenital cardiac defects are responsible for the majority (>50%) of cases, however, pulmonary artery aneurysm is a rare sequelae of pulmonary tuberculosis reported in about 5% of patients with chronic cavitary tuberculosis on autopsy. The natural history of this potentially fatal condition remains poorly understood and guidelines for optimal management are controversial. A 24-year-old man, a nursing student of African descent, was referred to us from an up-country regional hospital with a 4-week history of recurrent episodes of breathlessness, awareness of heartbeats and coughing blood 3 weeks after completing a 6-month course of anti-tuberculosis drugs. A physical examination revealed conjuctival and palmar pallor but there were no stigmata of connective tissue disorders, systemic vasculitides or congenital heart disease. An examination of the cardiovascular system revealed accentuated second heart sound (S 2 ) with early diastolic (grade 1/6) and holosystolic (grade 2/6) murmurs at the pulmonic and tricuspid areas respectively. Blood tests showed iron deficiency anemia, prolonged bleeding time, and mild hyponatremia. A chest radiograph revealed bilateral ovoid-shaped perihilar opacities while a computed tomography scan showed bilateral multiple pulmonary artery pseudoaneurysms with surrounding hematoma together with adjacent cystic changes, consolidations, and tree-in-bud appearance. Our patient refused to undergo surgery and died of aneurismal rupture after 9 days of hospitalization. The presence of intractable hemoptysis among patients with tuberculosis even after completion of anti-tuberculosis course should raise an index of suspicion for pulmonary artery aneurysm. Furthermore, despite of its rarity, early recognition and timely surgical intervention of pulmonary artery aneurysm is crucial to reducing morbidity and preventing the attributed mortality.

ASK1 Inhibition Halts Disease Progression in Preclinical Models of Pulmonary Arterial Hypertension.

PubMed

Budas, Grant R; Boehm, Mario; Kojonazarov, Baktybek; Viswanathan, Gayathri; Tian, Xia; Veeroju, Swathi; Novoyatleva, Tatyana; Grimminger, Friedrich; Hinojosa-Kirschenbaum, Ford; Ghofrani, Hossein A; Weissmann, Norbert; Seeger, Werner; Liles, John T; Schermuly, Ralph T

2018-02-01

Progression of pulmonary arterial hypertension (PAH) is associated with pathological remodeling of the pulmonary vasculature and the right ventricle (RV). Oxidative stress drives the remodeling process through activation of MAPKs (mitogen-activated protein kinases), which stimulate apoptosis, inflammation, and fibrosis. We investigated whether pharmacological inhibition of the redox-sensitive apical MAPK, ASK1 (apoptosis signal-regulating kinase 1), can halt the progression of pulmonary vascular and RV remodeling. A selective, orally available ASK1 inhibitor, GS-444217, was administered to two preclinical rat models of PAH (monocrotaline and Sugen/hypoxia), a murine model of RV pressure overload induced by pulmonary artery banding, and cellular models. Oral administration of GS-444217 dose dependently reduced pulmonary arterial pressure and reduced RV hypertrophy in PAH models. The therapeutic efficacy of GS-444217 was associated with reduced ASK1 phosphorylation, reduced muscularization of the pulmonary arteries, and reduced fibrotic gene expression in the RV. Importantly, efficacy was observed when GS-444217 was administered to animals with established disease and also directly reduced cardiac fibrosis and improved cardiac function in a model of isolated RV pressure overload. In cellular models, GS-444217 reduced phosphorylation of p38 and JNK (c-Jun N-terminal kinase) induced by adenoviral overexpression of ASK1 in rat cardiomyocytes and reduced activation/migration of primary mouse cardiac fibroblasts and human pulmonary adventitial fibroblasts derived from patients with PAH. ASK1 inhibition reduced pathological remodeling of the pulmonary vasculature and the right ventricle and halted progression of pulmonary hypertension in rodent models. These preclinical data inform the first description of a causal role of ASK1 in PAH disease pathogenesis.

Dysregulated renin-angiotensin-aldosterone system contributes to pulmonary arterial hypertension

PubMed Central

De Man, Frances; Tu, Ly; Handoko, Louis; Rain, Silvia; Ruiter, Gerrina; François, Charlène; Schalij, Ingrid; Dorfmüller, Peter; Simonneau, Gérald; Fadel, Elie; Perros, Frederic; Boonstra, Anco; Postmus, Piet; Van Der Velden, Jolanda; Vonk-Noordegraaf, Anton; Humbert, Marc; Eddahibi, Saadia; Guignabert, Christophe

2012-01-01

Rationale Patients with idiopathic pulmonary arterial hypertension (iPAH) often have a low cardiac output. To compensate, neurohormonal systems like renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system are upregulated but this may have long-term negative effects on the progression of iPAH. Objectives Assess systemic and pulmonary RAAS-activity in iPAH-patients and determine the efficacy of chronic RAAS-inhibition in experimental PAH. Measurements and Main Results We collected 79 blood samples from 58 iPAH-patients in the VU University Medical Center Amsterdam (between 2004–2010), to determine systemic RAAS-activity. We observed increased levels of renin, angiotensin (Ang) I and AngII, which was associated with disease progression (p<0.05) and mortality (p<0.05). To determine pulmonary RAAS-activity, lung specimens were obtained from iPAH-patients (during lung transplantation, n=13) and controls (during lobectomy or pneumonectomy for cancer, n=14). Local RAAS-activity in pulmonary arteries of iPAH-patients was increased, demonstrated by elevated ACE-activity in pulmonary endothelial cells and increased AngII type 1 (AT1) receptor expression and signaling. In addition, local RAAS- upregulation was associated with increased pulmonary artery smooth muscle cell proliferation via enhanced AT1-receptor signaling in iPAH-patients compared to controls. Finally, to determine the therapeutic potential of RAAS-activity, we assessed the chronic effects of an AT1-receptor antagonist (losartan) in the monocrotaline PAH-rat model (60 mg/kg). Losartan delayed disease progression, decreased RV afterload and pulmonary vascular remodeling and restored right ventricular-arterial coupling in PAH-rats. Conclusions Systemic and pulmonary RAAS-activities are increased in iPAH-patients and associated with increased pulmonary vascular remodeling. Chronic inhibition of RAAS by losartan is beneficial in experimental PAH. PMID:22859525

Hyperthyroidism enhances 5-HT-induced contraction of the rat pulmonary artery: role of calcium-activated chloride channel activation.

PubMed

Oriowo, Mabayoje A; Oommen, Elsie; Khan, Islam

2011-11-01

Experimentally-induced hyperthyroidism in rodents is associated with signs and symptoms of pulmonary hypertension. The main objective of the present study was to investigate the effect of thyroxine-induced pulmonary hypertension on the contractile response of the pulmonary artery to 5-HT and the possible underlying signaling pathway. 5-HT concentration-dependently contracted artery segments from control and thyroxine-treated rats with pD(2) values of 5.04 ± 0.19 and 5.34 ± 0.14, respectively. The maximum response was significantly greater in artery segments from thyroxine-treated rats. Neither BW 723C86 (5-HT(2B)-receptor agonist) nor CP 93129 (5-HT(1B)-receptor agonist) contracted ring segments of the pulmonary artery from control and thyroxine-treated rats at concentrations up to 10(-4)M. There was no significant difference in the level of expression of 5-HT(2A)-receptor protein between the two groups. Ketanserin (3 × 10(-8)M) produced a rightward shift of the concentration-response curve to 5-HT in both groups with equal potency (-logK(B) values were 8.1 ± 0.2 and 7.9 ± 0.1 in control and thyroxine-treated rats, respectively). Nifedipine (10(-6)M) inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. The calcium-activated chloride channel blocker, niflumic acid (10(-4)M) also inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. It was concluded that hyperthyroidism enhanced 5-HT-induced contractions of the rat pulmonary artery by a mechanism involving increased activity of calcium-activated chloride channels. Copyright © 2011 Elsevier B.V. All rights reserved.

Semi-quantitative assessment of pulmonary perfusion in children using dynamic contrast-enhanced MRI

NASA Astrophysics Data System (ADS)

Fetita, Catalin; Thong, William E.; Ou, Phalla

2013-03-01

This paper addresses the study of semi-quantitative assessment of pulmonary perfusion acquired from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in a study population mainly composed of children with pulmonary malformations. The automatic analysis approach proposed is based on the indicator-dilution theory introduced in 1954. First, a robust method is developed to segment the pulmonary artery and the lungs from anatomical MRI data, exploiting 2D and 3D mathematical morphology operators. Second, the time-dependent contrast signal of the lung regions is deconvolved by the arterial input function for the assessment of the local hemodynamic system parameters, ie. mean transit time, pulmonary blood volume and pulmonary blood flow. The discrete deconvolution method implements here a truncated singular value decomposition (tSVD) method. Parametric images for the entire lungs are generated as additional elements for diagnosis and quantitative follow-up. The preliminary results attest the feasibility of perfusion quantification in pulmonary DCE-MRI and open an interesting alternative to scintigraphy for this type of evaluation, to be considered at least as a preliminary decision in the diagnostic due to the large availability of the technique and to the non-invasive aspects.

Pulmonary hypertension in older adults.

PubMed

McArdle, John R; Trow, Terence K; Lerz, Kathryn

2007-12-01

Pulmonary hypertension is a frequently encountered problem in older patients. True idiopathic pulmonary arterial hypertension can also be seen and requires careful exclusion in older patients. Institution of therapies must be tempered with an appreciation of individual comorbidities and functional limitations that may affect patients' ability to comply and benefit from the complex treatments available for pulmonary arterial hypertension. This article reviews the existing data on the various forms of pulmonary hypertension presenting in older patients and on appropriate therapy in this challenging population.

Reliable and developmentally appropriate study end points are needed to achieve drug development for treatment of pediatric pulmonary arterial hypertension.

PubMed

Sun, H; Stockbridge, N; Ariagno, R L; Murphy, D; Nelson, R M; Rodriguez, W

2016-12-01

To identify suitable end points and surrogates for pediatric pulmonary arterial hypertension (PAH) as the lack of developmentally appropriate end point and clinical trials contribute to the unmet medical need. Reviewed the efficacy end points and surrogates for all trials (1995 to 2013) that were submitted to the Food and Drug Administration (FDA) to support the approval of PAH therapy and conducted literature search. An increase in the 6 min walking distance (6MWD) was used as a primary end point in 8/9 adult PAH trials. This end point is not suitable for infants and young children because of performance limitations and lack of control data. One adult PAH trial used time to the first morbidity or mortality event as a primary end point, which could potentially be used in pediatric PAH trials. In the sildenafil pediatric PAH trial, the change in pulmonary vascular resistance index or mean pulmonary artery pressure was used as a surrogate for the 6MWD to assess exercise capacity. However, two deaths and three severe adverse events during the catheterizations made this an unacceptably high-risk surrogate. The INOmax persistent pulmonary hypertension of the newborn trial used a reduction in initiation of extracorporeal membrane oxygenation treatment as a primary end point, which is not feasible for other pediatric PAH trials. A Literature review revealed none of the existing noninvasive markers are fully validated as surrogates to assess PAH efficacy and long-term safety. For pediatric PAH trials, clinical end points are acceptable, and novel validated surrogates would be helpful. FDA seeks collaboration with academia, industry and parents to develop other suitable and possibly more efficient efficacy end points to facilitate pediatric PAH drug development.

High-resolution computed tomography evaluation of the bronchial lumen to vertebral body diameter and pulmonary artery to vertebral body diameter ratios in anesthetized ventilated normal cats.

PubMed

Lee-Fowler, Tekla M; Cole, Robert C; Dillon, A Ray; Tillson, D Michael; Garbarino, Rachel; Barney, Sharron

2017-10-01

Objectives Bronchial lumen to pulmonary artery diameter (BA) ratio has been utilized to investigate pulmonary pathology on high-resolution CT images. Diseases affecting both the bronchi and pulmonary arteries render the BA ratio less useful. The purpose of the study was to establish bronchial lumen diameter to vertebral body diameter (BV) and pulmonary artery diameter to vertebral body diameter (AV) ratios in normal cats. Methods Using high-resolution CT images, 16 sets of measurements (sixth thoracic vertebral body [mid-body], each lobar bronchi and companion pulmonary artery diameter) were acquired from young adult female cats and 41 sets from pubertal female cats. Results Young adult and pubertal cat BV ratios were not statistically different from each other in any lung lobe. Significant differences between individual lung lobe BV ratios were noted on combined age group analysis. Caudal lung lobe AV ratios were significantly different between young adult and pubertal cats. All other lung lobe AV ratios were not significantly different. Caudal lung lobe AV ratios were significantly different from all other lung lobes but not from each other in both the young adult and pubertal cats. Conclusions and relevance BV ratio reference intervals determined for individual lung lobes could be applied to both young adult and pubertal cats. Separate AV ratios for individual lung lobes would be required for young adult and pubertal cats. These ratios should allow more accurate evaluation of cats with concurrent bronchial and pulmonary arterial disease.

Factors affecting the response to exercise in patients with severe pulmonary arterial hypertension.

PubMed

Flox-Camacho, Angela; Escribano-Subías, Pilar; Jiménez-López Guarch, Carmen; Fernández-Vaquero, Almudena; Martín-Ríos, Dolores; de la Calzada-Campo, Carlos Sáenz

2011-01-01

Ergospirometry objectively quantifies exercise capacity. Up until now, the response to exercise evaluated by ergospirometry in patients with pulmonary arterial hypertension has only been described in recently diagnosed.patients. Our aim is to describe the response to exercise in patients with severe pulmonary arterial hypertension under specific treatment and define which parameters determine their exercise capacity. A cross-sectional study was performed on 80 patients, 57 women, aged 45 (14), with severe pulmonary arterial hypertension (48 idiopathic, 14 related to toxic rapeseed oil, 13 to connective tissue disease, 5 to human immunodeficiency virus), mean pulmonary pressure at diagnosis 61(15)mmHg and after 49(33) months under treatment since diagnosis. Biomarkers were measured and echocardiography and ergospirometry were performed the same day. Our patients, under specific treatment, showed the typical behaviour of patients with pulmonary arterial hypertension with less limitation of both aerobic capacity and ventilatory efficiency. Being male (p=0.004), high ventilatory equivalent for carbon dioxide at anaerobic threshold (p<0.001) or biomarkers (p=0.006) were the strongest predictors of impaired peak oxygen uptake in multivariate analysis, whereas for an impaired percentage achieved of predicted value were right ventricle diastolic diameter (p<0.001), months of treatment (p=0.01) and high ventilatory equivalent for CO(2) (p<0.001). In pulmonary arterial hypertension, right ventricle dysfunction (expressed by its dilation or high NTproBNP) and impaired ventilatory inefficiency as well as being male or a short time under treatment can be considered as determining factors of impaired exercise capacity. Copyright © 2010 SEPAR. Published by Elsevier Espana. All rights reserved.

Relationship between interatrial communication, ductus arteriosus, and pulmonary flow patterns in fetuses with transposition of the great arteries: prediction of neonatal desaturation.

PubMed

Vaujois, Laurence; Boucoiran, Isabelle; Preuss, Christophe; Brassard, Myriam; Houde, Christine; Fouron, Jean C; Raboisson, Marie-Josée

2017-09-01

The relationship between interatrial communication, ductus arteriosus, and pulmonary flow in transposition of the great arteries and intact ventricular septum may help predict postnatal desaturation. Echocardiographic data of 45 fetuses with transposition of the great arteries and intact ventricular septum and 50 age-matched controls were retrospectively reviewed. Interatrial communication, left and right ventricular output, flow in the ductus arteriosus, as well as effective pulmonary flow were measured. Patients were divided into two groups on the basis of postnatal saturations: group 1 had saturations ⩽50% and group 2 >50%. Of 45 fetuses, 13 (26.7%) were classified into group 1. Compared with fetuses in group 2, they had a smaller interatrial communication (2.9 versus 4.0 mm, p=0.004) and more retrograde diastolic flow in the ductus arteriosus (92 versus 23%, p=0.002). Both groups showed a significant decrease in ductal flow compared with controls. Patients in group 2 had a higher effective pulmonary flow compared with controls. There was a mild correlation between left ventricular output and size of the interatrial communication (Spearman's rank correlation 0.44). A retrograde diastolic flow is present in most of the fetuses with postnatal desaturation. Fetuses with transposition of the great arteries have a lower flow through the ductus arteriosus compared with controls. Fetuses without restrictive foramen ovale have higher effective pulmonary flow. Peripheral pulmonary vasodilatation due to higher oxygen saturation in pulmonary arteries in the case of transposition of the great arteries could be one possible cause.

Development of anatomophysiologic knowledge regarding the cardiovascular system: from Egyptians to Harvey.

PubMed

Bestetti, Reinaldo Bulgarelli; Restini, Carolina Baraldi A; Couto, Lucélio B

2014-12-01

Our knowledge regarding the anatomophysiology of the cardiovascular system (CVS) has progressed since the fourth millennium BC. In Egypt (3500 BC), it was believed that a set of channels are interconnected to the heart, transporting air, urine, air, blood, and the soul. One thousand years later, the heart was established as the center of the CVS by the Hippocratic Corpus in the medical school of Kos, and some of the CVS anatomical characteristics were defined. The CVS was known to transport blood via the right ventricle through veins and the pneuma via the left ventricle through arteries. Two hundred years later, in Alexandria, following the development of human anatomical dissection, Herophilus discovered that arteries were 6 times thicker than veins, and Erasistratus described the semilunar valves, emphasizing that arteries were filled with blood when ventricles were empty. Further, 200 years later, Galen demonstrated that arteries contained blood and not air. With the decline of the Roman Empire, Greco-Roman medical knowledge about the CVS was preserved in Persia, and later in Islam where, Ibn Nafis inaccurately described pulmonary circulation. The resurgence of dissection of the human body in Europe in the 14th century was associated with the revival of the knowledge pertaining to the CVS. The main findings were the description of pulmonary circulation by Servetus, the anatomical discoveries of Vesalius, the demonstration of pulmonary circulation by Colombo, and the discovery of valves in veins by Fabricius. Following these developments, Harvey described blood circulation.

Development of Anatomophysiologic Knowledge Regarding the Cardiovascular System: From Egyptians to Harvey.

PubMed

Bestetti, Reinaldo Bulgarelli; Restini, Carolina Baraldi A; Couto, Lucélio B

2014-10-10

Our knowledge regarding the anatomophysiology of the cardiovascular system (CVS) has progressed since the fourth millennium BC. In Egypt (3500 BC), it was believed that a set of channels are interconnected to the heart, transporting air, urine, air, blood, and the soul. One thousand years later, the heart was established as the center of the CVS by the Hippocratic Corpus in the medical school of Kos, and some of the CVS anatomical characteristics were defined. The CVS was known to transport blood via the right ventricle through veins and the pneuma via the left ventricle through arteries. Two hundred years later, in Alexandria, following the development of human anatomical dissection, Herophilus discovered that arteries were 6 times thicker than veins, and Erasistratus described the semilunar valves, emphasizing that arteries were filled with blood when ventricles were empty. Further, 200 years later, Galen demonstrated that arteries contained blood and not air. With the decline of the Roman Empire, Greco-Roman medical knowledge about the CVS was preserved in Persia, and later in Islam where, Ibn Nafis inaccurately described pulmonary circulation. The resurgence of dissection of the human body in Europe in the 14th century was associated with the revival of the knowledge pertaining to the CVS. The main findings were the description of pulmonary circulation by Servetus, the anatomical discoveries of Vesalius, the demonstration of pulmonary circulation by Colombo, and the discovery of valves in veins by Fabricius. Following these developments, Harvey described blood circulation.

Development of Anatomophysiologic Knowledge Regarding the Cardiovascular System: From Egyptians to Harvey

PubMed Central

Bestetti, Reinaldo Bulgarelli; Restini, Carolina Baraldi A.; Couto, Lucélio B.

2014-01-01

Our knowledge regarding the anatomophysiology of the cardiovascular system (CVS) has progressed since the fourth millennium BC. In Egypt (3500 BC), it was believed that a set of channels are interconnected to the heart, transporting air, urine, air, blood, and the soul. One thousand years later, the heart was established as the center of the CVS by the Hippocratic Corpus in the medical school of Kos, and some of the CVS anatomical characteristics were defined. The CVS was known to transport blood via the right ventricle through veins and the pneuma via the left ventricle through arteries. Two hundred years later, in Alexandria, following the development of human anatomical dissection, Herophilus discovered that arteries were 6 times thicker than veins, and Erasistratus described the semilunar valves, emphasizing that arteries were filled with blood when ventricles were empty. Further, 200 years later, Galen demonstrated that arteries contained blood and not air. With the decline of the Roman Empire, Greco-Roman medical knowledge about the CVS was preserved in Persia, and later in Islam where, Ibn Nafis inaccurately described pulmonary circulation. The resurgence of dissection of the human body in Europe in the 14th century was associated with the revival of the knowledge pertaining to the CVS. The main findings were the description of pulmonary circulation by Servetus, the anatomical discoveries of Vesalius, the demonstration of pulmonary circulation by Colombo, and the discovery of valves in veins by Fabricius. Following these developments, Harvey described blood circulation. PMID:25590934

Complete remission of a case of hepatocellular carcinoma with tumor invasion in inferior vena cava and with pulmonary metastasis successfully treated with repeated arterial infusion chemotherapy.

PubMed

Kogure, Takayuki; Iwasaki, Takao; Ueno, Yoshiyuki; Kanno, Noriatsu; Fukushima, Koji; Yamagiwa, Yoko; Nagasaki, Futoshi; Kakazu, Eiji; Matsuda, Yasunori; Kido, Osamu; Nakagome, Yu; Ninomiya, Masashi; Shimosegawa, Tooru

2007-01-01

We report the case of a patient having hepatocellular carcinoma with tumor invasion to the inferior vena cava and with multiple pulmonary metastases who was treated with repeated one-shot administration of epirubicin, cisplatin, and mitomycin C by hepatic artery and bronchial artery, which led to complete remission. A 72-year-old woman was diagnosed with infiltrative hepatocellular carcinoma with Vv3, multiple intrahepatic metastases, and multiple pulmonary metastases associated with compensated liver cirrhosis. One-shot infusion of epirubicin, cisplatin, and mitomycin C was performed through proper hepatic artery and bronchial artery for twice at eight weeks of intervals. Pulmonary metastases disappeared and intrahepatic lesions indicated marked shrinkage leaving a scar-like lesion with decreases in tumor markers. After six months and 20 months, tumor markers indicated increasing tendency but no evident recurrence was found by computed tomography or hepatic arteriography. One-shot infusion of the same regimens through proper hepatic artery was performed and tumor markers decreased to normal levels. After 14 months of the last therapy, no evidence of recurrence has been found on image analysis or in tumor markers. This arterial infusion therapy is well tolerated for the patients with compensated liver cirrhosis and might be promising for the effective treatment of advanced hepatocellular carcinoma with pulmonary metastases.

Pulmonary vascular input impedance is a combined measure of pulmonary vascular resistance and stiffness and predicts clinical outcomes better than pulmonary vascular resistance alone in pediatric patients with pulmonary hypertension.

PubMed

Hunter, Kendall S; Lee, Po-Feng; Lanning, Craig J; Ivy, D Dunbar; Kirby, K Scott; Claussen, Lori R; Chan, K Chen; Shandas, Robin

2008-01-01

Pulmonary vascular resistance (PVR) is the current standard for evaluating reactivity in children with pulmonary arterial hypertension (PAH). However, PVR measures only the mean component of right ventricular afterload and neglects pulsatile effects. We recently developed and validated a method to measure pulmonary vascular input impedance, which revealed excellent correlation between the zero harmonic impedance value and PVR and suggested a correlation between higher-harmonic impedance values and pulmonary vascular stiffness. Here we show that input impedance can be measured routinely and easily in the catheterization laboratory, that impedance provides PVR and pulmonary vascular stiffness from a single measurement, and that impedance is a better predictor of disease outcomes compared with PVR. Pressure and velocity waveforms within the main pulmonary artery were measured during right heart catheterization of patients with normal pulmonary artery hemodynamics (n = 14) and those with PAH undergoing reactivity evaluation (49 subjects, 95 conditions). A correction factor needed to transform velocity into flow was obtained by calibrating against cardiac output. Input impedance was obtained off-line by dividing Fourier-transformed pressure and flow waveforms. Exceptional correlation was found between the indexed zero harmonic of impedance and indexed PVR (y = 1.095x + 1.381, R2 = 0.9620). In addition, the modulus sum of the first 2 harmonics of impedance was found to best correlate with indexed pulse pressure over stroke volume (y = 13.39x - 0.8058, R2 = 0.7962). Among a subset of patients with PAH (n = 25), cumulative logistic regression between outcomes to total indexed impedance was better (R(L)2 = 0.4012) than between outcomes and indexed PVR (R(L)2 = 0.3131). Input impedance can be consistently and easily obtained from pulse-wave Doppler and a single catheter pressure measurement, provides comprehensive characterization of the main components of RV afterload, and better predicts patient outcomes compared with PVR alone.

Effect of chronic perinatal hypoxia on the role of rho-kinase in pulmonary artery contraction in newborn lambs

PubMed Central

Terry, Michael H.; Merritt, Travis A.; Papamatheakis, Demosthenes G.; Blood, Quintin; Ross, Jonathon M.; Power, Gordon G.; Longo, Lawrence D.; Wilson, Sean M.

2013-01-01

Exposure to chronic hypoxia during gestation predisposes infants to neonatal pulmonary hypertension, but the underlying mechanisms remain unclear. Here, we test the hypothesis that moderate continuous hypoxia during gestation causes changes in the rho-kinase pathway that persist in the newborn period, altering vessel tone and responsiveness. Lambs kept at 3,801 m above sea level during gestation and the first 2 wk of life were compared with those with gestation at low altitude. In vitro studies of isolated pulmonary arterial rings found a more forceful contraction in response to KCl and 5-HT in high-altitude compared with low-altitude lambs. There was no difference between the effects of blockers of various pathways of extracellular Ca2+ entry in low- and high-altitude arteries. In contrast, inhibition of rho-kinase resulted in significantly greater attenuation of 5-HT constriction in high-altitude compared with low-altitude arteries. High-altitude lambs had higher baseline pulmonary artery pressures and greater elevations in pulmonary artery pressure during 15 min of acute hypoxia compared with low-altitude lambs. Despite evidence for an increased role for rho-kinase in high-altitude arteries, in vivo studies found no significant difference between the effects of rho-kinase inhibition on hypoxic pulmonary vasoconstriction in intact high-altitude and low-altitude lambs. We conclude that chronic hypoxia in utero results in increased vasopressor response to both acute hypoxia and serotonin, but that rho-kinase is involved only in the increased response to serotonin. PMID:23152110

Pulmonary changes in liver transplant candidates with hepatitis C cirrhosis.

PubMed

Al-Moamary, M S; Gorka, T; Al-Traif, I H; Al-Jahdali, H H; Al-Shimemeri, A A; Al-Kanway, B; Abdulkareeem, A A; Abdulkareeem, A A

2001-12-01

Several studies have shown that pulmonary abnormalities are common in patients with end-stage liver disease. However, most of these studies were conducted on patients with heterogeneous etiologies. Therefore, we studied these changes in a homogenous group of hepatitis C cirrhotic patients who were potential candidates for liver transplantation. The charts of 81 patients from King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia with hepatitis C cirrhosis who were evaluated for liver transplantation were reviewed. The following data was retrieved: echocardiography with micro-bubble study, arterial blood gases, and pulmonary function tests of 81 candidates and reviewed over 3 years from 1994 to 1997. The mean age was 53 (+/-9) years with male to female ratio of 1.4:1. Echocardiographic micro-bubble study, revealed 4 of 62 (7%) had an intrapulmonary shunt. Arterial blood gases results were pH of 7.44 (+/-0.4), partial arterial tension of carbon dioxide of 33 mm Hg (+/-4), partial arterial tension of oxygen of 84 mm Hg (+/-12), and alveolar-arterial gradient of 30 mm Hg (+/-10). Eleven percent had obstructive airway disease, 17% had restrictive lung impairment, and 43% had reduced diffusion capacity. Seventy five percent of patients with reduced diffusion capacity had normal lung volumes. Various pulmonary function test abnormalities did not lead to significant differences in arterial blood gases. Pulmonary changes were frequent in liver transplant candidates with hepatitis C virus cirrhosis with reduced diffusion capacity being the most. Apart from the effect of hepatopulmonary syndrome on arterial oxygenation, other pulmonary abnormalities were not significantly different.

Pulmonary artery sarcoma with angiosarcoma phenotype mimicking pleomorphic malignant fibrous histiocytoma: a case report

PubMed Central

2012-01-01

Abstract Primary sarcomas of the major blood vessels can be classified based on location in relationship to the wall or by histologic type. Angiosarcomas are malignant neoplasms that arise from the endothelial lining of the blood vessels; those arising in the intimal compartment of pulmonary artery are rare. We report a case of pulmonary artery angiosarcoma in a 36-year old female with pulmonary masses. The patient had no other primary malignant neoplasm, thus excluding a metastatic lesion. Gross examination revealed a thickened right pulmonary artery and a necrotic and hemorrhagic tumor, filling and occluding the vascular lumen. The mass extended distally, within the pulmonary vasculature of the right lung. Microscopically, an intravascular undifferentiated tumor was identified. The tumor cells showed expression for vascular markers VEGFR, VEGFR3, PDGFRa, FGF, Ulex europaeus, FVIII, FLI-1, CD31 and CD34; p53 was overexpressed and Ki67 proliferative rate was increased. Intravascular angiosarcomas are aggressive neoplasms, often associated with poor outcome. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2315906377648045. PMID:23134683

Patent ductus arteriosus in an adult cat with pulmonary hypertension and right-sided congestive heart failure: hemodynamic evaluation and clinical outcome following ductal closure.

PubMed

Novo-Matos, José; Hurter, Karin; Bektas, Rima; Grest, Paula; Glaus, Tony

2014-09-01

Right-sided congestive heart failure (CHF) developed secondary to severe pulmonary hypertension (PH) in an 8-year-old cat with a left-to-right shunting patent ductus arteriosus (PDA). Vascular reactivity was tested prior to shunt ligation by treatment with oxygen and sildenafil. This treatment was associated with a significant decrease in pulmonary artery pressure as assessed by echocardiography. Subsequently surgical shunt ligation was planned. During thoracotomy, digital occlusion of the PDA was performed for 10 min with simultaneous catheter measurement of right ventricular pressure, which did not increase. Permanent shunt ligation resulted in a complete and sustained clinical recovery. A lung biopsy sample obtained during thoracotomy demonstrated histopathological arterial changes typical of PH. Cats can develop clinically severe PH and right-sided CHF secondary to a left-to-right PDA even at an advanced age. Assuming there is evidence of pulmonary reactivity, PDA occlusion might be tolerated and can potentially produce long-term clinical benefits. Copyright © 2014 Elsevier B.V. All rights reserved.

2014 Guidelines of Taiwan Society of Cardiology (TSOC) for the Management of Pulmonary Arterial Hypertension

PubMed Central

Hsu, Chih-Hsin; Ho, Wan-Jing; Huang, Wei-Chun; Chiu, Yu-Wei; Hsu, Tsu-Shiu; Kuo, Ping-Hung; Hsu, Hsao-Hsun; Chang, Jia-Kan; Cheng, Chin-Chang; Lai, Chao-Lun; Liang, Kae-Woei; Lin, Shoa-Lin; Sung, Hsao-Hsun; Tsai, Wei-Chuan; Weng, Ken-Pen; Hsieh, Kai-Sheng; Yin, Wei-Hsian; Lin, Shing-Jong; Wang, Kuo-Yang

2014-01-01

Pulmonary hypertension (PH) is a hemodynamic and pathophysiologic condition, defined as a mean pulmonary arterial pressure exceeding 25 mmHg at rest. According to the recent classifications, it is grouped into pulmonary arterial hypertension (PAH), heart-related, lung-related, thromboembolic, and miscellaneous PH. In the past two decades, tremendous advances have occurred in the field of PH. These include (1) development of clinical diagnostic algorithm and a monitoring strategy dedicated to PAH, (2) defining strong rationales for screening at-risk populations, (3) advent of pulmonary specific drugs which makes PAH manageable, (4) recognition of needs of having proper strategy of combining existing pulmonary specific drugs, and/or potential novel drugs, (5) pursuit of clinical trials with optimal surrogate endpoints and study durations, (6) recognition of critical roles of PH/right ventricular function, as well as interdependence of ventricles in different conditions, especially those with various phenotypes of heart failure, and (7) for rare diseases, putting equal importance on carefully designed observation studies, various registries, etc., besides double blind randomized studies. In addition, ongoing basic and clinical research has led to further understanding of relevant physiology, pathophysiology, epidemiology and genetics of PH/PAH. This guidelines from the working group of Pulmonary Hypertension of the Taiwan Society of Cardiology is to provide updated guidelines based on the most recent international guidelines as well as Taiwan’s domestic research on PH. The guidelines are mainly for the management of PAH (Group 1) ; however the majority of content can be helpful for managing other types of PH. PMID:27122817

Moyamoya disease and artery tortuosity as rare phenotypes in a patient with an elastin mutation.

PubMed

Ishiwata, Tsukasa; Tanabe, Nobuhiro; Shigeta, Ayako; Yokota, Hajime; Tsushima, Kenji; Terada, Jiro; Sakao, Seiichiro; Morisaki, Hiroko; Morisaki, Takayuki; Tatsumi, Koichiro

2016-07-01

Sporadic and familial elastin mutations can occur in large vessel stenosis such as supravalvular aortic stenosis and narrowing of the descending aorta. However, there are very few reports regarding the arteriopathy of cerebral, pulmonary or abdominal arteries in elastin mutations. We herein report the case of a Japanese female patient presenting with multiple arteriopathy including moyamoya disease, a tortuosity of abdominal arteries and pulmonary hypertension due to peripheral pulmonary artery stenosis. This case suggests the possible progression of cerebral arteriopathy including moyamoya disease in patients with elastin mutations. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Varied response of the pulmonary arterial endothelium in a novel rat model of venous thromboembolism.

PubMed

Ji, Ying-qun; Feng, Min; Zhang, Zhong-he; Lu, Wei-xuan; Wang, Chen

2013-01-01

The experimental studies of venous thromboembolism (VTE) as an entity and the response of the pulmonary arterial endothelium after VTE are still rare. The objective of this study was to observe changes in the pulmonary arterial endothelium using a novel rat model of VTE. Rats were allocated to the VTE (n = 54) or control groups (n = 9). The left femoral vein was blocked using a microvessel clip to form deep vein thrombosis (DVT). One, four or seven-day-old thrombi were injected into the right femoral vein to induce DVT-pulmonary thromboembolism (DVT-PTE). The rats were sacrificed 1, 4 or 7 days later (D(n(1,4,7)) P(n(1,4,7)) subgroups (n = 6)), and the lungs were examined using light and electron microscopy. On gross dissection, the rate of DVT formation was higher on day 1 (D(1)P(n): 100%, 18/18) than day 4 (D(4)P(n): 83%, 15/18; χ(2) = 5.900, P = 0.015) or day 7 (D(7)P(n): 44%, 8/18; χ(2) = 13.846, P = 0.000). On gross dissection, the positive emboli residue rate in the pulmonary arteries was lower in the D(1)P(n) subgroup (39%, 7/18) than the D(4)P(n) (73%, 11/15; χ(2) = 3.915, P = 0.048) and D(7)P(n) subgroups (100%, 8/8; χ(2) = 8.474, P = 0.004); however, light microscopy indicated the residual emboli rate was similar in all subgroups. Hyperplasia of the pulmonary arterial endothelium was observed 4 and 7 days after the injection of one-day-old or four-day-old thrombi. However, regions without pulmonary arterial endothelial cells and intra-elastic layers were observed one day after injection of seven-day-old thrombi. This novel model closely simulates the clinical situations of thrombus formation and is ideal to study pulmonary endothelial cell activation. The outcome of emboli and pulmonary arterial endothelial alterations are related to the age and nature of the thrombi.

Patent ductus arteriosus: patho-physiology, hemodynamic effects and clinical complications.

PubMed

Capozzi, Giovanbattista; Santoro, Giuseppe

2011-10-01

During fetal life, patent arterial duct diverts placental oxygenated blood from the pulmonary artery into the aorta by-passing lungs. After birth, decrease of prostacyclins and prostaglandins concentration usually causes arterial duct closure. This process may be delayed, or may even completely fail in preterm infants with arterial duct still remaining patent. If that happens, blood flow by-pass of the systemic circulation through the arterial duct results in pulmonary overflow and systemic hypoperfusion. When pulmonary flow is 50% higher than systemic flow, a hemodynamic "paradox" results, with an increase of left ventricular output without a subsequent increase of systemic output. Cardiac overload support neuro-humoral effects (activation of sympathetic nervous system and renin-angiotensin system) that finally promote heart failure. Moreover, increased pulmonary blood flow can cause vascular congestion and pulmonary edema. However, the most dangerous effect is cerebral under-perfusion due to diastolic reverse-flow and resulting in cerebral hypoxia. At last, blood flow decreases through the abdominal aorta, reducing perfusion of liver, gut and kidneys and may cause hepatic failure, renal insufficiency and necrotizing enterocolitis. Conclusions Large patent arterial duct may cause life-threatening multi-organ effects. In pre-term infant early diagnosis and timely effective treatment are cornerstones in the prevention of cerebral damage and long-term multi-organ failure.

Riociguat

MedlinePlus

... is used to treat pulmonary arterial hypertension (PAH; high blood pressure in the vessels that carry blood to the ... used to treat chronic thromboembolic pulmonary hypertension (CTEPH; high blood pressure in the lung arteries caused by blood clots ...

Noninvasive Doppler Tissue Measurement of Pulmonary Artery Compliance in Children with Pulmonary Hypertension

PubMed Central

Dyer, Karrie; Lanning, Craig; Das, Bibhuti; Lee, Po-Feng; Ivy, D. Dunbar; Valdes-Cruz, Lilliam; Shandas, Robin

2007-01-01

Background We have shown previously that input impedance of the pulmonary vasculature provides a comprehensive characterization of right ventricular afterload by including compliance. However, impedance-based compliance assessment requires invasive measurements. Here, we develop and validate a noninvasive method to measure pulmonary artery (PA) compliance using ultrasound color M-mode (CMM) Doppler tissue imaging (DTI). Methods Dynamic compliance (Cdyn) of the PA was obtained from CMM DTI and continuous wave Doppler measurement of the tricuspid regurgitant velocity. Cdyn was calculated as: [(Ds − Dd)/(Dd × Ps)] × 104; where Ds = systolic diameter, Dd = diastolic diameter, and Ps = systolic pressure. The method was validated both in vitro and in 13 patients in the catheterization laboratory, and then tested on 27 pediatric patients with pulmonary hypertension, with comparison with 10 age-matched control subjects. Cdyn was also measured in an additional 13 patients undergoing reactivity studies. Results Instantaneous diameter measured using CMM DTI agreed well with intravascular ultrasound measurements in the in vitro models. Clinically, Cdyn calculated by CMM DTI agreed with Cdyn calculated using invasive techniques (23.4 ± 16.8 vs 29.1 ± 20.6%/100 mm Hg; P = not significant). Patients with pulmonary hypertension had significantly lower peak wall velocity values and lower Cdyn values than control subjects (P < .01). Cdyn values followed an exponentially decaying relationship with PA pressure, indicating the nonlinear stress–strain behavior of these arteries. Reactivity in Cdyn agreed with reactivity measured using impedance techniques. Conclusion The Cdyn method provides a noninvasive means of assessing PA compliance and should be useful as an additional measure of vascular reactivity subsequent to pulmonary vascular resistance in patients with pulmonary hypertension. PMID:16581479

Noninvasive Doppler tissue measurement of pulmonary artery compliance in children with pulmonary hypertension.

PubMed

Dyer, Karrie; Lanning, Craig; Das, Bibhuti; Lee, Po-Feng; Ivy, D Dunbar; Valdes-Cruz, Lilliam; Shandas, Robin

2006-04-01

We have shown previously that input impedance of the pulmonary vasculature provides a comprehensive characterization of right ventricular afterload by including compliance. However, impedance-based compliance assessment requires invasive measurements. Here, we develop and validate a noninvasive method to measure pulmonary artery (PA) compliance using ultrasound color M-mode (CMM) Doppler tissue imaging (DTI). Dynamic compliance (C(dyn)) of the PA was obtained from CMM DTI and continuous wave Doppler measurement of the tricuspid regurgitant velocity. C(dyn) was calculated as: [(D(s) - D(d))/(D(d) x P(s))] x 10(4); where D(s) = systolic diameter, D(d) = diastolic diameter, and P(s) = systolic pressure. The method was validated both in vitro and in 13 patients in the catheterization laboratory, and then tested on 27 pediatric patients with pulmonary hypertension, with comparison with 10 age-matched control subjects. C(dyn) was also measured in an additional 13 patients undergoing reactivity studies. Instantaneous diameter measured using CMM DTI agreed well with intravascular ultrasound measurements in the in vitro models. Clinically, C(dyn) calculated by CMM DTI agreed with C(dyn) calculated using invasive techniques (23.4 +/- 16.8 vs 29.1 +/- 20.6%/100 mm Hg; P = not significant). Patients with pulmonary hypertension had significantly lower peak wall velocity values and lower C(dyn) values than control subjects (P < .01). C(dyn) values followed an exponentially decaying relationship with PA pressure, indicating the nonlinear stress-strain behavior of these arteries. Reactivity in C(dyn) agreed with reactivity measured using impedance techniques. The C(dyn) method provides a noninvasive means of assessing PA compliance and should be useful as an additional measure of vascular reactivity subsequent to pulmonary vascular resistance in patients with pulmonary hypertension.

High-altitude pulmonary hypertension is associated with a free radical-mediated reduction in pulmonary nitric oxide bioavailability

PubMed Central

Bailey, Damian M; Dehnert, Christoph; Luks, Andrew M; Menold, Elmar; Castell, Christian; Schendler, Guido; Faoro, Vitalie; Gutowski, Mariusz; Evans, Kevin A; Taudorf, Sarah; James, Philip E; McEneny, J; Young, Ian S; Swenson, Erik R; Mairbäurl, Heimo; Bärtsch, Peter; Berger, Marc M

2010-01-01

High altitude (HA)-induced pulmonary hypertension may be due to a free radical-mediated reduction in pulmonary nitric oxide (NO) bioavailability. We hypothesised that the increase in pulmonary artery systolic pressure (PASP) at HA would be associated with a net transpulmonary output of free radicals and corresponding loss of bioactive NO metabolites. Twenty-six mountaineers provided central venous and radial arterial samples at low altitude (LA) and following active ascent to 4559 m (HA). PASP was determined by Doppler echocardiography, pulmonary blood flow by inert gas re-breathing, and vasoactive exchange via the Fick principle. Acute mountain sickness (AMS) and high-altitude pulmonary oedema (HAPE) were diagnosed using clinical questionnaires and chest radiography. Electron paramagnetic resonance spectroscopy, ozone-based chemiluminescence and ELISA were employed for plasma detection of the ascorbate free radical (A·−), NO metabolites and 3-nitrotyrosine (3-NT). Fourteen subjects were diagnosed with AMS and three of four HAPE-susceptible subjects developed HAPE. Ascent decreased the arterio-central venous concentration difference (a-cvD) resulting in a net transpulmonary loss of ascorbate, α-tocopherol and bioactive NO metabolites (P < 0.05 vs. LA). This was accompanied by an increased a-cvD and net output of A·− and lipid hydroperoxides (P < 0.05 vs. sea level, SL) that correlated against the rise in PASP (r= 0.56–0.62, P < 0.05) and arterial 3-NT (r= 0.48–0.63, P < 0.05) that was more pronounced in HAPE. These findings suggest that increased PASP and vascular resistance observed at HA are associated with a free radical-mediated reduction in pulmonary NO bioavailability. PMID:20876202

Anomalous origin of circumflex coronary artery from right pulmonary artery in a hypoplastic left heart syndrome child

PubMed Central

Kansy, Andrzej; Łaniewski-Wołłk, Przemysław

2014-01-01

We describe the case of a newborn with hypoplastic left heart syndrome (HLHS) and aberrant origin of the circumflex coronary artery from the right pulmonary artery. The patient underwent a modified Norwood procedure with direct reimplantation of the circumflex coronary artery to the neo-aorta, but died on the 5th postoperative day because of myocardial failure. Detailed assessment of coronary arteries as part of the routine echocardiographic evaluation of HLHS and intraoperative inspection of them is crucial. PMID:26336423

Pathogenesis of solitary right aortic arch: a mass effect hypothesis based on observations of serial human embryonic sections.

PubMed

Jin, Zhe W; Yamada, Tomonori; Kim, Ji H; Rodríguez-Vázquez, José F; Murakami, Gen; Arakawa, Keiji

2017-03-01

In general, solitary right aortic arch carries the left-sided ductus arteriosus communicating between the left subclavian and pulmonary arteries or the right-sided ductus connecting the descending aorta to the left pulmonary artery. Serial sections of fifteen 5- to 6-week-old embryos and ten 8- to 9-week-old fetuses suggested that the pathogenesis was unrelated to inversion due to dysfunction in gene cascades that control the systemic left/right axis. With inversion, conversely, the ductus or the sixth pharyngeal arch artery should connect to the right pulmonary artery. The disappearance of the right aortic arch started before the caudal migration of the aortic attachment of the ductus. Sympathetic nerve ganglia developed immediately posterior to both aortae, with a single embryonic specimen showing a large ganglion at the midline close to the union of the aortic arches. These ganglia may interfere with blood flow through the distal left arch, resulting in the ductus ending at the descending aorta behind the oesophagus. In another fetus examined, a midline shift of the ductus course resulted in the trachea curving posteriorly. Therefore, solitary right arch is likely to accompany abnormalities of the surrounding structures. The timing and site of the obstruction should be different between types: an almost midline obstruction near the aortic union needed for the development of the left-sided ductus and a distal obstruction near the left subclavian arterial origin needed for the development of the right-sided ductus. A mass effect of the sympathetic ganglia may explain the pathogenesis of any type of anomalous ductus arteriosus shown in previous reports of the solitary right arch.

The mechanical properties of the systemic and pulmonary arteries of Python regius correlate with blood pressures.

PubMed

van Soldt, Benjamin J; Danielsen, Carl Christian; Wang, Tobias

2015-12-01

Pythons are unique amongst snakes in having different pressures in the aortas and pulmonary arteries because of intraventricular pressure separation. In this study, we investigate whether this correlates with different blood vessel strength in the ball python Python regius. We excised segments from the left, right, and dorsal aortas, and from the two pulmonary arteries. These were subjected to tensile testing. We show that the aortic vessel wall is significantly stronger than the pulmonary artery wall in P. regius. Gross morphological characteristics (vessel wall thickness and correlated absolute amount of collagen content) are likely the most influential factors. Collagen fiber thickness and orientation are likely to have an effect, though the effect of collagen fiber type and cross-links between fibers will need further study. © 2015 Wiley Periodicals, Inc.

Preventive Role of Hilar Parasympathetic Ganglia on Pulmonary Artery Vasospasm in Subarachnoid Hemorrhage: An Experimental Study.

PubMed

Araz, Omer; Aydin, Mehmet Dumlu; Gundogdu, Betul; Altas, Ender; Cakir, Murteza; Calikoglu, Cagatay; Atalay, Canan; Gundogdu, Cemal

2015-01-01

Pulmonary arteries are mainly innervated by sympathetic vasoconstrictor and parasympathetic vasodilatory fibers. We examined whether there is a relationship between the neuron densities of hilar parasympathetic ganglia and pulmonary vasospasm in subarachnoid hemorrhage (SAH). Twenty-four rabbits were divided into two groups: control (n=8) and SAH (n=16). The animals were observed for 20 days following experimental SAH. The number of hilar parasympathetic ganglia and their neuron densities were determined. Proportion of pulmonary artery ring surface to lumen surface values was accepted as vasospasm index (VSI). Neuron densities of the hilar ganglia and VSI values were compared statistically. Animals in the SAH group experienced either mild (n=6) or severe (n=10) pulmonary artery vasospasm. In the control group, the mean VSI of pulmonary arteries was 0.777±0.048 and the hilar ganglion neuron density was estimated as 12.100±2.010/mm < sup > 3 < /sup > . In SAH animals with mild vasospasm, VSI=1.148±0.090 and neuron density was estimated as 10.110±1.430/mm < sup > 3 < /sup > ; in animals with severe vasospasm, VSI=1.500±0.120 and neuron density was estimated as 7.340±990/mm < sup > 3 < /sup > . There was an inverse correlation between quantity and neuron density of hilar ganglia and vasospasm index value. The low numbers and low density of hilar parasympathetic ganglia may be responsible for the more severe artery vasospasm in SAH.

Temperature measurement in intensive care patients: comparison of urinary bladder, oesophageal, rectal, axillary, and inguinal methods versus pulmonary artery core method.

PubMed

Lefrant, J-Y; Muller, L; de La Coussaye, J Emmanuel; Benbabaali, M; Lebris, C; Zeitoun, N; Mari, C; Saïssi, G; Ripart, J; Eledjam, J-J

2003-03-01

Comparisons of urinary bladder, oesophageal, rectal, axillary, and inguinal temperatures versus pulmonary artery temperature. Prospective cohort study. Intensive Care Unit of a University-Hospital. Forty-two intensive care patients requiring a pulmonary artery catheter (PAC). Patients requiring PAC and without oesophageal, urinary bladder, and/or rectal disease or recent surgery were included in the study. Temperature was simultaneously monitored with PAC, urinary, oesophageal, and rectal electronic thermometers and with axillary and inguinal gallium-in-glass thermometers. Comparisons used a Bland and Altman method. The pulmonary arterial temperature ranged from 33.7 degrees C to 40.2 degrees C. Urinary bladder temperature was assessed in the last 22 patients. A total of 529 temperature measurement comparisons were carried out (252 comparisons of esophageal, rectal, inguinal, axillary, and pulmonary artery temperature measurements in the first 20 patients, and 277 comparisons with overall methods in the last patients). Nine to 18 temperature measurement comparisons were carried out per patient (median = 13). The mean differences between pulmonary artery temperatures and those of the different methods studied were: oesophageal (0.11+/-0.30 degrees C), rectal (-0.07+/-0.40 degrees C), axillary (0.27+/-0.45 degrees C), inguinal (0.17+/-0.48 degrees C), urinary bladder (-0.21+/-0.20 degrees C). In critically ill patients, urinary bladder and oesophageal electronic thermometers are more reliable than the electronic rectal thermometer which is better than inguinal and axillary gallium-in-glass thermometers to measure core temperature.

Pulmonary artery occlusion pressure estimation by transesophageal echocardiography: is simpler better?

PubMed

Voga, Gorazd

2008-01-01

The measurement of pulmonary artery occlusion pressure (PAOP) is important for estimation of left ventricular filling pressure and for distinction between cardiac and non-cardiac etiology of pulmonary edema. Clinical assessment of PAOP, which relies on physical signs of pulmonary congestion, is uncertain. Reliable PAOP measurement can be performed by pulmonary artery catheter, but it is possible also by the use of echocardiography. Several Doppler variables show acceptable correlation with PAOP and can be used for its estimation in cardiac and critically ill patients. Noninvasive PAOP estimation should probably become an integral part of transthoracic and transesophageal echocardiographic evaluation in critically ill patients. However, the limitations of both methods should be taken into consideration, and in specific patients invasive PAOP measurement is still unavoidable, if the exact value of PAOP is needed.

Non-invasive estimation of pulmonary artery pressures in patients with sickle cell anaemia in Ibadan, Nigeria: an echocardiographic study.

PubMed

Enakpene, Evbu O; Adebiyi, Adewole A; Ogah, Okechukwu S; Olaniyi, John A; Aje, Akinyemi; Adeoye, Moshood A; Falase, Ayodele O

2014-10-01

Pulmonary hypertension is emerging as one of the causes of morbidity and mortality in adults with sickle cell disease. The prevalence of pulmonary hypertension in Nigerian adults with sickle cell anaemia is unknown. We decided to estimate the pulmonary artery systolic and diastolic pressures in subjects with sickle cell anaemia seen at the University College Hospital, Ibadan, Nigeria, and to determine the frequency of pulmonary hypertension among them. Ninety patients (38 males and 52 females) with sickle cell anaemia in steady state and comparable age- and sex-matched normal controls had a clinical evaluation and echocardiographic examination. The mean age of the subjects with sickle cell anaemia was 24.0 (9.00) years while the mean age for the control group was 24.0 (7.00) years. The frequency of pulmonary hypertension as assessed by a tricuspid regurgitant jet velocity of > 2.5 m/s in this study was 12.2%. Larger left ventricular dimensions and volumes, higher stroke volume and increased left ventricular mass indexed by body surface area were found to be associated with pulmonary hypertension. A multivariate analysis of the potential predictors of pulmonary hypertension in this study showed that male sex and lower packed cell volume (PCV) were independent predictors of pulmonary hypertension in patients with sickle cell anaemia. We conclude that pulmonary artery systolic and diastolic pressures are higher in subjects with sickle cell disease than normal controls. Male sex and low PCV are independent determinants of pulmonary arterial pressure in subjects with sickle cell anaemia in Nigeria.

Off-pump grafting does not reduce postoperative pulmonary dysfunction.

PubMed

Izzat, Mohammad Bashar; Almohammad, Farouk; Raslan, Ahmad Fahed

2017-02-01

Objectives Pulmonary dysfunction is a recognized postoperative complication that may be linked to use of cardiopulmonary bypass. The off-pump technique of coronary artery bypass aims to avoid some of the complications that may be related to cardiopulmonary bypass. In this study, we compared the influence of on-pump or off-pump coronary artery bypass on pulmonary gas exchange following routine surgery. Methods Fifty patients (mean age 60.4 ± 8.4 years) with no preexisting lung disease and good left ventricular function undergoing primary coronary artery bypass grafting were prospectively randomized to undergo surgery with or without cardiopulmonary bypass. Alveolar/arterial oxygen pressure gradients were calculated prior to induction of anesthesia while the patients were breathing room air, and repeated postoperatively during mechanical ventilation and after extubation while inspiring 3 specific fractions of oxygen. Results Baseline preoperative arterial blood gases and alveolar/arterial oxygen pressure gradients were similar in both groups. At both postoperative stages, the partial pressure of arterial oxygen and alveolar/arterial oxygen pressure gradients increased with increasing fraction of inspired oxygen, but there were no statistically significant differences between patients who underwent surgery with or without cardiopulmonary bypass, either during ventilation or after extubation. Conclusions Off-pump surgery is not associated with superior pulmonary gas exchange in the early postoperative period following routine coronary artery bypass grafting in patients with good left ventricular function and no preexisting lung disease.

Role of Transcription Factors in Pulmonary Artery Smooth Muscle Cells: An Important Link to Hypoxic Pulmonary Hypertension.

PubMed

Di Mise, Annarita; Wang, Yong-Xiao; Zheng, Yun-Min

2017-01-01

Hypoxia, namely a lack of oxygen in the blood, induces pulmonary vasoconstriction and vasoremodeling, which serve as essential pathologic factors leading to pulmonary hypertension (PH). The underlying molecular mechanisms are uncertain; however, pulmonary artery smooth muscle cells (PASMCs) play an essential role in hypoxia-induced pulmonary vasoconstriction, vasoremodeling, and PH. Hypoxia causes oxidative damage to DNAs, proteins, and lipids. This damage (oxidative stress) modulates the activity of ion channels and elevates the intracellular calcium concentration ([Ca 2+ ] i , Ca 2+ signaling) of PASMCs. The oxidative stress and increased Ca 2+ signaling mutually interact with each other, and synergistically results in a variety of cellular responses. These responses include functional and structural abnormalities of mitochondria, sarcoplasmic reticulum, and nucleus; cell contraction, proliferation, migration, and apoptosis, as well as generation of vasoactive substances, inflammatory molecules, and growth factors that mediate the development of PH. A number of studies reveal that various transcription factors (TFs) play important roles in hypoxia-induced oxidative stress, disrupted PAMSC Ca 2+ signaling and the development and progress of PH. It is believed that in the pathogenesis of PH, hypoxia facilitates these roles by mediating the expression of multiple genes. Therefore, the identification of specific genes and their transcription factors implicated in PH is necessary for the complete understanding of the underlying molecular mechanisms. Moreover, this identification may aid in the development of novel and effective therapeutic strategies for PH.

Maternal high-altitude hypoxia and suppression of ryanodine receptor-mediated Ca2+ sparks in fetal sheep pulmonary arterial myocytes

PubMed Central

Hadley, Scott R.; Blood, Quintin; Rubalcava, Monica; Waskel, Edith; Lumbard, Britney; Le, Petersen; Longo, Lawrence D.; Buchholz, John N.

2012-01-01

Ca2+ sparks are fundamental Ca2+ signaling events arising from ryanodine receptor (RyR) activation, events that relate to contractile and dilatory events in the pulmonary vasculature. Recent studies demonstrate that long-term hypoxia (LTH) can affect pulmonary arterial reactivity in fetal, newborn, and adult animals. Because RyRs are important to pulmonary vascular reactivity and reactivity changes with ontogeny and LTH we tested the hypothesis that RyR-generated Ca2+ signals are more active before birth and that LTH suppresses these responses. We examined these hypotheses by performing confocal imaging of myocytes in living arteries and by performing wire myography studies. Pulmonary arteries (PA) were isolated from fetal, newborn, or adult sheep that lived at low altitude or from those that were acclimatized to 3,801 m for > 100 days. Confocal imaging demonstrated preservation of the distance between the sarcoplasmic reticulum, nucleus, and plasma membrane in PA myocytes. Maturation increased global Ca2+ waves and Ca2+ spark activity, with sparks becoming larger, wider, and slower. LTH preferentially depressed Ca2+ spark activity in immature pulmonary arterial myocytes, and these sparks were smaller, wider, and slower. LTH also suppressed caffeine-elicited contraction in fetal PA but augmented contraction in the newborn and adult. The influence of both ontogeny and LTH on RyR-dependent cell excitability shed new light on the therapeutic potential of these channels for the treatment of pulmonary vascular disease in newborns as well as adults. PMID:22962012

New Insight from Using Spatiotemporal Image Correlation in Prenatal Screening of Fetal Conotruncal Defects

PubMed Central

Xie, Zuo-ping; Zhao, Bo-wen; Yuan, Hua; Hua, Qi-qi; Jin, She-hong; Shen, Xiao-yan; Han, Xin-hong; Zhou, Jia-mei; Fang, Min; Chen, Jin-hong

2013-01-01

Background: To establish the reference range of the angle between ascending aorta and main pulmonary artery of fetus in the second and third trimester using spatiotemporal image correlation (STIC), and to investigate the value of this angle in prenatal screening of conotruncal defects (CTDs). Materials and Methods: Volume images of 311 normal fetuses along with 20 fetuses with congenital heart diseases were recruited in this cross-sectional study. An offline analysis of acquired volume datasets was carried out with multiplanar mode. The angle between aorta and pulmonary artery was measured by navigating the pivot point and rotating axes and the reference range was established. The images of ascending aorta and main pulmonary artery in fetuses with congenital heart diseases were observed by rotating the axes within the normal angle reference range. Results: The angle between ascending aorta and main pulmonary artery of the normal fetus (range: 59.1˚~97.0˚, mean ± SD: 78.0˚ ± 9.7˚) was negatively correlated with gestational age (r = -0.52; p<0.01). By rotating the normal angle range corresponding to gestational age, the fetuses with CTD could not display views of their left ventricular long axis and main pulmonary trunk correctly. Conclusion: The left ventricular long axis and main pulmonary trunk views can be displayed using STIC so that the echocardiographic protocol of the cardiovascular joint could be standardized. The reference range of the angle between ascending aorta and main pulmonary artery is clinically useful in prenatal screening of CTD and provides a reliable quantitative standard to estimate the spatial relationship of the large arteries of fetus. PMID:24520485

STARS knockout attenuates hypoxia-induced pulmonary arterial hypertension by suppressing pulmonary arterial smooth muscle cell proliferation.

PubMed

Shi, Zhaoling; Wu, Huajie; Luo, Jianfeng; Sun, Xin

2017-03-01

STARS (STriated muscle Activator of Rho Signaling) is a sarcomeric protein, which expressed early in cardiac development and involved in pathological remodeling. Abundant evidence indicated that STARS could regulate cell proliferation, but it's exact function remains unclear. In this study, we aimed to investigate the role of STARS in the proliferation of pulmonary arterial smooth muscle cells (PASMC) and the potential effect on the progression of pulmonary arterial hypertension (PAH). In this study, we established a PAH mouse model through chronic hypoxia exposure as reflected by the increased RVSP and RVHI. Western blot and RT-qPCR detected the increased STARS protein and mRNA levels in PAH mice. Next, we cultured the primary PASMC from PAH mice. After STARS overexpression in PASMC, STARS, SRF and Egr-1 were up-regulated significantly. The MTT assay revealed an increase in cell proliferation. Flow cytometry showed a marked inhibition of cell apoptosis. However, STARS silence in PASMC exerted opposite effects with STARS overexpression. SRF siRNA transfection blocked the effects of STARS overexpression in PASMC. In order to further confirm the role of STARS in PAH mice in vivo, we exposed STARS knockout mice to hypoxia and found lower RVSP and RVHI in knockout mice as compared with controls. Our results not only suggest that STARS plays a crucial role in the development of PAH by increasing the proliferation of PASMC through activation of the SRF/Egr-1 pathway, but also provides a new mechanism for hypoxia-induced PAH. In addition, STARS may represent a potential treatment target. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Pulmonary vascular dysfunction in ARDS

PubMed Central

2014-01-01

Acute respiratory distress syndrome (ARDS) is characterised by diffuse alveolar damage and is frequently complicated by pulmonary hypertension (PH). Multiple factors may contribute to the development of PH in this setting. In this review, we report the results of a systematic search of the available peer-reviewed literature for papers that measured indices of pulmonary haemodynamics in patients with ARDS and reported on mortality in the period 1977 to 2010. There were marked differences between studies, with some reporting strong associations between elevated pulmonary arterial pressure or elevated pulmonary vascular resistance and mortality, whereas others found no such association. In order to discuss the potential reasons for these discrepancies, we review the physiological concepts underlying the measurement of pulmonary haemodynamics and highlight key differences between the concepts of resistance in the pulmonary and systemic circulations. We consider the factors that influence pulmonary arterial pressure, both in normal lungs and in the presence of ARDS, including the important effects of mechanical ventilation. Pulmonary arterial pressure, pulmonary vascular resistance and transpulmonary gradient (TPG) depend not alone on the intrinsic properties of the pulmonary vascular bed but are also strongly influenced by cardiac output, airway pressures and lung volumes. The great variability in management strategies within and between studies means that no unified analysis of these papers was possible. Uniquely, Bull et al. (Am J Respir Crit Care Med 182:1123–1128, 2010) have recently reported that elevated pulmonary vascular resistance (PVR) and TPG were independently associated with increased mortality in ARDS, in a large trial with protocol-defined management strategies and using lung-protective ventilation. We then considered the existing literature to determine whether the relationship between PVR/TPG and outcome might be causal. Although we could identify potential mechanisms for such a link, the existing evidence does not allow firm conclusions to be drawn. Nonetheless, abnormally elevated PVR/TPG may provide a useful index of disease severity and progression. Further studies are required to understand the role and importance of pulmonary vascular dysfunction in ARDS in the era of lung-protective ventilation. PMID:25593744

Coronary Artery Anomalies in Animals

PubMed Central

Scansen, Brian A.

2017-01-01

Coronary artery anomalies represent a disease spectrum from incidental to life-threatening. Anomalies of coronary artery origin and course are well-recognized in human medicine, but have received limited attention in veterinary medicine. Coronary artery anomalies are best described in the dog, hamster, and cow though reports also exist in the horse and pig. The most well-known anomaly in veterinary medicine is anomalous coronary artery origin with a prepulmonary course in dogs, which limits treatment of pulmonary valve stenosis. A categorization scheme for coronary artery anomalies in animals is suggested, dividing these anomalies into those of major or minor clinical significance. A review of coronary artery development, anatomy, and reported anomalies in domesticated species is provided and four novel canine examples of anomalous coronary artery origin are described: an English bulldog with single left coronary ostium and a retroaortic right coronary artery; an English bulldog with single right coronary ostium and transseptal left coronary artery; an English bulldog with single right coronary ostium and absent left coronary artery with a prepulmonary paraconal interventricular branch and an interarterial circumflex branch; and a mixed-breed dog with tetralogy of Fallot and anomalous origin of all coronary branches from the brachiocephalic trunk. Coronary arterial fistulae are also described including a coronary cameral fistula in a llama cria and an English bulldog with coronary artery aneurysm and anomalous shunting vessels from the right coronary artery to the pulmonary trunk. These examples are provided with the intent to raise awareness and improve understanding of such defects. PMID:29056679

Spironolactone Therapy in Chronic Stable Right HF Trial

ClinicalTrials.gov

2018-04-12

Chronic Right-Sided Heart Failure; Pulmonary Arterial Hypertension; Pulmonary Hypertension, Primary, 2; Pulmonary Hypertension, Primary, 3; Pulmonary Hypertension, Primary, 4; Cardiomyopathy Right Ventricular

Rare presentation of intralobar pulmonary sequestration associated with repeated episodes of ventricular tachycardia

PubMed Central

Rao, D Sheshagiri; Barik, Ramachandra

2016-01-01

Arterial supply of an intralobar pulmonary sequestration (IPS) from the coronary circulation is extremely rare. A significant coronary steal does not occur because of dual or triple sources of blood supply to sequestrated lung tissue. We present a 60-year-old woman who presented to us with repeated episodes of monomorphic ventricular tachycardia (VT) in last 3 mo. Radio frequency ablation was ineffective. On evaluation, she had right lower lobe IPS with dual arterial blood supply, i.e., right pulmonary artery and the systemic arterial supply from the right coronary artery (RCA). Stress myocardial perfusion scan revealed significant inducible ischemia in the RCA territory. Coronary angiogram revealed critical stenosis of proximal RCA just after the origin of the systemic artery supplying IPS. The critical stenosis in the RCA was stented. At 12 mo follow-up, she had no further episodes of VT or angina. PMID:27468336

Rare presentation of intralobar pulmonary sequestration associated with repeated episodes of ventricular tachycardia.

PubMed

Rao, D Sheshagiri; Barik, Ramachandra

2016-07-26

Arterial supply of an intralobar pulmonary sequestration (IPS) from the coronary circulation is extremely rare. A significant coronary steal does not occur because of dual or triple sources of blood supply to sequestrated lung tissue. We present a 60-year-old woman who presented to us with repeated episodes of monomorphic ventricular tachycardia (VT) in last 3 mo. Radio frequency ablation was ineffective. On evaluation, she had right lower lobe IPS with dual arterial blood supply, i.e., right pulmonary artery and the systemic arterial supply from the right coronary artery (RCA). Stress myocardial perfusion scan revealed significant inducible ischemia in the RCA territory. Coronary angiogram revealed critical stenosis of proximal RCA just after the origin of the systemic artery supplying IPS. The critical stenosis in the RCA was stented. At 12 mo follow-up, she had no further episodes of VT or angina.

Cardio-Pulmonary Response to Shock.

DTIC Science & Technology

1979-12-01

increased 0.6 L/min (p < .05). These results indicate that local surgical trauma can stimulate the pulmonary secretion of PGI 2 to levels that have been... pulmonary metabolic changes induced by PEEP and examines the influence of the latter on hemodynmics. Experiments were conducted in 25 isolated, temperature...arterial pressure (MAP) from 113 ± 17 to 100 ± 26 mm Hg (p < .01). PEEP yielded no change in C0 or MAP in Group III. Pulse, pulmonary arterial wedge

World Health Organization Group I Pulmonary Hypertension: Epidemiology and Pathophysiology.

PubMed

Prins, Kurt W; Thenappan, Thenappan

2016-08-01

Pulmonary arterial hypertension (PAH) is a debilitating disease characterized by pathologic remodeling of the resistance pulmonary arteries, ultimately leading to right ventricular (RV) failure and death. In this article we discuss the definition of PAH, the initial epidemiology based on the National Institutes of Health Registry, and the updated epidemiology gleaned from contemporary registries, pathogenesis of pulmonary vascular dysfunction and proliferation, and RV failure in PAH. Copyright © 2016 Elsevier Inc. All rights reserved.

Bronchial Artery Embolization in the Management of Pulmonary Parenchymal Endometriosis with Hemoptysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kervancioglu, Selim, E-mail: skervancioglu@yahoo.com; Andic, Cagatay; Bayram, Nazan

Pulmonary parenchymal endometriosis is extremely rare and usually manifests itself with a recurrent hemoptysis associated with the menstrual cycle. The therapies proposed for women with endometriosis consist of medical treatments and surgery. Bronchial artery embolization has become a well-established and minimally invasive treatment modality for hemoptysis, and to the best of our knowledge, it has not been reported in pulmonary endometriosis. We report a case of pulmonary parenchymal endometriosis treated with embolotheraphy for hemoptysis.

A case of pulmonary hemorrhage due to drug-induced pneumonitis secondary to ticagrelor therapy.

PubMed

Whitmore, Timothy J; O'Shea, John P; Starac, Diana; Edwards, Mark G; Waterer, Grant W

2014-03-01

We report a case of significant pulmonary hemorrhage developing shortly after commencing ticagrelor and aspirin therapy and requiring coronary artery bypass grafting to safely cease the antiplatelet therapy. Lung biopsy findings were consistent with drug-induced lung injury. Clinicians should be aware of this significant adverse event with this drug class.

Dysfunctional BMPR2 signaling drives an abnormal endothelial requirement for glutamine in pulmonary arterial hypertension.

PubMed

Egnatchik, Robert A; Brittain, Evan L; Shah, Amy T; Fares, Wassim H; Ford, H James; Monahan, Ken; Kang, Christie J; Kocurek, Emily G; Zhu, Shijun; Luong, Thong; Nguyen, Thuy T; Hysinger, Erik; Austin, Eric D; Skala, Melissa C; Young, Jamey D; Roberts, L Jackson; Hemnes, Anna R; West, James; Fessel, Joshua P

2017-03-01

Pulmonary arterial hypertension (PAH) is increasingly recognized as a systemic disease driven by alteration in the normal functioning of multiple metabolic pathways affecting all of the major carbon substrates, including amino acids. We found that human pulmonary hypertension patients (WHO Group I, PAH) exhibit systemic and pulmonary-specific alterations in glutamine metabolism, with the diseased pulmonary vasculature taking up significantly more glutamine than that of controls. Using cell culture models and transgenic mice expressing PAH-causing BMPR2 mutations, we found that the pulmonary endothelium in PAH shunts significantly more glutamine carbon into the tricarboxylic acid (TCA) cycle than wild-type endothelium. Increased glutamine metabolism through the TCA cycle is required by the endothelium in PAH to survive, to sustain normal energetics, and to manifest the hyperproliferative phenotype characteristic of disease. The strict requirement for glutamine is driven by loss of sirtuin-3 (SIRT3) activity through covalent modification by reactive products of lipid peroxidation. Using 2-hydroxybenzylamine, a scavenger of reactive lipid peroxidation products, we were able to preserve SIRT3 function, to normalize glutamine metabolism, and to prevent the development of PAH in BMPR2 mutant mice. In PAH, targeting glutamine metabolism and the mechanisms that underlie glutamine-driven metabolic reprogramming represent a viable novel avenue for the development of potentially disease-modifying therapeutics that could be rapidly translated to human studies.

Anomalous origin of left coronary artery from pulmonary artery in older children and adults: direct aortic implantation.

PubMed

Kottayil, Brijesh P; Jayakumar, Karunakaran; Dharan, Baiju S; Pillai, Vivek V; Ajitkumar, Valaparambil; Menon, Sabarinath; Sanjay, Ganapathi

2011-02-01

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) presents rarely in adulthood and is treated by different surgical techniques with varying results. This study was undertaken to evaluate the feasibility of reestablishment of a dual coronary system in older children and adults with emphasis on direct aortic implantation. From 2002 to 2010, 10 patients aged 10 to 51 years (median age, 24 years) underwent surgical correction of ALCAPA. Median weight was 44.5 kg. All the patients except 2 were symptomatic. Two patients were in atrial fibrillation. Eight patients had varying degrees of mitral regurgitation, which was severe in 2. In all patients, the left coronary artery was arising from the facing sinus of the pulmonary artery. Direct left main coronary implantation into the aorta was feasible in all patients. Mitral valve replacement was done in 4 patients. At a median follow-up of 5.5 years there was no new angina or infarction. One patient died 3 months postsurgery due to intracerebral bleed. Echocardiography demonstrated normal antegrade flow in the transferred left coronary artery, with 2 patients having persistent moderate mitral regurgitation. Coronary angiography done on follow-up in one patient revealed a patent transferred left coronary artery with distal development of new atherosclerotic lesion. Direct reimplantation of the ALCAPA is considered technically more difficult and hazardous in adults. With increased experience with coronary transfer technique, direct aortic implantation is feasible in adult cases. This provides a more physiologic correction and reestablishment of a dual coronary system with a better outcome. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Molecular Analysis of BMPR2, TBX4, and KCNK3 and Genotype-Phenotype Correlations in Spanish Patients and Families With Idiopathic and Hereditary Pulmonary Arterial Hypertension.

PubMed

Navas, Paula; Tenorio, Jair; Quezada, Carlos Andrés; Barrios, Elvira; Gordo, Gema; Arias, Pedro; López Meseguer, Manuel; Santos-Lozano, Alejandro; Palomino Doza, Julian; Lapunzina, Pablo; Escribano Subías, Pilar

2016-11-01

Recent advances in genetics have led to the discovery of new genes associated with pulmonary arterial hypertension, such as TBX4 and KCNK3. The phenotype and prognosis associated with these new genes have been scarcely described and their role in the Spanish population is unknown. The aim of this study was to characterize the genetics of a Spanish cohort of patients with idiopathic and hereditary pulmonary arterial hypertension and to describe the phenotype and prognostic factors associated with BMPR2 and the new genes (KCNK3 and TBX4). A total of 165 adult patients were screened for BMPR2, KCNK3, and TBX4 mutations, 143 with idiopathic pulmonary arterial hypertension and 22 with hereditary pulmonary arterial hypertension. Baseline characteristics and survival were compared among the different subgroups and predictors of poor outcomes were analyzed. We also performed family screening. The genetic study identified a possibly associated mutation in 11.10% of the idiopathic cases (n = 16) and in 68.18% of the hereditary cases (n = 15). There were 19 mutations in BMPR2, 4 in TBX4, and 3 in KCNK3. The forms associated with TBX4 showed the highest survival rate (P < .01). Advanced functional class at diagnosis was the only factor associated with poor outcomes in the hereditary forms. In the family screening, 37.5% of relatives tested positive. The genetics of pulmonary arterial hypertension in the Spanish population may differ from other populations, with a lower proportion of BMPR2 causative mutations. In our cohort, TBX4-related forms of pulmonary arterial hypertension showed a more benign course and late diagnosis was the only predictor of adverse outcomes in the hereditary forms of the disease. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Clinical and imaging features of pulmonary artery sling in infants without significant hemodynamic changes.

PubMed

Wang, Jian-Hua; Ding, Gui-Chun; Zhang, Min-Yu; Liu, Mei; Niu, Hai-Yan

2011-10-01

Pulmonary artery sling (PAS) is a rare congenital heart anomaly and may cause unexplained respiratory symptoms in infants. Since the non-specific respiratory symptoms of PAS may lead to misdiagnosis, the aim of this study was to clarify the clinical and imaging features of this disease for timely diagnosis and treatment. Clinical histories, physical examinations and imaging studies were retrospectively evaluated in nine infants with PAS. Chest X-ray, echocardiography and contrast-enhanced computed tomography (CT) with 3-dimensional reconstructions were performed in all patients and three of them received surgical treatment. Nine cases included six males and three females with a mean age of (4.3 ± 2.8) months ranging from 2 to 11 months old. All patients had respiratory symptoms including recurrent cough, stridor and wheezing. The onset of symptoms was within 3 months in all cases and three children had symptoms only a few days after birth. The chest X-ray showed pneumonia in all cases. Contrast-enhanced CT showed the tracheal compression at different lengths in every case. The echocardiograph findings of PAS were anomalous origins of the left pulmonary artery from the posterior aspect of the right pulmonary artery. Of the 9 cases, 8 cases were diagnosed correctly by echocardiography. Of the complicated abnormalities, there were one with secundum atrial septal defect, one with patent foramen ovale and three with persistent left superior vena cava. None of them were complicated with significant blood dynamic changes. Infants with recurrent respiratory symptoms such as chronic cough, stridor and wheezing, should be examined for the possible presence of congenital pulmonary artery sling. As a noninvasive technique, echocardiography is very helpful and should be the first-choice modality for the diagnosis of pulmonary artery sling. Contrast-enhanced CT, clearly demonstrating the anatomy of pulmonary artery sling and the position and extent of trachea compression, is necessary for the final diagnosis and pre-operation evaluation.

Key Role of ROS in the Process of 15-Lipoxygenase/15-Hydroxyeicosatetraenoiccid-Induced Pulmonary Vascular Remodeling in Hypoxia Pulmonary Hypertension

PubMed Central

Qiu, Yanli; Liu, Gaofeng; Sheng, Tingting; Yu, Xiufeng; Wang, Shuang; Zhu, Daling

2016-01-01

We previously reported that 15-lipoxygenase (15-LO) and its metabolite 15-hydroxyeicosatetraenoic acid (15-HETE) were up-regulated in pulmonary arterial cells from both pulmonary artery hypertension patients and hypoxic rats and that these factors mediated the progression of pulmonary hypertension (PH) by affecting the proliferation and apoptosis of pulmonary arterial (PA) cells. However, the underlying mechanisms of the remodeling induced by 15-HETE have remained unclear. As reactive oxygen species (ROS) and 15-LO are both induced by hypoxia, it is possible that ROS are involved in the events of hypoxia-induced 15-LO expression that lead to PH. We employed immunohistochemistry, tube formation assays, bromodeoxyuridine (BrdU) incorporation assays, and cell cycle analyses to explore the role of ROS in the process of 15-HETE-mediated hypoxic pulmonary hypertension (HPH). We found that exogenous 15-HETE facilitated the generation of ROS and that this effect was mainly localized to mitochondria. In particular, the mitochondrial electron transport chain and nicotinamide-adenine dinucleotide phosphate oxidase 4 (Nox4) were responsible for the significant 15-HETE-stimulated increase in ROS production. Moreover, ROS induced by 15-HETE stimulated endothelial cell (EC) migration and promoted pulmonary artery smooth muscle cell (PASMC) proliferation under hypoxia via the p38 MAPK pathway. These results indicated that 15-HETE-regulated ROS mediated hypoxia-induced pulmonary vascular remodeling (PVR) via the p38 MAPK pathway. PMID:26871724

The pathophysiology of pulmonary hypertension in left heart disease.

PubMed

Breitling, Siegfried; Ravindran, Krishnan; Goldenberg, Neil M; Kuebler, Wolfgang M

2015-11-01

Pulmonary hypertension (PH) is characterized by elevated pulmonary arterial pressure leading to right-sided heart failure and can arise from a wide range of etiologies. The most common cause of PH, termed Group 2 PH, is left-sided heart failure and is commonly known as pulmonary hypertension with left heart disease (PH-LHD). Importantly, while sharing many clinical features with pulmonary arterial hypertension (PAH), PH-LHD differs significantly at the cellular and physiological levels. These fundamental pathophysiological differences largely account for the poor response to PAH therapies experienced by PH-LHD patients. The relatively high prevalence of this disease, coupled with its unique features compared with PAH, signal the importance of an in-depth understanding of the mechanistic details of PH-LHD. The present review will focus on the current state of knowledge regarding the pathomechanisms of PH-LHD, highlighting work carried out both in human trials and in preclinical animal models. Adaptive processes at the alveolocapillary barrier and in the pulmonary circulation, including alterations in alveolar fluid transport, endothelial junctional integrity, and vasoactive mediator secretion will be discussed in detail, highlighting the aspects that impact the response to, and development of, novel therapeutics. Copyright © 2015 the American Physiological Society.

Fatal persistent pulmonary hypertension presenting late in the neonatal period.

PubMed Central

Raine, J; Hislop, A A; Redington, A N; Haworth, S G; Shinebourne, E A

1991-01-01

Two cases of fatal idiopathic persistent pulmonary hypertension presented late in the neonatal period. Lungs were examined histologically by light and electron microscopy, and immunocytochemical studies were used to identify nerves. There was extension of medial smooth muscle distally along the arterial pathway so that most precapillary arteries had completely muscular walls, which in some cases completely obliterated the vessel lumen. Enlarged endothelial cells also contributed to the reduction in the size of the lumen. Nerve fibres accompanying muscular arteries were found in the alveolar region, more distal than is normal. The predominant neuropeptide was the vasoconstrictor tyrosine. Possible aetiological factors in persistent pulmonary hypertension of the newborn are increased muscularity of the peripheral pulmonary arteries antenatally, an increase in the number of vasoconstrictor nerves, or an imbalance in the production of leukotrienes and prostacyclins in the perinatal period. Images Figure 1 Figure 2 Figure 3 PMID:2025031

System for definition of the central-chest vasculature

NASA Astrophysics Data System (ADS)

Taeprasartsit, Pinyo; Higgins, William E.

2009-02-01

Accurate definition of the central-chest vasculature from three-dimensional (3D) multi-detector CT (MDCT) images is important for pulmonary applications. For instance, the aorta and pulmonary artery help in automatic definition of the Mountain lymph-node stations for lung-cancer staging. This work presents a system for defining major vascular structures in the central chest. The system provides automatic methods for extracting the aorta and pulmonary artery and semi-automatic methods for extracting the other major central chest arteries/veins, such as the superior vena cava and azygos vein. Automatic aorta and pulmonary artery extraction are performed by model fitting and selection. The system also extracts certain vascular structure information to validate outputs. A semi-automatic method extracts vasculature by finding the medial axes between provided important sites. Results of the system are applied to lymph-node station definition and guidance of bronchoscopic biopsy.

Aorta and pulmonary artery segmentation using optimal surface graph cuts in non-contrast CT

NASA Astrophysics Data System (ADS)

Sedghi Gamechi, Zahra; Arias-Lorza, Andres M.; Pedersen, Jesper Holst; de Bruijne, Marleen

2018-03-01

Accurate measurements of the size and shape of the aorta and pulmonary arteries are important as risk factors for cardiovascular diseases, and for Chronicle Obstacle Pulmonary Disease (COPD).1 The aim of this paper is to propose an automated method for segmenting the aorta and pulmonary arteries in low-dose non-ECGgated non-contrast CT scans. Low contrast and the high noise level make the automatic segmentation in such images a challenging task. In the proposed method, first, a minimum cost path tracking algorithm traces the centerline between user-defined seed points. The cost function is based on a multi-directional medialness filter and a lumen intensity similarity metric. The vessel radius is also estimated from the medialness filter. The extracted centerlines are then smoothed and dilated non-uniformly according to the extracted local vessel radius and subsequently used as initialization for a graph-cut segmentation. The algorithm is evaluated on 225 low-dose non-ECG-gated non-contrast CT scans from a lung cancer screening trial. Quantitatively analyzing 25 scans with full manual annotations, we obtain a dice overlap of 0.94+/-0.01 for the aorta and 0.92+/-0.01 for pulmonary arteries. Qualitative validation by visual inspection on 200 scans shows successful segmentation in 93% of all cases for the aorta and 94% for pulmonary arteries.

Combined use of ursodeoxycholic acid and bosentan prevents liver toxicity caused by endothelin receptor antagonist bosentan monotherapy: two case reports.

PubMed

Ito, Tomoki; Ozaki, Yoshio; Son, Yonsu; Nishizawa, Tohru; Amuro, Hideki; Tanaka, Akihiro; Tamaki, Takeshi; Nomura, Shosaku

2014-07-11

Pulmonary arterial hypertension is a fatal disease characterized by progressive remodeling of the pulmonary arteries and an increase in pulmonary vascular resistance. Up to 50% of patients with systemic sclerosis have pulmonary arterial hypertension, which significantly affects the prognosis. The endothelin receptor antagonist bosentan is used for the treatment of pulmonary arterial hypertension and shows a great beneficial effect. However, the most frequent side effect of bosentan is liver toxicity, which often requires dose reduction and discontinuation. We report two cases (a 64-year-old Japanese woman and a 69-year old Japanese woman) of systemic sclerosis, both with severe Raynaud's phenomenon and pulmonary arterial hypertension. Both patients had initially received bosentan monotherapy, which caused liver toxicity as indicated by increased levels of alanine aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase. After dose reduction or discontinuation of bosentan, these liver function abnormalities were normalized and the patients subsequently received retreatment with a combination of bosentan and ursodeoxycholic acid. The results of liver function tests did not show any abnormalities after this combination therapy. These reports suggest the usefulness of ursodeoxycholic acid for preventing liver toxicity caused by bosentan. Thus, the addition of ursodeoxycholic acid to the treatment protocol is expected to be useful when liver toxicity emerges as a side effect of bosentan.

Suture Embolism of the Left Superior Lobar Pulmonary Artery.

PubMed

Ahn, Janice Seulgy; Grise, Joy; DelTondo, Joseph A

2018-05-31

Endogenous pulmonary thromboemboli are a common cause of noncardiac sudden natural death. Embolism of exogenous material is a rare but potential finding in autopsies following surgeries, medical procedures, penetrating trauma, and nonparenteral drug abuse. This report describes the first case of a suture embolism of the left superior lobar pulmonary artery following complicated abdominal surgery. © 2018 American Academy of Forensic Sciences.

Design of a hydraulic analog of the circulatory system for evaluating artificial hearts.

PubMed

Donovan, F M

1975-01-01

A major problem in improving artificial heart designs is the absence of methods for accurate in vitro testing of artificial heart systems. A mock circulatory system has been constructed which hydraulically simulates the systemic and pulmonary circulations of the normal human. The device is constructed of 1/2 in. acrylic sheet and has overall dimensions of 24 in. wide, 16 in. tall, and 8 in. deep. The artificial heart to be tested is attached to the front of the device, and pumps fluid from the systemic venous chamber into the pulmonary arterial chamber and from the pulmonary venous chamber into the systemic arterial chamber. Each of the four chambers is hermetically sealed. The compliance of each chamber is determined by the volume of air trapped above the fluid in that chamber. The pulmonary and systemic resistances are set automatically by bellows-operated valves to simulate the barroreceptor response in the systemic arteries and the passive pulmonary resistance response in the pulmonary arteries. Cardiac output is measured by a turbine flowmeter in the systemic circulation. Results using the Kwan-Gett artificial heart show a good comparison between the mock circulatory system response and the calf response.

Predictive role of arterial carboxyhemoglobin concentrations in ovine burn and smoke inhalation-induced lung injury.

PubMed

Lange, Matthias; Cox, Robert A; Enkhbaatar, Perenlei; Whorton, Elbert B; Nakano, Yoshimitsu; Hamahata, Atsumori; Jonkam, Collette; Esechie, Aimalohi; von Borzyskowski, Sanna; Traber, Lillian D; Traber, Daniel L

2011-05-01

Inhalation injury frequently occurs in burn patients and contributes to the morbidity and mortality of these injuries. Arterial carboxyhemoglobin has been proposed as an indicator of the severity of inhalation injury; however, the interrelation between arterial carboxyhemoglobin and histological alterations has not yet been investigated. Chronically instrumented sheep were subjected to a third degree burn of 40% of the total body surface area and inhalation of 48 breaths of cotton smoke. Carboxyhemoglobin was measured immediately after injury and correlated to clinical parameters of pulmonary function as well as histopathology scores from lung tissue harvested 24 hours after the injury. The injury was associated with a significant decline in pulmonary oxygenation and increases in pulmonary shunting, lung lymph flow, wet/dry weight ratio, congestion score, edema score, inflammation score, and airway obstruction scores. Carboxyhemoglobin was negatively correlated to pulmonary oxygenation and positively correlated to pulmonary shunting, lung lymph flow, and lung wet/dry weight ratio. No significant correlations could be detected between carboxyhemoglobin and histopathology scores and airway obstruction scores. Arterial carboxyhemoglobin in sheep with combined burn and inhalation injury are correlated with the degree of pulmonary failure and edema formation, but not with certain histological alterations including airway obstruction scores.

Pulmonary artery occlusion pressure estimation by transesophageal echocardiography: is simpler better?

PubMed Central

Voga, Gorazd

2008-01-01

The measurement of pulmonary artery occlusion pressure (PAOP) is important for estimation of left ventricular filling pressure and for distinction between cardiac and non-cardiac etiology of pulmonary edema. Clinical assessment of PAOP, which relies on physical signs of pulmonary congestion, is uncertain. Reliable PAOP measurement can be performed by pulmonary artery catheter, but it is possible also by the use of echocardiography. Several Doppler variables show acceptable correlation with PAOP and can be used for its estimation in cardiac and critically ill patients. Noninvasive PAOP estimation should probably become an integral part of transthoracic and transesophageal echocardiographic evaluation in critically ill patients. However, the limitations of both methods should be taken into consideration, and in specific patients invasive PAOP measurement is still unavoidable, if the exact value of PAOP is needed. PMID:18394183

Echinacoside induces rat pulmonary artery vasorelaxation by opening the NO-cGMP-PKG-BKCa channels and reducing intracellular Ca2+ levels

PubMed Central

Gai, Xiang-yun; Wei, Yu-hai; Zhang, Wei; Wuren, Ta-na; Wang, Ya-ping; Li, Zhan-qiang; Liu, Shou; Ma, Lan; Lu, Dian-xiang; Zhou, Yi; Ge, Ri-li

2015-01-01

Aim: Sustained pulmonary vasoconstriction as experienced at high altitude can lead to pulmonary hypertension (PH). The main purpose of this study is to investigate the vasorelaxant effect of echinacoside (ECH), a phenylethanoid glycoside from the Tibetan herb Lagotis brevituba Maxim and Cistanche tubulosa, on the pulmonary artery and its potential mechanism. Methods: Pulmonary arterial rings obtained from male Wistar rats were suspended in organ chambers filled with Krebs-Henseleit solution, and isometric tension was measured using a force transducer. Intracellular Ca2+ levels were measured in cultured rat pulmonary arterial smooth muscle cells (PASMCs) using Fluo 4-AM. Results: ECH (30–300 μmol/L) relaxed rat pulmonary arteries precontracted by noradrenaline (NE) in a concentration-dependent manner, and this effect could be observed in both intact endothelium and endothelium-denuded rings, but with a significantly lower maximum response and a higher EC50 in endothelium-denuded rings. This effect was significantly blocked by L-NAME, TEA, and BaCl2. However, IMT, 4-AP, and Gli did not inhibit ECH-induced relaxation. Under extracellular Ca2+-free conditions, the maximum contraction was reduced to 24.54%±2.97% and 10.60%±2.07% in rings treated with 100 and 300 μmol/L of ECH, respectively. Under extracellular calcium influx conditions, the maximum contraction was reduced to 112.42%±7.30%, 100.29%±8.66%, and 74.74%±4.95% in rings treated with 30, 100, and 300 μmol/L of ECH, respectively. After cells were loaded with Fluo 4-AM, the mean fluorescence intensity was lower in cells treated with ECH (100 μmol/L) than with NE. Conclusion: ECH suppresses NE-induced contraction of rat pulmonary artery via reducing intracellular Ca2+ levels, and induces its relaxation through the NO-cGMP pathway and opening of K+ channels (BKCa and KIR). PMID:25864652

In vitro evaluation of physiological spiral anastomoses for the arterial switch operation in simple transposition of the great arteries: a first step towards a surgical alternative?

PubMed

Sievers, Hans-Hinrich; Scharfschwerdt, Michael; Putman, Léon M

2015-08-01

The currently most frequently used technique for the arterial switch operation (ASO) in simple transposition of the great arteries (TGA) includes the transposition of the pulmonary artery anterior to the ascending aorta. This arterial arrangement is less anatomical, and although the initial results are excellent, some long-term data are indicating a certain risk of morbidity, encouraging the search for more physiological techniques. As a first step, we studied the feasibility of anatomical spiral anastomoses of the great vessels in vitro. A TGA model was constructed to simulate the different spatial positions of the great arteries followed by ASO with physiological spiral connections of the great arteries. It was possible to perform a physiological spiral connection of the great arteries without tension or torsion when the roots of the great vessels were arranged anterior-posterior and with up to 35° rotation of the aortic root to the right around the pulmonary root. With further rotation of the aorta, patch plasties were required for pulmonary artery elongation. The maximal width of the patch was 5 mm. In this TGA model, it was possible to perform tension- and torsion-free arterial anastomoses for ASO without artificial material, when the aortic root was positioned from 0° up to 35° to the right of the pulmonary root. Evaluation of coronary transfer is the next step. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Monitoring mixed venous oxygen saturation in patients with obstructive shock after massive pulmonary embolism.

PubMed

Krivec, Bojan; Voga, Gorazd; Podbregar, Matej

2004-05-31

Patients with massive pulmonary embolism and obstructive shock usually require hemodynamic stabilization and thrombolysis. Little is known about the optimal and proper use of volume infusion and vasoactive drugs, or about the titration of thrombolytic agents in patients with relative contraindication for such treatment. The aim of the study was to find the most rapidly changing hemodynamic variable to monitor and optimize the treatment of patients with obstructive shock following massive pulmonary embolism. Ten consecutive patients hospitalized in the medical intensive care unit in the community General Hospital with obstructive shock following massive pulmonary embolism were included in the prospective observational study. Heart rate, systolic arterial pressure, central venous pressure, mean pulmonary-artery pressure, cardiac index, total pulmonary vascular-resistance index, mixed venous oxygen saturation, and urine output were measured on admission and at 1, 2, 3, 4, 8, 12, and 16 hours. Patients were treated with urokinase through the distal port of a pulmonary-artery catheter. At 1 hour, mixed venous oxygen saturation, systolic arterial pressure and cardiac index were higher than their admission values (31+/-10 vs. 49+/-12%, p<0.0001; 86+/-12 vs. 105+/-17 mmHg, p<0.01; 1.5+/-0.4 vs. 1.9+/-0.7 L/min/m2, p<0.05; respectively), whereas heart rate, central venous pressure, mean pulmonary-artery pressure and urine output remained unchanged. Total pulmonary vascular-resistance index was lower than at admission (29+/-10 vs. 21+/-12 mmHg/L/min/m2, p<0.05). The relative change of mixed venous oxygen saturation at hour 1 was higher than the relative changes of all other studied variables (p<0.05). Serum lactate on admission and at 12 hours correlated to mixed venous oxygen saturation (r=-0.855, p<0.001). In obstructive shock after massive pulmonary embolism, mixed venous oxygen saturation changes more rapidly than other standard hemodynamic variables.

[Pulmonary thromboendarterectomy].

PubMed

Lausberg, H F; Tscholl, D; Schäfers, H-J

2004-08-01

Chronic thromboembolic pulmonary hypertension with concomitant right heart failure may develop as a sequela of acute pulmonary embolism with organization instead of thrombolysis of intravascular clots. Medical therapy aims at prevention of recurrent embolism by anticoagulation and vascular remodelling using vasodilator therapy. Lung transplantation or combined heart-lung transplantation is associated with unsatisfactory long-term results and comorbidity and therefore remains justified only in selected patients. Pulmonary thromboendarterectomy allows specific treatment of intravascular obstruction. This closed endarterectomy of the pulmonary arteries requires deep hypothermic circulatory arrest and can be performed with a perioperative mortality of less than 10%. The procedure significantly decreases pulmonary vascular resistance and often normalizes pulmonary hemodynamics and gas exchange. Postoperatively the patients' clinical condition improves and the majority have normal exercise capacity and activity.

Hemodynamic heterogeneity of connective tissue disease patients with borderline mean pulmonary artery pressure and its distinctive characters from those with normal pulmonary artery pressure: a retrospective study.

PubMed

Asari, Yusa; Yamasaki, Yoshioki; Tsuchida, Kosei; Suzuki, Kengo; Akashi, Yoshihiro J; Okazaki, Takahiro; Ozaki, Shoichi; Yamada, Hidehiro; Kawahata, Kimito

2018-05-18

To clarify whether patients with connective tissue disease (CTD)-associated borderline mean pulmonary artery pressure (mPAP) have distinctive hemodynamic characteristics from those with normal mPAP and whether pathogenesis is as heterogeneous as manifest pulmonary hypertension (PH). Seventy-five CTD patients who underwent right heart catheterization (RHC) from 2008 through 2016 were retrospectively analyzed. We compared between-group differences in clinical and hemodynamic findings: normal mPAP (n = 35), borderline mPAP (n = 15), and PH (n = 25). A therapeutic intervention trial based on RHC results was performed in nine patients. The values of tricuspid regurgitation pressure gradient (TRPG) in patients with borderline mPAP were comparable at rest but became higher after exercise compared to those with a normal mPAP (P = 0.01). Pulmonary artery wedge pressure in patients with borderline mPAP was higher than in those with normal mPAP (P < 0.0001) and comparable to those with PH. Each of the three patients was treated for pre-capillary and post-capillary disease and two for interstitial lung disease (ILD). During the mean follow-up period of 40 months, mPAP or TRPG normalized in all patients treated for pre-capillary and post-capillary disease. One patient with severe ILD developed to PH and died from it. CTD patients with borderline mPAP, the underlining pathogenesis of which is heterogeneous as PH, have distinctive hemodynamic characteristics from those with normal mPAP. Whether a specific treatment targeting the inflammatory process or local hemodynamics may alter the clinical course to PH is a topic for future research.

Elevated plasma endothelin-1 and pulmonary arterial pressure in children exposed to air pollution.

PubMed

Calderón-Garcidueñas, Lilian; Vincent, Renaud; Mora-Tiscareño, Antonieta; Franco-Lira, Maricela; Henríquez-Roldán, Carlos; Barragán-Mejía, Gerardo; Garrido-García, Luis; Camacho-Reyes, Laura; Valencia-Salazar, Gildardo; Paredes, Rogelio; Romero, Lina; Osnaya, Hector; Villarreal-Calderón, Rafael; Torres-Jardón, Ricardo; Hazucha, Milan J; Reed, William

2007-08-01

Controlled exposures of animals and humans to particulate matter (PM) or ozone air pollution cause an increase in plasma levels of endothelin-1, a potent vasoconstrictor that regulates pulmonary arterial pressure. The primary objective of this field study was to determine whether Mexico City children, who are chronically exposed to levels of PM and O(3) that exceed the United States air quality standards, have elevated plasma endothelin-1 levels and pulmonary arterial pressures. We conducted a study of 81 children, 7.9 +/- 1.3 years of age, lifelong residents of either northeast (n = 19) or southwest (n = 40) Mexico City or Polotitlán (n = 22), a control city with PM and O(3) levels below the U.S. air quality standards. Clinical histories, physical examinations, and complete blood counts were done. Plasma endothelin-1 concentrations were determined by immunoassay, and pulmonary arterial pressures were measured by Doppler echocardiography. Mexico City children had higher plasma endothelin-1 concentrations compared with controls (p < 0.001). Mean pulmonary arterial pressure was elevated in children from both northeast (p < 0.001) and southwest (p < 0.05) Mexico City compared with controls. Endothelin-1 levels in Mexico City children were positively correlated with daily outdoor hours (p = 0.012), and 7-day cumulative levels of PM air pollution < 2.5 mum in aerodynamic diameter (PM(2.5)) before endothelin-1 measurement (p = 0.03). Chronic exposure of children to PM(2.5) is associated with increased levels of circulating endothelin-1 and elevated mean pulmonary arterial pressure.

A semi-automatic framework of measuring pulmonary arterial metrics at anatomic airway locations using CT imaging

NASA Astrophysics Data System (ADS)

Jin, Dakai; Guo, Junfeng; Dougherty, Timothy M.; Iyer, Krishna S.; Hoffman, Eric A.; Saha, Punam K.

2016-03-01

Pulmonary vascular dysfunction has been implicated in smoking-related susceptibility to emphysema. With the growing interest in characterizing arterial morphology for early evaluation of the vascular role in pulmonary diseases, there is an increasing need for the standardization of a framework for arterial morphological assessment at airway segmental levels. In this paper, we present an effective and robust semi-automatic framework to segment pulmonary arteries at different anatomic airway branches and measure their cross-sectional area (CSA). The method starts with user-specified endpoints of a target arterial segment through a custom-built graphical user interface. It then automatically detect the centerline joining the endpoints, determines the local structure orientation and computes the CSA along the centerline after filtering out the adjacent pulmonary structures, such as veins or airway walls. Several new techniques are presented, including collision-impact based cost function for centerline detection, radial sample-line based CSA computation, and outlier analysis of radial distance to subtract adjacent neighboring structures in the CSA measurement. The method was applied to repeat-scan pulmonary multirow detector CT (MDCT) images from ten healthy subjects (age: 21-48 Yrs, mean: 28.5 Yrs; 7 female) at functional residual capacity (FRC). The reproducibility of computed arterial CSA from four airway segmental regions in middle and lower lobes was analyzed. The overall repeat-scan intra-class correlation (ICC) of the computed CSA from all four airway regions in ten subjects was 96% with maximum ICC found at LB10 and RB4 regions.

Acute and chronic dissection of pulmonary artery: new challenges in pulmonary arterial hypertension?

PubMed

Florczyk, Michał; Wieteska, Maria; Kurzyna, Marcin; Gościniak, Piotr; Pepke-Żaba, Joanna; Biederman, Andrzej; Torbicki, Adam

2018-01-01

Right ventricular failure is a leading cause of mortality in patients with pulmonary arterial hypertension (PAH). However, up to 25% of such patients die unexpectedly, without warning signs of hemodynamical decompensation. We previously documented that pulmonary artery (PA) dilatation significantly increases the risk of those deaths. Some of them may be due to dissection of PA resulting in cardiac tamponade. However, direct confirmation of this mechanism is difficult as most of such deaths occur outside hospitals. We present 4 patients with severe PAH and PA dilatation in whom PA dissection has been confirmed. Three patients had IPAH, one had PAH associated with congenital heart disease. All patients had mean pulmonary artery pressure (PAP) > 50 mmHg at diagnosis and dissection occurred late in the course of apparently well controlled disease (6 to 14 years). Several clinical elements were common to our patients - high systolic PAP, long lasting PH, progressive dilatation of PA to more than 50 mm with chest pain prior to dissection. However, clinical course followed three different patterns: sudden death due to cardiac tamponade, hemopericarditis caused by blood leaking from dissected aneurysm with imminent but not immediate cardiac tamponade, or chronic asymptomatic PA dissection. Indeed, two of our patients are alive and on lung transplantation waiting list for more than 2 years now. Further research is needed to suggest optimal management strategies for patients with stable PAH but significantly dilated proximal pulmonary arteries or confirmed PA dissection depending on the clinical presentation and expected outcome.

Automation process for morphometric analysis of volumetric CT data from pulmonary vasculature in rats.

PubMed

Shingrani, Rahul; Krenz, Gary; Molthen, Robert

2010-01-01

With advances in medical imaging scanners, it has become commonplace to generate large multidimensional datasets. These datasets require tools for a rapid, thorough analysis. To address this need, we have developed an automated algorithm for morphometric analysis incorporating A Visualization Workshop computational and image processing libraries for three-dimensional segmentation, vascular tree generation and structural hierarchical ordering with a two-stage numeric optimization procedure for estimating vessel diameters. We combine this new technique with our mathematical models of pulmonary vascular morphology to quantify structural and functional attributes of lung arterial trees. Our physiological studies require repeated measurements of vascular structure to determine differences in vessel biomechanical properties between animal models of pulmonary disease. Automation provides many advantages including significantly improved speed and minimized operator interaction and biasing. The results are validated by comparison with previously published rat pulmonary arterial micro-CT data analysis techniques, in which vessels were manually mapped and measured using intense operator intervention. Published by Elsevier Ireland Ltd.

MURC deficiency in smooth muscle attenuates pulmonary hypertension.

PubMed

Nakanishi, Naohiko; Ogata, Takehiro; Naito, Daisuke; Miyagawa, Kotaro; Taniguchi, Takuya; Hamaoka, Tetsuro; Maruyama, Naoki; Kasahara, Takeru; Nishi, Masahiro; Matoba, Satoaki; Ueyama, Tomomi

2016-08-22

Emerging evidence suggests that caveolin-1 (Cav1) is associated with pulmonary arterial hypertension. MURC (also called Cavin-4) is a member of the cavin family, which regulates caveolar formation and functions together with caveolins. Here, we show that hypoxia increased Murc mRNA expression in the mouse lung, and that Murc-null mice exhibited attenuation of hypoxia-induced pulmonary hypertension (PH) accompanied by reduced ROCK activity in the lung. Conditional knockout mice lacking Murc in smooth muscle also resist hypoxia-induced PH. MURC regulates the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) through Rho/ROCK signalling. Cav1 suppresses RhoA activity in PASMCs, which is reversed by MURC. MURC binds to Cav1 and inhibits the association of Cav1 with the active form of Gα13, resulting in the facilitated association of the active form of Gα13 with p115RhoGEF. These results reveal that MURC has a function in the development of PH through modulating Rho/ROCK signalling.

MURC deficiency in smooth muscle attenuates pulmonary hypertension

PubMed Central

Nakanishi, Naohiko; Ogata, Takehiro; Naito, Daisuke; Miyagawa, Kotaro; Taniguchi, Takuya; Hamaoka, Tetsuro; Maruyama, Naoki; Kasahara, Takeru; Nishi, Masahiro; Matoba, Satoaki; Ueyama, Tomomi

2016-01-01

Emerging evidence suggests that caveolin-1 (Cav1) is associated with pulmonary arterial hypertension. MURC (also called Cavin-4) is a member of the cavin family, which regulates caveolar formation and functions together with caveolins. Here, we show that hypoxia increased Murc mRNA expression in the mouse lung, and that Murc-null mice exhibited attenuation of hypoxia-induced pulmonary hypertension (PH) accompanied by reduced ROCK activity in the lung. Conditional knockout mice lacking Murc in smooth muscle also resist hypoxia-induced PH. MURC regulates the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) through Rho/ROCK signalling. Cav1 suppresses RhoA activity in PASMCs, which is reversed by MURC. MURC binds to Cav1 and inhibits the association of Cav1 with the active form of Gα13, resulting in the facilitated association of the active form of Gα13 with p115RhoGEF. These results reveal that MURC has a function in the development of PH through modulating Rho/ROCK signalling. PMID:27546070

Connective tissue disease-associated pulmonary arterial hypertension

PubMed Central

Howard, Luke S.

2015-01-01

Although rare in its idiopathic form, pulmonary arterial hypertension (PAH) is not uncommon in association with various associated medical conditions, most notably connective tissue disease (CTD). In particular, it develops in approximately 10% of patients with systemic sclerosis and so these patients are increasingly screened to enable early detection. The response of patients with systemic sclerosis to PAH-specific therapy appears to be worse than in other forms of PAH. Survival in systemic sclerosis-associated PAH is inferior to that observed in idiopathic PAH. Potential reasons for this include differences in age, the nature of the underlying pulmonary vasculopathy and the ability of the right ventricle to cope with increased afterload between patients with systemic sclerosis-associated PAH and idiopathic PAH, while coexisting cardiac and pulmonary disease is common in systemic sclerosis-associated PAH. Other forms of connective tissue-associated PAH have been less well studied, however PAH associated with systemic lupus erythematosus (SLE) has a better prognosis than systemic sclerosis-associated PAH and likely responds to immunosuppression. PMID:25705389

Analysis of volatile compounds in exhaled breath condensate in patients with severe pulmonary arterial hypertension.

PubMed

Mansoor, J K; Schelegle, Edward S; Davis, Cristina E; Walby, William F; Zhao, Weixiang; Aksenov, Alexander A; Pasamontes, Alberto; Figueroa, Jennifer; Allen, Roblee

2014-01-01

An important challenge to pulmonary arterial hypertension (PAH) diagnosis and treatment is early detection of occult pulmonary vascular pathology. Symptoms are frequently confused with other disease entities that lead to inappropriate interventions and allow for progression to advanced states of disease. There is a significant need to develop new markers for early disease detection and management of PAH. Exhaled breath condensate (EBC) samples were compared from 30 age-matched normal healthy individuals and 27 New York Heart Association functional class III and IV idiopathic pulmonary arterial hypertenion (IPAH) patients, a subgroup of PAH. Volatile organic compounds (VOC) in EBC samples were analyzed using gas chromatography/mass spectrometry (GC/MS). Individual peaks in GC profiles were identified in both groups and correlated with pulmonary hemodynamic and clinical endpoints in the IPAH group. Additionally, GC/MS data were analyzed using autoregression followed by partial least squares regression (AR/PLSR) analysis to discriminate between the IPAH and control groups. After correcting for medicaitons, there were 62 unique compounds in the control group, 32 unique compounds in the IPAH group, and 14 in-common compounds between groups. Peak-by-peak analysis of GC profiles of IPAH group EBC samples identified 6 compounds significantly correlated with pulmonary hemodynamic variables important in IPAH diagnosis. AR/PLSR analysis of GC/MS data resulted in a distinct and identifiable metabolic signature for IPAH patients. These findings indicate the utility of EBC VOC analysis to discriminate between severe IPAH and a healthy population; additionally, we identified potential novel biomarkers that correlated with IPAH pulmonary hemodynamic variables that may be important in screening for less severe forms IPAH.

Analysis of Volatile Compounds in Exhaled Breath Condensate in Patients with Severe Pulmonary Arterial Hypertension

PubMed Central

Mansoor, J. K.; Schelegle, Edward S.; Davis, Cristina E.; Walby, William F.; Zhao, Weixiang; Aksenov, Alexander A.; Pasamontes, Alberto; Figueroa, Jennifer; Allen, Roblee

2014-01-01

Background An important challenge to pulmonary arterial hypertension (PAH) diagnosis and treatment is early detection of occult pulmonary vascular pathology. Symptoms are frequently confused with other disease entities that lead to inappropriate interventions and allow for progression to advanced states of disease. There is a significant need to develop new markers for early disease detection and management of PAH. Methodolgy and Findings Exhaled breath condensate (EBC) samples were compared from 30 age-matched normal healthy individuals and 27 New York Heart Association functional class III and IV idiopathic pulmonary arterial hypertenion (IPAH) patients, a subgroup of PAH. Volatile organic compounds (VOC) in EBC samples were analyzed using gas chromatography/mass spectrometry (GC/MS). Individual peaks in GC profiles were identified in both groups and correlated with pulmonary hemodynamic and clinical endpoints in the IPAH group. Additionally, GC/MS data were analyzed using autoregression followed by partial least squares regression (AR/PLSR) analysis to discriminate between the IPAH and control groups. After correcting for medicaitons, there were 62 unique compounds in the control group, 32 unique compounds in the IPAH group, and 14 in-common compounds between groups. Peak-by-peak analysis of GC profiles of IPAH group EBC samples identified 6 compounds significantly correlated with pulmonary hemodynamic variables important in IPAH diagnosis. AR/PLSR analysis of GC/MS data resulted in a distinct and identifiable metabolic signature for IPAH patients. Conclusions These findings indicate the utility of EBC VOC analysis to discriminate between severe IPAH and a healthy population; additionally, we identified potential novel biomarkers that correlated with IPAH pulmonary hemodynamic variables that may be important in screening for less severe forms IPAH. PMID:24748102

Pulmonary hypertension registry of Kerala, India (PRO-KERALA) - Clinical characteristics and practice patterns.

PubMed

Harikrishnan, S; Sanjay, G; Ashishkumar, M; Menon, Jaideep; Rajesh, Gopalan Nair; Kumar, Raman Krishna; George Koshy, A; Attacheril, Thankachan V; George, Raju; Punnoose, Eapen; Ashraf, S M; Arun, S R; Cholakkal, Mohammed; Jeemon, Panniyammakal

2018-08-15

Epidemiological data on pulmonary hypertension (PH) are scarce from developing countries including India. We established a multi-center registry of PH, the PRO-KERALA registry, in Kerala, India. Fifty hospitals enrolled consecutive adult (>18 years) patients for one year. Echocardiographic criteria (right ventricular systolic pressure - RVSP > 50 mmHg) or invasively obtained mean pulmonary artery pressure > 25 mmHg was the criteria for entry. There were 2003 patients (52% Women, mean age 56 ± 16.1 years) enrolled. The mean RVSP was 68.2 (SD = 17.9) mmHg. Majority of the study participants (59%) belonged to group 2 of the WHO Nice Classification 2013 (PH secondary to left heart disease). One-fifth (21.2%) belonged to group 1, while 13.3%, 3.8% and 2.4% of the study population belonged to groups 3, 4 and 5 respectively. More than a quarter (27%) reported PH due to left heart disease with valvular disease etiology; while 20.7% had coronary artery disease. The other common etiological factors were chronic obstructive pulmonary disease (10.6%), congenital heart disease (14.6%), idiopathic pulmonary hypertension (5.8%), and chronic thromboembolic pulmonary hypertension (3.8%). Only one of two patients with pulmonary artery hypertension was receiving PH specific therapies. The use of combination therapy was negligible and PH-specific therapies were prescribed off-label to a small proportion of patients too. PRO-KERALA is the first PH registry from South Asia and the second largest globally. Left heart diseases attribute to three fifths of patients with PH. Utilization rates of PH specific drug therapies are remarkably lower than the Western population. Copyright © 2018 Elsevier B.V. All rights reserved.

Sildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp: a randomized, double-blind, placebo-controlled crossover trial.

PubMed

Ghofrani, Hossein A; Reichenberger, Frank; Kohstall, Markus G; Mrosek, Eike H; Seeger, Timon; Olschewski, Horst; Seeger, Werner; Grimminger, Friedrich

2004-08-03

Alveolar hypoxia causes pulmonary hypertension and enhanced right ventricular afterload, which may impair exercise tolerance. The phosphodiesterase-5 inhibitor sildenafil has been reported to cause pulmonary vasodilatation. To investigate the effects of sildenafil on exercise capacity under conditions of hypoxic pulmonary hypertension. Randomized, double-blind, placebo-controlled crossover study. University Hospital Giessen, Giessen, Germany, and the base camp on Mount Everest. 14 healthy mountaineers and trekkers. Systolic pulmonary artery pressure, cardiac output, and peripheral arterial oxygen saturation at rest and during assessment of maximum exercise capacity on cycle ergometry 1) while breathing a hypoxic gas mixture with 10% fraction of inspired oxygen at low altitude (Giessen) and 2) at high altitude (the Mount Everest base camp). Oral sildenafil, 50 mg, or placebo. At low altitude, acute hypoxia reduced arterial oxygen saturation to 72.0% (95% CI, 66.5% to 77.5%) at rest and 60.8% (CI, 56.0% to 64.5%) at maximum exercise capacity. Systolic pulmonary artery pressure increased from 30.5 mm Hg (CI, 26.0 to 35.0 mm Hg) at rest to 42.9 mm Hg (CI, 35.6 to 53.5 mm Hg) during exercise in participants taking placebo. Sildenafil, 50 mg, significantly increased arterial oxygen saturation during exercise (P = 0.005) and reduced systolic pulmonary artery pressure at rest (P < 0.001) and during exercise (P = 0.031). Of note, sildenafil increased maximum workload (172.5 W [CI, 147.5 to 200.0 W]) vs. 130.6 W [CI, 108.8 to 150.0 W]); P < 0.001) and maximum cardiac output (P < 0.001) compared with placebo. At high altitude, sildenafil had no effect on arterial oxygen saturation at rest and during exercise compared with placebo. However, sildenafil reduced systolic pulmonary artery pressure at rest (P = 0.003) and during exercise (P = 0.021) and increased maximum workload (P = 0.002) and cardiac output (P = 0.015). At high altitude, sildenafil exacerbated existing headache in 2 participants. The study did not examine the effects of sildenafil on normoxic exercise tolerance. Sildenafil reduces hypoxic pulmonary hypertension at rest and during exercise while maintaining gas exchange and systemic blood pressure. To the authors' knowledge, sildenafil is the first drug shown to increase exercise capacity during severe hypoxia both at sea level and at high altitude.

Resting arterial hypoxaemia in subjects with chronic heart failure, pulmonary hypertension and patent foramen ovale.

PubMed

Lovering, Andrew T; Lozo, Mislav; Barak, Otto; Davis, James T; Lojpur, Mihajlo; Lozo, Petar; Čaljkušić, Krešimir; Dujić, Željko

2016-05-01

What is the central question of this study? Does a patent foramen ovale contribute to resting arterial hypoxaemia, defined as arterial oxygen saturation <95%, in subjects with chronic heart failure with or without pulmonary arterial hypertension? What is the main finding and its importance? The presence of a patent foramen ovale contributed to resting arterial hypoxaemia only in subjects with chronic heart failure with pulmonary arterial hypertension. These data suggest that the presence of a patent foramen ovale should be considered in chronic heart failure patients with arterial hypoxaemia and pulmonary hypertension. The roles of intrapulmonary and intracardiac shunt in contributing to arterial hypoxaemia at rest in subjects with chronic heart failure (CHF) have not been well investigated. We hypothesized that blood flow through intrapulmonary arteriovenous anastomoses (Q̇ IPAVA ) and/or patent foramen ovale (Q̇ PFO ) could potentially contribute to arterial hypoxaemia and, with pulmonary hypertension (PH) secondary to CHF, this contribution may be exacerbated. Fifty-six subjects with CHF (New York Heart Association Classes I-III), with (+) or without (-) PH [defined as peak tricuspid regurgitation velocity ≥2.9 m s(-1) (CHF PH+, n = 32) and peak tricuspid regurgitation velocity ≤2.8 m s(-1) (CHF PH-, n = 24)], underwent arterial blood gas analysis and transthoracic saline contrast echocardiography concomitant with transcranial Doppler to detect Q̇ IPAVA and Q̇ PFO . Seventeen of 56 subjects with CHF (30%) had Q̇ PFO , but only four of 56 subjects with CHF had Q̇ IPAVA (7%), both similar to age- and sex-matched control subjects. Mean arterial oxygen saturation (SaO2) was lower in subjects with Q̇ PFO . Only CHF PH+ subjects with Q̇ PFO had arterial hypoxaemia (mean SaO2 <95%). Bubble scores assessed using transthoracic saline contrast echocardiography were correlated with microembolic signals detected with transcranial Doppler in subjects with Q̇ PFO . Significant Q̇ IPAVA was not present in either CHF PH+ or PH- subjects, suggesting that Q̇ IPAVA is not dependent on increased pulmonary pressure and does not contribute significantly to arterial hypoxaemia in older subjects with CHF. Given that SaO2 was lower in all subjects with CHF who had Q̇ PFO compared with those without Q̇ PFO , a patent foramen ovale should be considered when determining potential causes of arterial hypoxaemia, because Q̇ PFO was present in 30% of these subjects. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Perinatal hypoxia increases susceptibility to high-altitude polycythemia and attendant pulmonary vascular dysfunction

PubMed Central

Gonzales, Marcelino; Rodriguez, Armando; Bellido, Diva; Salmon, Carlos Salinas; Ladenburger, Anne; Reardon, Lindsay; Vargas, Enrique; Moore, Lorna G.

2015-01-01

Perinatal exposures exert a profound influence on physiological function, including developmental processes vital for efficient pulmonary gas transfer throughout the lifespan. We extend the concept of developmental programming to chronic mountain sickness (CMS), a debilitating syndrome marked by polycythemia, ventilatory impairment, and pulmonary hypertension that affects ∼10% of male high-altitude residents. We hypothesized that adverse perinatal oxygenation caused abnormalities of ventilatory and/or pulmonary vascular function that increased susceptibility to CMS in adulthood. Subjects were 67 male high-altitude (3,600–4,100 m) residents aged 18–25 yr with excessive erythrocytosis (EE, Hb concentration ≥18.3 g/dl), a preclinical form of CMS, and 66 controls identified from a community-based survey (n = 981). EE subjects not only had higher Hb concentrations and erythrocyte counts, but also lower alveolar ventilation, impaired pulmonary diffusion capacity, higher systolic pulmonary artery pressure, lower pulmonary artery acceleration time, and more frequent right ventricular hypertrophy, than controls. Compared with controls, EE subjects were more often born to mothers experiencing hypertensive complications of pregnancy and hypoxia during the perinatal period, with each increasing the risk of developing EE (odds ratio = 5.25, P = 0.05 and odds ratio = 6.44, P = 0.04, respectively) after other factors known to influence EE status were taken into account. Adverse perinatal oxygenation is associated with increased susceptibility to EE accompanied by modest abnormalities of the pulmonary circulation that are independent of increased blood viscosity. The association between perinatal hypoxia and EE may be due to disrupted alveolarization and microvascular development, leading to impaired gas exchange and/or pulmonary hypertension. PMID:26092986

Perinatal hypoxia increases susceptibility to high-altitude polycythemia and attendant pulmonary vascular dysfunction.

PubMed

Julian, Colleen Glyde; Gonzales, Marcelino; Rodriguez, Armando; Bellido, Diva; Salmon, Carlos Salinas; Ladenburger, Anne; Reardon, Lindsay; Vargas, Enrique; Moore, Lorna G

2015-08-15

Perinatal exposures exert a profound influence on physiological function, including developmental processes vital for efficient pulmonary gas transfer throughout the lifespan. We extend the concept of developmental programming to chronic mountain sickness (CMS), a debilitating syndrome marked by polycythemia, ventilatory impairment, and pulmonary hypertension that affects ∼10% of male high-altitude residents. We hypothesized that adverse perinatal oxygenation caused abnormalities of ventilatory and/or pulmonary vascular function that increased susceptibility to CMS in adulthood. Subjects were 67 male high-altitude (3,600-4,100 m) residents aged 18-25 yr with excessive erythrocytosis (EE, Hb concentration ≥18.3 g/dl), a preclinical form of CMS, and 66 controls identified from a community-based survey (n = 981). EE subjects not only had higher Hb concentrations and erythrocyte counts, but also lower alveolar ventilation, impaired pulmonary diffusion capacity, higher systolic pulmonary artery pressure, lower pulmonary artery acceleration time, and more frequent right ventricular hypertrophy, than controls. Compared with controls, EE subjects were more often born to mothers experiencing hypertensive complications of pregnancy and hypoxia during the perinatal period, with each increasing the risk of developing EE (odds ratio = 5.25, P = 0.05 and odds ratio = 6.44, P = 0.04, respectively) after other factors known to influence EE status were taken into account. Adverse perinatal oxygenation is associated with increased susceptibility to EE accompanied by modest abnormalities of the pulmonary circulation that are independent of increased blood viscosity. The association between perinatal hypoxia and EE may be due to disrupted alveolarization and microvascular development, leading to impaired gas exchange and/or pulmonary hypertension. Copyright © 2015 the American Physiological Society.

Patient-Specific Simulations of Reactivity in Models of the Pulmonary Vasculature: A 3-D Numerical Study with Fluid-Structure Interaction

NASA Astrophysics Data System (ADS)

Hunter, Kendall; Zhang, Yanhang; Lanning, Craig

2005-11-01

Insight into the progression of pulmonary hypertension may be obtained from thorough study of vascular flow during reactivity testing, an invasive diagnostic procedure which can dramatically alter vascular hemodynamics. Diagnostic imaging methods, however, are limited in their ability to provide extensive data. Here we present detailed flow and wall deformation results from simulations of pulmonary arteries undergoing this procedure. Patient-specific 3-D geometric reconstructions of the first four branches of the pulmonary vasculature were obtained clinically and meshed for use with computational software. Transient simulations in normal and reactive states were obtained from four such models were completed with patient-specific velocity inlet conditions and flow impedance exit conditions. A microstructurally based orthotropic hyperelastic model that simulates pulmonary artery mechanics under normotensive and hypoxic hypertensive conditions treated wall constitutive changes due to pressure reactivity and arterial remodeling. Pressure gradients, velocity fields, arterial deformation, and complete topography of shear stress were obtained. These models provide richer detail of hemodynamics than can be obtained from current imaging techniques, and should allow maximum characterization of vascular function in the clinical situation.

A pilot study of the effect of spironolactone therapy on exercise capacity and endothelial dysfunction in pulmonary arterial hypertension: study protocol for a randomized controlled trial.

PubMed

Elinoff, Jason M; Rame, J Eduardo; Forfia, Paul R; Hall, Mary K; Sun, Junfeng; Gharib, Ahmed M; Abd-Elmoniem, Khaled; Graninger, Grace; Harper, Bonnie; Danner, Robert L; Solomon, Michael A

2013-04-02

Pulmonary arterial hypertension is a rare disorder associated with poor survival. Endothelial dysfunction plays a central role in the pathogenesis and progression of pulmonary arterial hypertension. Inflammation appears to drive this dysfunctional endothelial phenotype, propagating cycles of injury and repair in genetically susceptible patients with idiopathic and disease-associated pulmonary arterial hypertension. Therapy targeting pulmonary vascular inflammation to interrupt cycles of injury and repair and thereby delay or prevent right ventricular failure and death has not been tested. Spironolactone, a mineralocorticoid and androgen receptor antagonist, has been shown to improve endothelial function and reduce inflammation. Current management of patients with pulmonary arterial hypertension and symptoms of right heart failure includes use of mineralocorticoid receptor antagonists for their diuretic and natriuretic effects. We hypothesize that initiating spironolactone therapy at an earlier stage of disease in patients with pulmonary arterial hypertension could provide additional benefits through anti-inflammatory effects and improvements in pulmonary vascular function. Seventy patients with pulmonary arterial hypertension without clinical evidence of right ventricular failure will be enrolled in a randomized, double-blinded, placebo-controlled trial to investigate the effect of early treatment with spironolactone on exercise capacity, clinical worsening and vascular inflammation in vivo. Our primary endpoint is change in placebo-corrected 6-minute walk distance at 24 weeks and the incidence of clinical worsening in the spironolactone group compared to placebo. At a two-sided alpha level of 0.05, we will have at least 84% power to detect an effect size (group mean difference divided by standard deviation) of 0.9 for the difference in the change of 6-minute walk distance from baseline between the two groups. Secondary endpoints include the effect of spironolactone on the change in placebo-corrected maximal oxygen consumption; plasma markers of vascular inflammation and peripheral blood mononuclear cell gene expression profiles; sympathetic nervous system activation, renin-angiotensin-aldosterone system activation and sex hormone metabolism; and right ventricular structure and function using echocardiography and novel high-resolution magnetic resonance imaging-based techniques. Safety and tolerability of spironolactone will be assessed with periodic monitoring for hyperkalemia and renal insufficiency as well as the incidence of drug discontinuation for untoward effects. ClinicalTrials.gov: NCT01712620.

A pilot study of the effect of spironolactone therapy on exercise capacity and endothelial dysfunction in pulmonary arterial hypertension: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Pulmonary arterial hypertension is a rare disorder associated with poor survival. Endothelial dysfunction plays a central role in the pathogenesis and progression of pulmonary arterial hypertension. Inflammation appears to drive this dysfunctional endothelial phenotype, propagating cycles of injury and repair in genetically susceptible patients with idiopathic and disease-associated pulmonary arterial hypertension. Therapy targeting pulmonary vascular inflammation to interrupt cycles of injury and repair and thereby delay or prevent right ventricular failure and death has not been tested. Spironolactone, a mineralocorticoid and androgen receptor antagonist, has been shown to improve endothelial function and reduce inflammation. Current management of patients with pulmonary arterial hypertension and symptoms of right heart failure includes use of mineralocorticoid receptor antagonists for their diuretic and natriuretic effects. We hypothesize that initiating spironolactone therapy at an earlier stage of disease in patients with pulmonary arterial hypertension could provide additional benefits through anti-inflammatory effects and improvements in pulmonary vascular function. Methods/Design Seventy patients with pulmonary arterial hypertension without clinical evidence of right ventricular failure will be enrolled in a randomized, double-blinded, placebo-controlled trial to investigate the effect of early treatment with spironolactone on exercise capacity, clinical worsening and vascular inflammation in vivo. Our primary endpoint is change in placebo-corrected 6-minute walk distance at 24 weeks and the incidence of clinical worsening in the spironolactone group compared to placebo. At a two-sided alpha level of 0.05, we will have at least 84% power to detect an effect size (group mean difference divided by standard deviation) of 0.9 for the difference in the change of 6-minute walk distance from baseline between the two groups. Secondary endpoints include the effect of spironolactone on the change in placebo-corrected maximal oxygen consumption; plasma markers of vascular inflammation and peripheral blood mononuclear cell gene expression profiles; sympathetic nervous system activation, renin-angiotensin-aldosterone system activation and sex hormone metabolism; and right ventricular structure and function using echocardiography and novel high-resolution magnetic resonance imaging-based techniques. Safety and tolerability of spironolactone will be assessed with periodic monitoring for hyperkalemia and renal insufficiency as well as the incidence of drug discontinuation for untoward effects. Trial registration ClinicalTrials.gov: NCT01712620 PMID:23547564

Mechanisms of oxygen sensing: a key to therapy of pulmonary hypertension and patent ductus arteriosus

PubMed Central

Weir, E K; Obreztchikova, M; Vargese, A; Cabrera, J A; Peterson, D A; Hong, Z

2008-01-01

Specialized tissues that sense acute changes in the local oxygen tension include type 1 cells of the carotid body, neuroepithelial bodies in the lungs, and smooth muscle cells of the resistance pulmonary arteries and the ductus arteriosus (DA). Hypoxia inhibits outward potassium current in carotid body type 1 cells, leading to depolarization and calcium entry through L-type calcium channels. Increased intracellular calcium concentration ([Ca++]i) leads to exocytosis of neurotransmitters, thus stimulating the carotid sinus nerve and respiration. The same K+ channel inhibition occurs with hypoxia in pulmonary artery smooth muscle cells (PASMCs), causing contraction and providing part of the mechanism of hypoxic pulmonary vasoconstriction (HPV). In the SMCs of the DA, the mechanism works in reverse. It is the shift from hypoxia to normoxia that inhibits K+ channels and causes normoxic ductal contraction. In both PA and DA, the contraction is augmented by release of Ca++ from the sarcoplasmic reticulum, entry of Ca++ through store-operated channels (SOC) and by Ca++ sensitization. The same three ‘executive' mechanisms are partly responsible for idiopathic pulmonary arterial hypertension (IPAH). While vasoconstrictor mediators constrict both PA and DA and vasodilators dilate both vessels, only redox changes mimic oxygen by having directly opposite effects on the K+ channels, membrane potential, [Ca++]i and tone in the PA and DA. There are several different hypotheses as to how redox might alter tone, which remain to be resolved. However, understanding the mechanism will facilitate drug development for pulmonary hypertension and patent DA. PMID:18641675

15-LO/15-HETE mediated vascular adventitia fibrosis via p38 MAPK-dependent TGF-β.

PubMed

Zhang, Li; Li, Yumei; Chen, Minggang; Su, Xiaojie; Yi, Dan; Lu, Ping; Zhu, Daling

2014-02-01

15-Lipoxygenase/15-hydroxyeicosatetraenoic acid (15-LO/15-HETE) is known to modulate pulmonary vascular medial hypertrophy and intimal endothelial cells migration and angiogenesis after hypoxia. However, it is unclear whether 15-HETE affects the adventitia of the pulmonary arterial wall. We performed immunohistochemistry, adventitia fibrosis, pulmonary artery fibroblasts phenotype and extracellular matrix (ECM) deposition to determine the role of 15-HETE in hypoxia-induced pulmonary vascular adventitia remodeling. Our studies showed that O2 deprivation induced adventitia hypertrophy of pulmonary arteries with ECM accumulation in both humans with pulmonary arterial hypertension and hypoxic rats. Hypoxia induced 15-LO expression in adventitia. With the inhibitor, NDGA depressed the hypoxia induced ECM deposition and 15-LO production in hypoxic rats. Hypoxia up-regulated the expression of α-SMA, type-Ia collagen and fibronectin in cultured fibroblasts, which seemed to be due to the increased 15-LO/15-HETE. Exogenous 15-HETE mediated the ECM and phenotypic alterations of the fibroblasts as well. The 15-LO/15-HETE induced adventitia fibrosis and fibroblasts phenotypic alterations depended on signaling of the transforming growth factor-β1 (TGF-β1)/Smad2/3 pathway. P38 mitogen-activated protein kinase (p38 MAPKs) was likely to mediate 15-LO induced TGF-β1 and Smad2/3 activation after hypoxia. The results suggest that adventitia fibrosis is an important event in the hypoxia induced pulmonary arterial remodeling, which relies on 15-LO/15-HETE induced p38 MAPK-dependent TGF-β1/Smad2/3 intracellular signaling systems. © 2013 Wiley Periodicals, Inc.

Presence of reduced regional left ventricular function even in the absence of left ventricular wall scar tissue in the long term after repair of an anomalous left coronary artery from the pulmonary artery.

PubMed

Nordmeyer, Sarah; Schmitt, Boris; Nasseri, Boris; Alexi-Meskishvili, Vladimir; Kuehne, Titus; Berger, Felix; Nordmeyer, Johannes

2018-02-01

We sought to assess left ventricular regional function in patients with and without left ventricular wall scar tissue in the long term after repair of an anomalous origin of the left coronary artery from the pulmonary artery. A total of 20 patients aged 12.8±7.4 years were assessed 10 (0.5-17) years after the repair of an anomalous origin of the left coronary artery from the pulmonary artery; of them, 10 (50%) patients showed left ventricular wall scar tissue on current cardiac MRI. Left ventricular regional function was assessed by two-dimensional speckle-tracking echocardiography in 10 patients with scar tissue and 10 patients without scar tissue and in 10 age-matched controls. In patients with scar tissue, MRI-derived left ventricular ejection fraction was significantly reduced compared with that in patients without scar tissue (51 versus 61%, p<0.05), and echocardiography-derived longitudinal strain was significantly reduced in five of six left ventricular areas compared with that in healthy controls (average relative reduction, 46%; p<0.05). In patients without scar tissue, longitudinal strain was significantly reduced in two of six left ventricular areas (average relative reduction, 23%; p<0.05) and circumferential strain was reduced in one of six left ventricular areas (relative reduction, 56%; p<0.05) compared with that in healthy controls. Regional left ventricular function is reduced even in patients without left ventricular wall scar tissue late after successful repair of an anomalous origin of the left coronary artery from the pulmonary artery. This highlights the need for meticulous lifelong follow-up in all patients with a repaired anomalous origin of the left coronary artery from the pulmonary artery.

[Analysis of factors related to pulmonary hypertensive crisis in patients with idiopathic pulmonary arterial hypertension].

PubMed

Zhang, Chen; Li, Qiangqiang; Zhu, Yan; Gu, Hong

2014-06-10

To explore the risk and protective factors for pulmonary hypertensive crisis (PHC) in patients with idiopathic pulmonary arterial hypertension (IPAH). A retrospective study was performed for 65 patients with a diagnosis of IPAH between January 2010 and December 2013. According to clinical manifestations, they were divided into two groups of susceptibility and non-susceptibility to PHC. Clinical and hemodynamic parameters were analyzed in univariate and multivariate manners. Among them, there were 32 males and 33 females with a mean age of (14.4 ± 12.3) (10/12-47.3) years. Twenty-three patients had typical manifestations of PHC and 18 of them were induced by exercises.Univariate analysis revealed that the proportion of patients with World Health Organization (WHO) functional class III-IV in PHC-susceptible group was significantly higher than PHC-nonsusceptible group (60.9% vs 23.8%, P = 0.003) while the percentage of patent foramen ovale in PHC-susceptible group was significantly lower than PHC-nonsusceptible group (8.7% vs 45.2%, P = 0.003).In patients with WHO functional classI-II, hemodynamic variables including the decline of pulmonary arterial pressure and positive rate in vasoreactivity testing in PHC-susceptible group were significantly higher than PHC-nonsusceptible group.In patients with WHO functional class III-IV, baseline pulmonary arterial pressure and mean right atrial pressure in PHC-susceptible group were significantly higher than those in PHC-nonsusceptible group. Multivariate Logistic regression analysis revealed that, for those with WHO functional class III-IV (OR = 23.45, 95%CI: 2.85-193.09) and the decline of systolic pulmonary arterial pressure in vasoreactivity testing (OR = 1.12, 95%CI: 1.04-1.22) were independent risk factors for PHC in IPAH patients while patent foramen ovale (OR = 0.01, 95%CI: 0.00-0.52) was a protective factor. PHC in IPAH patients is correlated with WHO functional class, pulmonary vascular reactivity, baseline pulmonary arterial pressure and patent foramen ovale. And exercise is the most common stimulus to PHC.

Isolated Anomalous Origin of Left Pulmonary Artery From the Descending Aorta: An Embryologic Ambiguity.

PubMed

Gnanappa, Ganesh Kumar; Laohachai, Karina; Orr, Yishay; Ayer, Julian

2016-11-01

Anomalous origin of a branch pulmonary artery from the aorta is a rare malformation, accounting for 0.12% of all congenital heart defects. Anomalous origin of the left pulmonary artery from the aorta (ALPA) constitutes a small proportion of these cases. ALPA has been reported to arise from the ascending aorta with various embryologic postulates. We report a case of isolated ALPA arising from the descending aorta in association with a patent ductus arteriosus, to emphasize its embryologic ambiguity. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Endothelial cell-dependent relaxation and contraction induced by histamine in the isolated guinea-pig pulmonary artery.

PubMed

Satoh, H; Inui, J

1984-01-27

Histamine (10(-8)-10(-6) M) relaxed in a concentration-dependent manner the guinea-pig pulmonary artery which had been contracted by noradrenaline (5 X 10(-7) M). After the removal of endothelial cells (ETCs) histamine at the same concentrations did not cause relaxation but induced additional contraction. Both responses to histamine were antagonized by chlorpheniramine (3 X 10(-7) M). These results suggest that in the pulmonary artery histamine simultaneously stimulates H1-receptors located on both ETCs and smooth muscle cells. This results in two opposite effects, relaxation mediated by ETCs, and contraction.

Agmatine Modulation of Noradrenergic Neurotransmission in Isolated Rat Blood Vessels.

PubMed

Török, Jozef; Zemančíková, Anna

2016-06-30

Agmatine, a vasoactive metabolite of L-arginine, is widely distributed in mammalian tissues including blood vessels. Agmatine binding to imidazoline and α₂-adrenoceptors induces a variety of physiological and pharmacological effects. We investigated the effect of agmatine on contractile responses of the rat pulmonary artery and portal vein induced by electrical stimulation of perivascular nerves and by exogenous adrenergic substances. Experiments were performed on isolated segments of rat main pulmonary artery and its extralobular branches, and portal vein suspended in organ bath containing modified Krebs bicarbonate solution and connected to a force-displacement transducer for isometric tension recording. Electrical field stimulation (EFS) produced tetrodotoxin-sensitive contractile responses of pulmonary artery and portal vein. Besides the well known vasorelaxant actions, we found that agmatine also produced a concentration-dependent inhibition of neurogenic contractions induced by EFS in pulmonary arteries; however, the agmatine treatment did not influence the responses to exogenous noradrenaline. The inhibitory effect on EFS-induced contractions was not abolished by the α₂-adrenoceptor antagonist rauwolscine. In portal vein, in contrast, agmatine increased spontaneous mechanical contractions and enhanced the contractions induced by EFS. The results suggest that agmatine can significantly influence vascular function of pulmonary arteries and portal veins by modulating sympathetically mediated vascular contractions by pre- and postsynaptic mechanisms.

Impact of sildenafil on survival of patients with idiopathic pulmonary arterial hypertension.

PubMed

Zeng, Wei-Jie; Sun, Yun-Juan; Gu, Qing; Xiong, Chang-Ming; Li, Jian-Jun; He, Jian-Guo

2012-09-01

It has been reported that short-term sildenafil therapy is safe and effective for patients with pulmonary arterial hypertension. However, data regarding the impact of sildenafil on the survival of patients with idiopathic pulmonary arterial hypertension remain limited. The study was conducted on 77 patients with newly diagnosed idiopathic pulmonary arterial hypertension at Fu Wai Hospital between September 2005 and September 2009. Patients were divided into 2 groups: the sildenafil group and the conventional group. Nine patients treated with sildenafil were re-evaluated by right heart catheterization after 3 months. Our data demonstrated that the 6-minute walk distance, World Health Organization functional class, mixed venous oxygen saturation, and hemodynamics significantly improved after 3 months of sildenafil therapy (P < .05). The baseline characteristics of the sildenafil group were similar to those of the conventional group. The 1-, 2-, and 3-year survival rates in the sildenafil group were 88%, 72%, and 68% compared with 61%, 36%, and 27% in the conventional group (P < .001). The absence of sildenafil therapy, lower body mass index, and lower mixed venous oxygen saturation were found to be independent predictors of mortality. In conclusion, sildenafil therapy was found to be associated with improved survival in patients with idiopathic pulmonary arterial hypertension.

Pulmonary vascular remodelling in a high-altitude Aymara Indian

NASA Astrophysics Data System (ADS)

Heath, Donald; Williams, David

1991-12-01

A histological study of the pulmonary vasculature in a young male high-altitude Aymara Indian revealed four aspects of interest. There was muscularization of the terminal portion of the pulmonary arterial tree to involve pulmonary arterioles as small as 15 μm in diameter, thus forming a basis for the slightly increased pulmonary vascular resistance of native highlanders. Intimal longitudinal muscle was found in pulmonary arteries and arterioles and thought to be due to chronic alveolar hypoxia. Inner muscular tubes similar to those found in chronic obstructive lung disease were present. Pulmonary veins and venules also showed intimal muscularization suggesting that alveolar hypoxia affects vascular smooth muscle cells per se irrespective of their situation. The nature of the remodelling in a pulmonary blood vessel depends on a combination of hypoxia and haemodynamics.

Perfusion defects in pulmonary perfusion iodine maps: causes and semiology.

PubMed

Bustos Fiore, A; González Vázquez, M; Trinidad López, C; Mera Fernández, D; Costas Álvarez, M

2017-12-14

to describe the usefulness of dual-energy CT for obtaining pulmonary perfusion maps to provide morphological and functional information in patients with pulmonary embolisms. To review the semiology of perfusion defects due to pulmonary embolism so they can be differentiated from perfusion defects due to other causes: alterations outside the range used in the iodine map caused by other diseases of the lung parenchyma or artifacts. CT angiography of the pulmonary arteries is the technique of choice for the diagnosis of pulmonary embolisms. New dual-energy CT scanners are useful for detecting perfusion defects secondary to complete or partial obstruction of pulmonary arteries and is most useful for detecting pulmonary embolisms in subsegmental branches. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Isolated Major Aortopulmonary Collateral as the Sole Pulmonary Blood Supply to an Entire Lung Segment.

PubMed

Kim, Hannah S; Grady, R Mark; Shahanavaz, Shabana

2017-01-01

Congenital systemic-to-pulmonary collateral arteries or major aortopulmonary collaterals are associated with cyanotic congenital heart disease with decreased pulmonary blood flow. Though it is usually associated with congenital heart diseases, there is an increased incidence of isolated acquired aortopulmonary collaterals in premature infants with chronic lung disease. Interestingly, isolated congenital aortopulmonary collaterals can occur without any lung disease, which may cause congestive heart failure and require closure. We present a neonate with an echocardiogram that showed only left-sided heart dilation. Further workup with a CT angiogram demonstrated an anomalous systemic artery from the descending thoracic aorta supplying the left lower lobe. He eventually developed heart failure symptoms and was taken to the catheterization laboratory for closure of the collateral. However, with the collateral being the only source of blood flow to the entire left lower lobe, he required surgical unifocalization. Isolated aortopulmonary collaterals without any other congenital heart disease or lung disease are rare. Our patient is the first reported case to have an isolated aortopulmonary collateral being the sole pulmonary blood supply to an entire lung segment. Due to its rarity, there is still much to learn about the origin and development of these collaterals that possibly developed prenatally.

Contrast Media Delivery in the Assessment of Anomalous Left Coronary Artery From the Pulmonary Artery.

PubMed

Saade, Charbel; Al-Hamra, Salam; Al-Mohiy, Hussain; El-Merhi, Fadi

2016-05-01

A patient with a history of mitral valve prolapse and regurgitation that was corrected with a mitral ring repair 15 years earlier received a diagnosis of anomalous left coronary artery arising from the pulmonary artery and underwent repair. Coronary computed tomography angiography (CTA) was employed to image the patient before surgical intervention. Synchronizing contrast media administration to opacify the right coronary artery in the arterial phase and the left coronary artery in the venous phase required a test-bolus approach. Matching compromised cardiovascular dynamics with patient-specific contrast media administration protocols was improved considerably with the use of a test-bolus technique during electrocardiography-gated coronary CTA.

Plasma proteome analysis in patients with pulmonary arterial hypertension: an observational cohort study.

PubMed

Rhodes, Christopher J; Wharton, John; Ghataorhe, Pavandeep; Watson, Geoffrey; Girerd, Barbara; Howard, Luke S; Gibbs, J Simon R; Condliffe, Robin; Elliot, Charles A; Kiely, David G; Simonneau, Gerald; Montani, David; Sitbon, Olivier; Gall, Henning; Schermuly, Ralph T; Ghofrani, H Ardeschir; Lawrie, Allan; Humbert, Marc; Wilkins, Martin R

2017-09-01

Idiopathic and heritable pulmonary arterial hypertension form a rare but molecularly heterogeneous disease group. We aimed to measure and validate differences in plasma concentrations of proteins that are associated with survival in patients with idiopathic or heritable pulmonary arterial hypertension to improve risk stratification. In this observational cohort study, we enrolled patients with idiopathic or heritable pulmonary arterial hypertension from London (UK; cohorts 1 and 2), Giessen (Germany; cohort 3), and Paris (France; cohort 4). Blood samples were collected at routine clinical appointment visits, clinical data were collected within 30 days of blood sampling, and biochemical data were collected within 7 days of blood sampling. We used an aptamer-based assay of 1129 plasma proteins, and patient clinical details were concealed to the technicians. We identified a panel of prognostic proteins, confirmed with alternative targeted assays, which we evaluated against the established prognostic risk equation for pulmonary arterial hypertension derived from the REVEAL registry. All-cause mortality was the primary endpoint. 20 proteins differentiated survivors and non-survivors in 143 consecutive patients with idiopathic or heritable pulmonary arterial hypertension with 2 years' follow-up (cohort 1) and in a further 75 patients with 2·5 years' follow-up (cohort 2). Nine proteins were both prognostic independent of plasma NT-proBNP concentrations and confirmed by targeted assays. The functions of these proteins relate to myocardial stress, inflammation, pulmonary vascular cellular dysfunction and structural dysregulation, iron status, and coagulation. A cutoff-based score using the panel of nine proteins provided prognostic information independent of the REVEAL equation, improving the C statistic from area under the curve 0·83 (for REVEAL risk score, 95% CI 0·77-0·89; p<0·0001) to 0·91 (for panel and REVEAL 0·87-0·96; p<0·0001) and improving reclassification indices without detriment to calibration. Poor survival was preceded by an adverse change in panel score in paired samples from 43 incident patients with pulmonary arterial hypertension in cohort 3 (p=0·0133). The protein panel was validated in 93 patients with idiopathic or heritable pulmonary arterial hypertension in cohort 4, with 4·4 years' follow-up and improved risk estimates, providing complementary information to the clinical risk equation. A combination of nine circulating proteins identifies patients with pulmonary arterial hypertension with a high risk of mortality, independent of existing clinical assessments, and might have a use in clinical management and the evaluation of new therapies. National Institute for Health Research, Wellcome Trust, British Heart Foundation, Assistance Publique-Hôpitaux de Paris, Inserm, Université Paris-Sud, and Agence Nationale de la Recherche. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licence. Published by Elsevier Ltd.. All rights reserved.

Benefits from the correction of vitamin D deficiency in patients with pulmonary hypertension.

PubMed

Mirdamadi, Ahmad; Moshkdar, Pouya

2016-01-01

Vitamin D (Vit D) is linked to various conditions including musculoskeletal, metabolic and cardiopulmonary diseases. However, it is not clear whether correction of vit D deficiency exerts any beneficial effect in patients with pulmonary hypertension. This study was a prospective uncontrolled longitudinal study. Patients with pulmonary hypertension and vit D deficiency were enrolled into this study. All patients in addition to standard treatment for pulmonary hypertension received cholecalciferol at a dose of 50,000 IU weekly plus calcicare (at a dose of 200 mg magnesium + 8 mg zinc + 400 IU vit D) daily for 3 months. Serum level of 25-hydroxy vit D, serum level of pro-brain natriuretic peptide, six minute walk test (6MWT), peak and mean pulmonary artery pressure, right ventricular size and function, ejection fraction (EF) and New York Heart Association (NYHA) functional class were measured at baseline and after 3 months of treatment. Twenty-two patients with pulmonary hypertension and vit D deficiency were enrolled into the study. At endpoint, the serum vit D level increased significantly to 54.8 ng/ml, the mean of baseline distance of 6MWT increased significantly to 81.6 m and the RV size significantly improved. The mean pulmonary artery pressure also improved after the intervention, but their changes did not reach to statistically significant levels. Vit D replacement therapy in patients with pulmonary arterial hypertension and vit D deficiency results in significant improvement of right ventricular size and 6 MWT. Moreover, mean pulmonary artery pressure improves nonsignificantly. This issue requires further studies with long-term follow-up period.

Systemic Artery to Pulmonary Artery Fistula Associated with Mitral Regurgitation: Successful Treatment with Endovascular Embolization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Iwazawa, Jin, E-mail: iwazawa.jin@nissay-hp.or.j; Nakamura, Kenji; Hamuro, Masao

We present the case of a 60-year-old woman with symptomatic mitral regurgitation caused by a left-to-right shunt via anastomoses consisting of microfistulae, most likely of inflammatory origin, between the right subclavian artery and the right pulmonary artery. The three arteries responsible for fistulous formation, including the internal mammary, thyrocervical, and lateral thoracic arteries, were successfully occluded by transcatheter embolization using superabsorbent polymer microsphere (SAP-MS) particles combined with metallic coils. No complications have been identified following treatment with SAP-MS particles. This approach significantly reduced the patient's mitral regurgitation and she has remained asymptomatic for more than 4 years.

Asymptomatic peripheral artery disease can limit maximal exercise capacity in chronic obstructive pulmonary disease patients regardless of airflow obstruction and lung hyperinflation.

PubMed

Crisafulli, Ernesto; Scelfo, Chiara; Tzani, Panagiota; Aiello, Marina; Bertorelli, Giuseppina; Chetta, Alfredo

2017-06-01

Background Silent/asymptomatic peripheral artery disease may occur in patients with chronic obstructive pulmonary disease, but it is poorly investigated. The primary aim of this study was to evaluate in chronic obstructive pulmonary disease patients the impact of asymptomatic/silent peripheral artery disease on maximal exercise capacity; the secondary aim was to search for predictors of peripheral artery disease. Methods We prospectively enrolled chronic obstructive pulmonary disease outpatients. Data on anthropometric characteristics, lung function, cardiopulmonary exercise test and ankle-brachial index were recorded. The cut-off of ankle-brachial index used to define patients with peripheral artery disease was ≤0.90. Results We studied 47 patients and found 24 patients (51%) who showed peripheral artery disease. As compared to patients without peripheral artery disease, patients with peripheral artery disease had lower values of peak oxygen uptake, peak workload, energy expenditure (metabolic equivalents) and heart rate recovery, but showed the same degree of airflow obstruction and static and dynamic hyperinflation. In a multivariate linear regression model performed to identify variables predicting metabolic equivalents, ankle-brachial index (β 2.59; 95% confidence interval 0.51-4.67; p = 0.016) was an independent variable. In the search for predictors of peripheral artery disease, heart rate recovery (odds ratio 8.80; 95% confidence interval 1.30-59.35; p = 0.026) increased the risk of peripheral artery disease, whereas metabolic equivalents (odds ratio 0.50; 95% confidence interval 0.26-0.94, p = 0.033) and inhaled corticosteroids+long-acting β 2 agonists (odds ratio 0.13; 95% confidence interval 0.02-0.83; p = 0.030) reduced this risk. Conclusions In chronic obstructive pulmonary disease outpatients, asymptomatic/silent peripheral artery disease affects the maximal exercise capacity regardless of airflow obstruction and lung hyperinflation. A delay of heart rate recovery increase the risk of peripheral artery disease, whereas high values of metabolic equivalents and the use of inhaled corticosteroids+long-acting β 2 agonists reduces this risk.

Hemodynamic, pulmonary vascular, and myocardial abnormalities secondary to pharmacologic constriction of the fetal ductus arteriosus. A possible mechanism for persistent pulmonary hypertension and transient tricuspid insufficiency in the newborn infant.

PubMed

Levin, D L; Mills, L J; Weinberg, A G

1979-08-01

The prostaglandin synthetase inhibitor indomethacin was given orally or intravenously to pregnant ewes. This resulted in a significant rise in the fetal pulmonary-to-systemic arterial mean blood pressure difference across the ductus arteriosus, presumably secondary to constriction of the ductus arteriosus. In five experiments the pressure difference could be promptly but temporarily reversed by the administration of prostaglandin E1 (PGE1) into the fetal inferior vena cava. Fetal lungs from study and control animals were fixed by perfusion at measured pulmonary arterial mean blood pressure, and fifth-generation resistance vessels were studied. The medial width/external diameter ratio was significantly increased in the study vs the control lungs due to increased smooth muscle and decreased external diameter. In addition, study fetuses had acute degenerative myocardial changes in the tricuspid valve papillary muscles, the right ventricular free wall and the interventricular septum. Similar changes were not seen in control fetuses. Indomethacin administration during pregnancy causes constriction of the fetal ductus arteriosus, fetal pulmonary arterial hypertension, and right ventricular damage. If severe, this may cause rapid fetal death. If less severe, in the newborn infant, this mechanism may be one cause of persistent pulmonary hypertension due to vasoconstriction and increased pulmonary arterial smooth muscle and/or tricuspid insufficiency due to papillary muscle infarction.

Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Summary of Recommendations.

PubMed

Barberà, Joan Albert; Román, Antonio; Gómez-Sánchez, Miguel Ángel; Blanco, Isabel; Otero, Remedios; López-Reyes, Raquel; Otero, Isabel; Pérez-Peñate, Gregorio; Sala, Ernest; Escribano, Pilar

2018-04-01

Pulmonary hypertension is a hemodynamic disorder defined by abnormally high pulmonary artery pressure that can occur in numerous diseases and clinical situations. The causes of pulmonary hypertension are classified into 5 major groups: arterial, due to left heart disease, due to lung disease and/or hypoxemia, chronic thromboembolic, with unclear and/or multifactorial mechanisms. This is a brief summary of the Guidelines on the Diagnostic and Treatment of Pulmonary Hypertension of the Spanish Society of Pulmonology and Thoracic Surgery. These guidelines describe the current recommendations for the diagnosis and treatment of the different pulmonary hypertension groups. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Pulse oximetry in the pulmonary tissue for the non-invasive measurement of mixed venous oxygen saturation.

PubMed

Nitzan, Meir; Nitzan, Itamar

2013-08-01

The oxygen saturation of the systemic arterial blood is associated with the adequacy of respiration, and can be measured non-invasively by pulse oximetry in the systemic tissue. The oxygen saturation of the blood in the pulmonary artery, the mixed venous blood, reflects the balance between oxygen supply to the systemic tissues and their oxygen demand. The mixed venous oxygen saturation has also clinical significance because it is used in Fick equation for the quantitative measurement of cardiac output. At present the measurement of the mixed venous oxygen saturation is invasive and requires insertion of a Swan-Ganz catheter into the pulmonary artery. We suggest a noninvasive method for the measurement of the mixed venous oxygen saturation in infants, pulmonary pulse oximetry. The method is similar to the systemic pulse oximetry, which is based on the different light absorption curves of oxygenated and deoxygenated hemoglobin and on the analysis of photoplethysmographic curves in two wavelengths. The proposed pulmonary pulse oximeter includes light-sources of two wavelengths in the infrared, which illuminate the pulmonary tissue through the thoracic wall. Part of the light which is scattered back from the pulmonary tissue and passes through the thoracic wall is detected, and for each wavelength a pulmonary photoplethysmographic curve is obtained. The pulmonary photoplethysmographic curves reflect blood volume increase during systole in the pulmonary arteries in the lung tissue, which contain mixed venous blood. The ratio R of the amplitude-to-baseline ratio for the two wavelengths is related to the mixed venous oxygen saturation through equations derived for the systemic pulse oximetry. The method requires the use of extinction coefficients values for oxygenated and deoxygenated hemoglobin, which can be found in the literature. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pulmonary hypertension due to acute respiratory distress syndrome

PubMed Central

Ñamendys-Silva, S.A.; Santos-Martínez, L.E.; Pulido, T.; Rivero-Sigarroa, E.; Baltazar-Torres, J.A.; Domínguez-Cherit, G.; Sandoval, J.

2014-01-01

Our aims were to describe the prevalence of pulmonary hypertension in patients with acute respiratory distress syndrome (ARDS), to characterize their hemodynamic cardiopulmonary profiles, and to correlate these parameters with outcome. All consecutive patients over 16 years of age who were in the intensive care unit with a diagnosis of ARDS and an in situ pulmonary artery catheter for hemodynamic monitoring were studied. Pulmonary hypertension was diagnosed when the mean pulmonary artery pressure was >25 mmHg at rest with a pulmonary artery occlusion pressure or left atrial pressure <15 mmHg. During the study period, 30 of 402 critically ill patients (7.46%) who were admitted to the ICU fulfilled the criteria for ARDS. Of the 30 patients with ARDS, 14 met the criteria for pulmonary hypertension, a prevalence of 46.6% (95% CI; 28-66%). The most common cause of ARDS was pneumonia (56.3%). The overall mortality was 36.6% and was similar in patients with and without pulmonary hypertension. Differences in patients' hemodynamic profiles were influenced by the presence of pulmonary hypertension. The levels of positive end-expiratory pressure and peak pressure were higher in patients with pulmonary hypertension, and the PaCO2 was higher in those who died. The level of airway pressure seemed to influence the onset of pulmonary hypertension. Survival was determined by the severity of organ failure at admission to the intensive care unit. PMID:25118626

A Novel Therapeutic Approach in the Treatment of Pulmonary Arterial Hypertension: Allium ursinum Liophylisate Alleviates Symptoms Comparably to Sildenafil

PubMed Central

Bombicz, Mariann; Priksz, Daniel; Varga, Balazs; Kurucz, Andrea; Kertész, Attila; Takacs, Akos; Posa, Aniko; Kiss, Rita; Szilvassy, Zoltan; Juhasz, Bela

2017-01-01

Right-sided heart failure—often caused by elevated pulmonary arterial pressure—is a chronic and progressive condition with particularly high mortality rates. Recent studies and our current findings suggest that components of Wild garlic (Allium ursinum, AU) may play a role in reducing blood pressure, inhibiting angiotensin-converting enzyme (ACE), as well as improving right ventricle function in rabbit models with heart failure. We hypothesize that AU may mitigate cardiovascular damage caused by pulmonary arterial hypertension (PAH) and has value in the supplementary treatment of the complications of the disease. In this present investigation, PAH was induced by a single dose of monocrotaline (MCT) injection in Sprague-Dawley rats, and animals were divided into 4 treatment groups as follows: I. healthy control animals (Control group); II. pulmonary hypertensive rats (PAH group); III. pulmonary hypertensive rats + daily sildenafil treatment (Sildenafil group); and IV. pulmonary hypertensive rats + Wild garlic liophylisate-enriched chow (WGLL group), for 8 weeks. Echocardiographic measurements were obtained on the 0 and 8 weeks with fundamental and Doppler imaging. Isolated working heart method was used to determinate cardiac functions ex vivo after thoracotomy on the 8th week. Histological analyses were carried out on excised lung samples, and Western blot technique was used to determine Phosphodiesterase type 5 enzyme (PDE5) expression in both myocardial and pulmonary tissues. Our data demonstrate that right ventricle function measured by echocardiography was deteriorated in PAH animals compared to controls, which was counteracted by AU treatment. Isolated working heart measurements showed elevated aortic flow in WGLL group compared to PAH animals. Histological analysis revealed dramatic increase in medial wall thickness of pulmonary arteries harvested from PAH animals, but arteries of animals in sildenafil- and WGLL-treated groups showed physiological status. Our results suggest that bioactive compounds in Allium ursinum could have beneficial effects in pulmonary hypertension. PMID:28677661

Galectin-3: A Link between Myocardial and Arterial Stiffening in Patients with Acute Decompensated Heart Failure?

PubMed

Lala, Radu Ioan; Darabantiu, Dan; Pilat, Luminita; Puschita, Maria

2016-02-01

Heart failure is accompanied by abnormalities in ventricular-vascular interaction due to increased myocardial and arterial stiffness. Galectin-3 is a recently discovered biomarker that plays an important role in myocardial and vascular fibrosis and heart failure progression. The aim of this study was to determine whether galectin-3 is correlated with arterial stiffening markers and impaired ventricular-arterial coupling in decompensated heart failure patients. A total of 79 inpatients with acute decompensated heart failure were evaluated. Serum galectin-3 was determined at baseline, and during admission, transthoracic echocardiography and measurements of vascular indices by Doppler ultrasonography were performed. Elevated pulse wave velocity and low arterial carotid distensibility are associated with heart failure in patients with preserved ejection fraction (p = 0.04, p = 0.009). Pulse wave velocity, carotid distensibility and Young's modulus did not correlate with serum galectin-3 levels. Conversely, raised galectin-3 levels correlated with an increased ventricular-arterial coupling ratio (Ea/Elv) p = 0.047, OR = 1.9, 95% CI (1.0‑3.6). Increased galectin-3 levels were associated with lower rates of left ventricular pressure rise in early systole (dp/dt) (p=0.018) and raised pulmonary artery pressure (p = 0.046). High galectin-3 levels (p = 0.038, HR = 3.07) and arterial pulmonary pressure (p = 0.007, HR = 1.06) were found to be independent risk factors for all-cause mortality and readmissions. This study showed no significant correlation between serum galectin-3 levels and arterial stiffening markers. Instead, high galectin-3 levels predicted impaired ventricular-arterial coupling. Galectin-3 may be predictive of raised pulmonary artery pressures. Elevated galectin-3 levels correlate with severe systolic dysfunction and together with pulmonary hypertension are independent markers of outcome.

Novel therapeutic approach for pulmonary emphysema using gelatin microspheres releasing basic fibroblast growth factor in a canine model.

PubMed

Chang, Sung Soo; Yokomise, Hiroyasu; Matsuura, Natsumi; Gotoh, Masashi; Tabata, Yasuhiko

2014-08-01

The prognosis of patients with emphysema is poor as there is no truly effective treatment. Our previous study showed that the alveolar space was smaller and the microvessel density was higher in a canine emphysema model after the intrapulmonary arterial administration of gelatin microspheres slowly releasing basic fibroblast growth factor (bFGF-GMS). In the present study, we evaluated the functional effect of injecting bFGF-GMS via the pulmonary artery in this canine pulmonary emphysema model. Using the porcine pancreatic elastase (PPE)-induced total emphysema model, we approximated the value of lung compliance with a Power Lab System, and performed blood gas analysis in a control group, a total emphysema group, and a bFGF group in which bFGF-GMS were injected toward the whole pulmonary artery via the femoral vein. Each group comprised five dogs. Lung compliance was higher in the total emphysema group than in the control group (p = 0.031), and the bFGF group showed no significant improvement of lung compliance vs. the total emphysema group (p = 0.112). PaO2 (partial pressure of oxygen in arterial blood) was improved by administering bFGF-GMS in the total emphysema model (p = 0.027). In the canine total emphysema model, blood gas parameters were improved by the whole pulmonary arterial administration of bFGF-GMS. This method has the potential to be an effective novel therapy for pulmonary emphysema.

Pulmonary veins in the normal lung and pulmonary hypertension due to left heart disease

PubMed Central

Hunt, James M.; Bethea, Brian; Liu, Xiang; Gandjeva, Aneta; Mammen, Pradeep P. A.; Stacher, Elvira; Gandjeva, Marina R.; Parish, Elisabeth; Perez, Mario; Smith, Lynelle; Graham, Brian B.; Kuebler, Wolfgang M.

2013-01-01

Despite the importance of pulmonary veins in normal lung physiology and the pathobiology of pulmonary hypertension with left heart disease (PH-LHD), pulmonary veins remain largely understudied. Difficult to identify histologically, lung venous endothelium or smooth muscle cells display no unique characteristic functional and structural markers that distinguish them from pulmonary arteries. To address these challenges, we undertook a search for unique molecular markers in pulmonary veins. In addition, we addressed the expression pattern of a candidate molecular marker and analyzed the structural pattern of vascular remodeling of pulmonary veins in a rodent model of PH-LHD and in lung tissue of patients with PH-LHD obtained at time of placement on a left ventricular assist device. We detected urokinase plasminogen activator receptor (uPAR) expression preferentially in normal pulmonary veins of mice, rats, and human lungs. Expression of uPAR remained elevated in pulmonary veins of rats with PH-LHD; however, we also detected induction of uPAR expression in remodeled pulmonary arteries. These findings were validated in lungs of patients with PH-LHD. In selected patients with sequential lung biopsy at the time of removal of the left ventricular assist device, we present early data suggesting improvement in pulmonary hemodynamics and venous remodeling, indicating potential regression of venous remodeling in response to assist device treatment. Our data indicate that remodeling of pulmonary veins is an integral part of PH-LHD and that pulmonary veins share some key features present in remodeled yet not normotensive pulmonary arteries. PMID:24039255

[Pulmonary thromboembolism. Therapy recommendations of the practice guidelines of the Mexican Society of Cardiology].

PubMed

Jerjes-Sánchez, Carlos; Ramírez-Rivera, Alicia

2007-01-01

Prevalence and incidence of pulmonary thromboembolism (PTE) is very high, and in many cases, remains undiagnosed. In developed countries, it's the third cause of cardiovascular mortality, a fact that is also observed in developing countries. Within the clinical spectrum, PTE is regarded as minor and massive, in between a sub-massive PET, which is characterized by normal arterial pressure, or even hypotension, with compensated systemic perfusion and right ventricle dysfunction (RVD), with presence or not or positive biomarkers. When there is no evidence of severe pulmonary hypertension, or RVD, anticoagulation therapy stands as the pharmacological approach. When RVD is observed, pulmonary reperfusion is advised. According to the guidelines and recommendations for stratification, diagnose, and treatment of PTE, from the Pulmonary Circulation Chapter of the Mexican Society of Cardiology, evidence is established between physiopathology and the degree of vascular pulmonary obstruction.

[The heart catheter table is not the operating table : Intraindividual comparison of pulmonary artery pressures].

PubMed

Ziegler, M U; Reinelt, H

2018-05-01

Patients undergoing cardiac surgery need extensive and invasive monitoring, which needs to be individually adapted for each patient and requires a diligent risk-benefit analysis. The use of a pulmonary artery catheter (PAC) seems to be justifiable in certain cases; therefore, the preoperative diagnosis of pulmonary hypertension represents an indication for perioperative monitoring with PAC in the S3 guidelines of the German Society for Anesthesiology and Intensive Care Medicine (DGAI). In many cases, however, this preoperative diagnosis cannot be confirmed intraoperatively. We wanted to find out whether this is just an impression or whether there actually are significant differences between preoperative, intraoperative and postoperative pulmonary artery pressures. After obtaining ethical approval, we retrospectively compared the pulmonary pressures of cardiac surgery patients with an elevated pulmonary pressure during preoperative right heart catheterization with those obtained intraoperatively and postoperatively by means of a PAC. All patients with a preoperatively documented pulmonary artery pressure of 40 mmHg or above and an intraoperative use of a PAC during a 4-year period were included. Exclusion criteria were intracardiac shunts, cardiogenic shock, emergency procedures, pulmonary hypertension of non-cardiac origin and a time span of more than 1 year between right heart catheterization and surgery. We included 90 patients. In the whole group and in the subgroups (according to diagnosis, time elapsed between heart catheterization and operation and pulmonary pressure), there were significant differences between preoperative and intraoperative pulmonary and systemic pressures. Systemic and pulmonary artery pressures were significantly higher during preoperative catheterization than intraoperatively. The systemic systolic pressure/systolic pulmonary pressure ratio, however, remained constant. The intraoperative and postoperative systemic and pulmonary artery pressures showed no significant differences. As a normal ejection fraction does not exclude heart failure with preserved ejection fraction and as we did not have any information on this condition, we did not group the patients according to the ejection fraction. An elevated pulmonary pressure obtained preoperatively during right heart catheterization is not indicative of an elevated pulmonary pressure either intraoperatively or postoperatively. There are various explanations for the differences (e.g., different physiological and pathophysiological settings, such as sedation with potential hypercapnia versus anesthesia with vasodilation when measured; newly prescribed medication coming into effect between the right heart catheterization and surgery; intraoperative positioning). Even though the inherent risks of a PAC seem to be low, we recommend refraining from using a PAC in patients with a once documented elevated pulmonary pressure by default. As an alternative we suggest estimating the pulmonary pressure by transesophageal echocardiography (TEE) as an aid to decide whether the patient will benefit from the use of a PAC. Especially if it is not possible to identify tricuspid valve regurgitation for determining the peak gradient, it is helpful to check for additional signs of pulmonary hypertension. But we also have to bear in mind that in the postoperative period only a PAC can provide continuous measurement of pulmonary pressure.

Anomalous Left Coronary Artery from the Pulmonary Artery: Masquerading as Peripartum Cardiomyopathy.

PubMed

Frigault, Jonathan; Lafrenière-Bessi, Valérie; Perron, Jean; Bédard, Élisabeth; Philippon, François; Poirier, Paul; Larose, Éric; Jacques, Frédéric

2018-03-09

Diagnosed with peripartum cardiomyopathy 8 years earlier, a 45-year-old female suffered sudden cardiac death. Following resuscitation, the patient was diagnosed with an anomalous origin of the left coronary artery from the pulmonary artery and underwent a successful coronary repair. The management of a patient with clinical features of cardiomyopathy is reviewed. Anomalous left coronary artery originating from the pulmonary artery (ALCAPA) is a rare but potentially lethal congenital anomaly affecting 1 in 300,000 live births 1 . Infants may have clinical features of myocardial ischemia and congestive heart failure 2 . Most surgically untreated patients die within the first year of life 3 . Although rare in teenagers and adults, this syndrome can cause sudden cardiac death 3 . ALCAPA that becomes clinically significant in the peripartum period and that is misdiagnosed for a postpartum cardiomyopathy, such as presented herein, is a very rare occurrence. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Reliability of temperatures measured at standard monitoring sites as an index of brain temperature during deep hypothermic cardiopulmonary bypass conducted for thoracic aortic reconstruction.

PubMed

Akata, Takashi; Setoguchi, Hidekazu; Shirozu, Kazuhiro; Yoshino, Jun

2007-06-01

It is essential to estimate the brain temperature of patients during deliberate deep hypothermia. Using jugular bulb temperature as a standard for brain temperature, we evaluated the accuracy and precision of 5 standard temperature monitoring sites (ie, pulmonary artery, nasopharynx, forehead deep-tissue, urinary bladder, and fingertip skin-surface tissue) during deep hypothermic cardiopulmonary bypass conducted for thoracic aortic reconstruction. In 20 adult patients with thoracic aortic aneurysms, the 5 temperature monitoring sites were recorded every 1 minute during deep hypothermic (<20 degrees C) cardiopulmonary bypass. The accuracy was evaluated by the difference from jugular bulb temperature, and the precision was evaluated by its standard deviation, as well as by the correlation with jugular bulb temperature. Pulmonary artery temperature and jugular bulb temperature began to change immediately after the start of cooling or rewarming, closely matching each other, and the other temperatures lagged behind these two temperatures. During either situation, the accuracy of pulmonary artery temperature measurement (0.3 degrees C-0.5 degrees C) was much superior to the other measurements, and its precision (standard deviation of the difference from jugular bulb temperature = 1.5 degrees C-1.8 degrees C; correlation coefficient = 0.94-0.95) was also best among the measurements, with its rank order being pulmonary artery > or = nasopharynx > forehead > bladder > fingertip. However, the accuracy and precision of pulmonary artery temperature measurement was significantly impaired during and for several minutes after infusion of cold cardioplegic solution. Pulmonary artery temperature measurement is recommended to estimate brain temperature during deep hypothermic cardiopulmonary bypass, even if it is conducted with the sternum opened; however, caution needs to be exercised in interpreting its measurements during periods of the cardioplegic solution infusion.

Lung Abscess as Delayed Manifestation of Pulmonary Arterial Narrowing After Sleeve Resection.

PubMed

Frenzen, Frederik S; Lesser, Thomas; Platzek, Ivan; Riede, Frank-Thomas; Kolditz, Martin

2017-08-01

A patient who had undergone right upper bilobectomy because of a carcinoid experienced lung abscesses 17 months after operation. After recurrences, despite different antibiotic agents, dual-energy computed tomography showed subtotal stenosis of the right lower lobe pulmonary artery with marked pulmonary perfusion-reduction. Rare causes of lung-abscesses should be considered. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

BMP type II receptor as a therapeutic target in pulmonary arterial hypertension.

PubMed

Orriols, Mar; Gomez-Puerto, Maria Catalina; Ten Dijke, Peter

2017-08-01

Pulmonary arterial hypertension (PAH) is a chronic disease characterized by a progressive elevation in mean pulmonary arterial pressure. This occurs due to abnormal remodeling of small peripheral lung vasculature resulting in progressive occlusion of the artery lumen that eventually causes right heart failure and death. The most common cause of PAH is inactivating mutations in the gene encoding a bone morphogenetic protein type II receptor (BMPRII). Current therapeutic options for PAH are limited and focused mainly on reversal of pulmonary vasoconstriction and proliferation of vascular cells. Although these treatments can relieve disease symptoms, PAH remains a progressive lethal disease. Emerging data suggest that restoration of BMPRII signaling in PAH is a promising alternative that could prevent and reverse pulmonary vascular remodeling. Here we will focus on recent advances in rescuing BMPRII expression, function or signaling to prevent and reverse pulmonary vascular remodeling in PAH and its feasibility for clinical translation. Furthermore, we summarize the role of described miRNAs that directly target the BMPR2 gene in blood vessels. We discuss the therapeutic potential and the limitations of promising new approaches to restore BMPRII signaling in PAH patients. Different mutations in BMPR2 and environmental/genetic factors make PAH a heterogeneous disease and it is thus likely that the best approach will be patient-tailored therapies.

Pulmonary Hypertension Overview

MedlinePlus

... well as sleep apnea, are common causes of secondary pulmonary hypertension. Other causes include the following: Congestive heart failure Birth defects in the heart Chronic pulmonary thromboembolism (blood clots in the pulmonary arteries) Acquired immunodeficiency syndrome ( ...

[Two stage surgical treatment of large ventricular septal defects (author's transl)].

PubMed

Hoffmeister, H E; Seybold-Epting, W; Stunkat, R

1976-12-01

Since March 1971, 51 infants were subjected to pulmonary artery banding (PAB) for a large ventricular septal defect (VSD) with pulmonary hypertension. 41 infants (80%) were under six months of age. Additional defects were present in 41%. Twelve babies died (24%). The lowest mortality was achieved in isolated VSD (6,7%). 28 patients subsequently underwent VSD closure and pulmonary artery debanding. Catheterization data revealed normal or slightly elevated pressures and normal vascular resistance in the pulmonary circuit in 22 children. The operative mortality rate was 10,7%.

Measurement of pulmonary arterial impedance and reflection from single-slice phase-contrast and steady-state free precession MRI

NASA Astrophysics Data System (ADS)

Leimbigler, Peter John

Pulmonary arterial hypertension (PAH) alters vessel wall mechanics and vasomotor tone, driving up pulmonary hemodynamic variables such as pulse wave velocity, input and characteristic impedance, and pulse wave reflection magnitude. Heterogeneous treatment response necessitates frequent hemodynamic evaluation, for which right-heart catheterization (RHC) remains the gold standard; however, several disadvantages limit its frequency of use. In this work, a non-invasive magnetic resonance (MR) imaging protocol is developed to address the shortcomings of invasive hemodynamic monitoring and may support existing diagnostic procedures. First, accuracy and precision of the proposed method is characterized through linear uncertainty propagation and numerical simulation of the data-processing pipeline. Second, the MR protocol is tested in seven healthy adult volunteers. Third, a rapid version of the MR protocol is tested in a healthy volunteer, yielding good agreement with mean values obtained in the seven-volunteer study.

Potential use of TNF-α inhibitors in systemic sclerosis.

PubMed

Murdaca, Giuseppe; Spanò, Francesca; Contatore, Miriam; Guastalla, Andrea; Puppo, Francesco

2014-01-01

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by chronic inflammation and fibrosis of the skin, vascular abnormalities and variable involvement of organs. TNF-α has a central role in initial host response to infections and in the pathogenesis of various systemic immune-mediated diseases. Serum levels of TNF-α are elevated in patients with SSc and favor the development of pulmonary fibrosis and pulmonary arterial hypertension. Inflammatory arthritis can occur in patients with SSc. Infliximab and etanercept may improve the inflammatory arthritis and disability in SSc. TNF-α inhibitors reduce the systemic inflammation, improve the endothelial function decreasing the risk of pulmonary arterial hypertension progression and of acute cardiovascular and/or cerebrovascular events. Physicians need to be aware of the potential risks of tuberculosis reactivation and opportunistic infections. Randomized controlled trials with TNF-α inhibitors in patients with SSc are needed to confirm the potential role of these agents in the treatment of SSc.

Chronic thrombotic obstruction of major pulmonary arteries : report of a case successfully treated by thrombendarterectomy, and a review of the literature.

DOT National Transportation Integrated Search

1963-08-01

A case is reported of chronic massive thromboembolic occlusion of major pulmonary arterial branches successfully treated with embolectomy and endarterectomy. The historic features, physical signs and pathophysiologic alterations which form the basis ...

URBAN PARTICLE-INDUCED PULMONARY ARTERY CONSTRUCTION IS MEDIATED BY SUPEROXIDE PRODUCTION

EPA Science Inventory

URBAN PARTICLE-INDUCED PULMONARY ARTERY CONSTRICTION IS MEDIATED BY SUPEROXIDE PRODUCTION.Jacqueline D. Carter, Zhuowei Li, Lisa A. Dailey, Yuh-Chin T. Huang. CEMALB, University of North Carolina, and ORD, US EPA, Chapel Hill, North Carolina.

Exposure to particulate matter...

Brief report: effect of ambrisentan treatment on exercise-induced pulmonary hypertension in systemic sclerosis: a prospective single-center, open-label pilot study.

PubMed

Saggar, Rajeev; Khanna, D; Shapiro, S; Furst, D E; Maranian, P; Clements, P; Abtin, F; Dua, Shiv; Belperio, J; Saggar, Rajan

2012-12-01

Exercise-induced pulmonary hypertension (ePH) may represent an early, clinically relevant phase in the spectrum of pulmonary vascular disease. The purpose of this pilot study was to describe the changes in hemodynamics and exercise capacity in patients with systemic sclerosis (SSc) spectrum-associated ePH treated with open-label daily ambrisentan. Patients were treated with ambrisentan, 5 mg or 10 mg once daily, for 24 weeks. At baseline and 24 weeks, patients with SSc spectrum disorders exercised in a supine position, on a lower extremity cycle ergometer. All patients had normal hemodynamics at rest. We defined baseline ePH as a mean pulmonary artery pressure of >30 mm Hg with maximum exercise and a transpulmonary gradient (TPG) of >15 mm Hg. The primary end point was change in pulmonary vascular resistance (PVR) with exercise. Secondary end points included an improvement from baseline in 6-minute walking distance, health-related quality of life assessments, and cardiopulmonary hemodynamics. Of the 12 enrolled patients, 11 completed the study. At 24 weeks there were improvements in mean exercise PVR (85.8 dynes × second/cm(5) ; P = 0.003) and mean distance covered during 6-minute walk (44.5 meters; P = 0.0007). Improvements were also observed in mean exercise cardiac output (1.4 liters/minute; P = 0.006), mean pulmonary artery pressure (-4.1 mm Hg; P = 0.02), and total pulmonary resistance (-93.0 dynes × seconds/cm(5) ; P = 0.0008). Three patients developed resting pulmonary arterial hypertension during the 24 weeks. Exercise hemodynamics and exercise capacity in patients with SSc spectrum-associated ePH improved over 24 weeks with exposure to ambrisentan. Placebo-controlled studies are needed to confirm whether this is a drug-related effect and to determine optimal therapeutic regimens for patients with ePH. Copyright © 2012 by the American College of Rheumatology.

Phasic negative intrathoracic pressures enhance the vascular responses to stimulation of pulmonary arterial baroreceptors in closed-chest anaesthetized dogs

PubMed Central

Moore, Jonathan P; Hainsworth, Roger; Drinkhill, Mark J

2004-01-01

We investigated whether the reflex responses to stimulation of pulmonary arterial baroreceptors were altered by intrathoracic pressure changes similar to those encountered during normal breathing. Dogs were anaesthetized with α-chloralose, a cardiopulmonary bypass was established, and the pulmonary trunk and its main branches as far as the first lobar arteries were vascularly isolated and perfused with venous blood. The chest was closed following connection to the perfusion circuit and pressures distending the aortic arch, carotid sinus and coronary artery baroreceptors were controlled. Changes in the descending aortic (systemic) perfusion pressure (SPP; flow constant) were used to assess changes in systemic vascular resistance. Values of SPP were plotted against mean pulmonary arterial pressure (PAP) and sigmoid functions applied. From these curves we derived the threshold pressures (corresponding to 5% of the overall response of SPP), the maximum slopes (equivalent to peak gain) and the corresponding PAP (equivalent to ‘set point’). Stimulus–response curves were compared between data obtained with intrathoracic pressure at atmospheric and with a phasic intrathoracic pressure ranging from atmospheric to around −10 mmHg (18 cycles min−1). Results were obtained from seven dogs and are given as means ±s.e.m. Compared to the values obtained when intrathoracic pressure was at atmospheric, the phasic intrathoracic pressure decreased the pulmonary arterial threshold pressure in five dogs; average change from 28.4 ± 5.9 to 19.3 ± 5.9 mmHg (P > 0.05). The inflexion pressure was significantly reduced from 37.8 ± 4.8 to 27.4 ± 4.0 mmHg (P < 0.03), but the slopes of the curves were not consistently changed. These results have shown that a phasic intrathoracic pressure, which simulates respiratory oscillations, displaces the stimulus–response curve of the pulmonary arterial baroreceptors to lower pressures so that it lies within a physiological range of pressures. PMID:14724182

Exercise facilitates early recognition of cardiac and vascular remodeling in chronic thromboembolic pulmonary hypertension in swine.

PubMed

Stam, Kelly; van Duin, Richard W B; Uitterdijk, André; Cai, Zongye; Duncker, Dirk J; Merkus, Daphne

2018-03-01

Chronic thromboembolic pulmonary hypertension (CTEPH) develops in 4% of patients after pulmonary embolism and is accompanied by an impaired exercise tolerance, which is ascribed to the increased right ventricular (RV) afterload in combination with a ventilation/perfusion (V/Q) mismatch in the lungs. The present study aimed to investigate changes in arterial Po 2 and hemodynamics in response to graded treadmill exercise during development and progression of CTEPH in a novel swine model. Swine were chronically instrumented and received multiple pulmonary embolisms by 1) microsphere infusion (Spheres) over 5 wk, 2) endothelial dysfunction by administration of the endothelial nitric oxide synthase inhibitor N ω -nitro-l-arginine methyl ester (L-NAME) for 7 wk, 3) combined pulmonary embolisms and endothelial dysfunction (L-NAME + Spheres), or 4) served as sham-operated controls (sham). After a 9 wk followup, embolization combined with endothelial dysfunction resulted in CTEPH, as evidenced by mean pulmonary artery pressures of 39.5 ± 5.1 vs. 19.1 ± 1.5 mmHg (Spheres, P < 0.001), 22.7 ± 2.0 mmHg (L-NAME, P < 0.001), and 20.1 ± 1.5 mmHg (sham, P < 0.001), and a decrease in arterial Po 2 that was exacerbated during exercise, indicating V/Q mismatch. RV dysfunction was present after 5 wk of embolization, both at rest (trend toward increased RV end-systolic lumen area, P = 0.085, and decreased stroke volume index, P = 0.042) and during exercise (decreased stroke volume index vs. control, P = 0.040). With sustained pulmonary hypertension, RV hypertrophy (Fulton index P = 0.022) improved RV function at rest and during exercise, but this improvement was insufficient in CTEPH swine to result in an exercise-induced increase in cardiac index. In conclusion, embolization in combination with endothelial dysfunction results in CTEPH in swine. Exercise increased RV afterload, exacerbated the V/Q mismatch, and unmasked RV dysfunction. NEW & NOTEWORTHY Here, we present the first double-hit chronic thromboembolic pulmonary hypertension swine model. We show that embolization as well as endothelial dysfunction is required to induce sustained pulmonary hypertension, which is accompanied by altered exercise hemodynamics and an exacerbated ventilation/perfusion mismatch during exercise.

Structure and composition of pulmonary arteries, capillaries and veins

PubMed Central

2013-01-01

The pulmonary vasculature is comprised of three anatomic compartments connected in series: the arterial tree, an extensive capillary bed, and the venular tree. Although in general this vasculature is thin-walled, structure is nonetheless complex. Contributions to structure (and thus potentially to function) from cells other than endothelial and smooth muscle cells as well as those from the extracellular matrix should be considered. This review is multifaceted, bringing together information regarding 1) classification of pulmonary vessels, 2) branching geometry in the pulmonary vascular tree, 3) a quantitative view of structure based on morphometry of the vascular wall, 4) the relationship of nerves, a variety of interstitial cells, matrix proteins, and striated myocytes to smooth muscle and endothelium in the vascular wall, 5) heterogeneity within cell populations and between vascular compartments, 6) homo- and heterotypic cell-cell junctional complexes, and 7) the relation of the pulmonary vasculature to that of airways. These issues for pulmonary vascular structure are compared, when data is available, across species from human to mouse and shrew. Data from studies utilizing vascular casting, light and electron microscopy, as well as models developed from those data, are discussed. Finally, the need for rigorous quantitative approaches to study of vascular structure in lung is highlighted. PMID:23606929

Impact of the mitochondria-targeted antioxidant MitoQ on hypoxia-induced pulmonary hypertension.

PubMed

Pak, Oleg; Scheibe, Susan; Esfandiary, Azadeh; Gierhardt, Mareike; Sydykov, Akylbek; Logan, Angela; Fysikopoulos, Athanasios; Veit, Florian; Hecker, Matthias; Kroschel, Florian; Quanz, Karin; Erb, Alexandra; Schäfer, Katharina; Fassbinder, Mirja; Alebrahimdehkordi, Nasim; Ghofrani, Hossein A; Schermuly, Ralph T; Brandes, Ralf P; Seeger, Werner; Murphy, Michael P; Weissmann, Norbert; Sommer, Natascha

2018-02-01

Increased mitochondrial reactive oxygen species (ROS), particularly superoxide have been suggested to mediate hypoxic pulmonary vasoconstriction (HPV), chronic hypoxia-induced pulmonary hypertension (PH) and right ventricular (RV) remodelling.We determined ROS in acute, chronic hypoxia and investigated the effect of the mitochondria-targeted antioxidant MitoQ under these conditions.The effect of MitoQ or its inactive carrier substance, decyltriphenylphosphonium (TPP + ), on acute HPV (1% O 2 for 10 minutes) was investigated in isolated blood-free perfused mouse lungs. Mice exposed for 4 weeks to chronic hypoxia (10% O 2 ) or after banding of the main pulmonary artery (PAB) were treated with MitoQ or TPP + (50 mg/kg/day).Total cellular superoxide and mitochondrial ROS levels were increased in pulmonary artery smooth muscle cells (PASMC), but decreased in pulmonary fibroblasts in acute hypoxia. MitoQ significantly inhibited HPV and acute hypoxia-induced rise in superoxide concentration. ROS was decreased in PASMC, while it increased in the RV after chronic hypoxia. Correspondingly, MitoQ did not affect the development of chronic hypoxia-induced PH, but attenuated RV remodelling after chronic hypoxia as well as after PAB.Increased mitochondrial ROS of PASMC mediate acute HPV, but not chronic hypoxia-induced PH. MitoQ may be beneficial under conditions of exaggerated acute HPV. Copyright ©ERS 2018.

Simultaneous transcatheter closure of intralobar pulmonary sequestration and patent ductus arteriosus in a patient with infantile Scimitar syndrome.

PubMed

Aslan, Eyüp; Tanıdır, İbrahim Cansaran; Saygı, Murat; Onan, Sertaç Hanedan; Güzeltaş, Alper

2015-03-01

Scimitar syndrome is a rare disease associated with a right lung sequestration vascularised by arteries arising from the abdominal aorta and abnormal venous drainage into the inferior vena cava. The infantile form is generally presented with severe heart failure, pulmonary hypertension and respiratory distress. It may be associated with various intracardiac defects, including atrial septal defects, ventricular septal defects, patent ductus arteriosus or more complicated structural congenital heart defects. Here, we present a 2-month-old girl with Scimitar syndrome whose pulmonary arterial pressure decreased after transcatheter patent ductus arteriosus closure and embolization of the anomalous systemic arterial supply.

Continuous recording of pulmonary artery pressure in unrestricted subjects.

PubMed Central

Ikram, H; Richards, A M; Hamilton, E J; Nicholls, M G

1984-01-01

Continuous ambulatory pulmonary artery pressures were recorded using a conventional No 5 French Goodale-Lubin filled catheter linked to the Oxford Medilog system of a portable transducer-perfusion unit and miniaturised recorder. Data retrieval and analysis were performed using a PB2 Medilog playback unit linked to a PDP 11 computer system. The total system has a frequency response linear to 8 Hz allowing accurate pressure recording over the full range of heart rates. Ten recordings in 10 patients yielded artefact free data for 80% or more of the recorded period. This inexpensive reliable method allows pulmonary artery pressures to be recorded in unrestricted subjects. Images PMID:6704262

Anomalous left coronary artery from the pulmonary artery with a large patent ductus arteriosus: aversion of a catastrophe.

PubMed

Aggarwal, Sanjeev; Delius, Ralph E; Pettersen, Michael D

2013-01-01

We present an infant who had an anomalous left coronary artery arising from the pulmonary artery (ALCAPA) and a large patent ductus arteriosus (PDA), who was diagnosed before a potentially catastrophic closure of PDA. In the presence of normal left ventricular function and the absence of coronary artery collaterals, it is difficult to diagnose ALCAPA. A disproportionate degree of left ventricular dilation and severity of mitral valve regurgitation relative to the degree of PDA shunt, and echogenic papillary muscles on an echocardiogram should raise a suspicion of coronary artery anomalies. The infant underwent surgical ligation of PDA with translocation of coronary arteries and had an uneventful recovery. © 2012 Wiley Periodicals, Inc.

Expression of angiogenic factors and plexiform lesions in the lungs of broiler and layer chickens: A comparison.

PubMed

Tan, X; Shao, F-J; Fan, G-J; Ying, Y-T

2018-05-01

Plexiform lesions are characteristic histological changes of pulmonary arteries in human patients with severe pulmonary arterial hypertension (PAH) and are regarded as angiogenic lesions. Meat-type broiler chickens are susceptible to PAH and can develop plexiform lesions spontaneously. Whether the lesion development in broilers is associated with PAH predisposition and lung angiogenic environment remains unclear. Moreover, little is known about the cellular origin of these structures. In this work, plexiform lesions were detected in both layer chickens (a strain known to be resistant to PAH) and broiler chickens aged between 1 and 6 wk with normal pulmonary arterial pressures. Within each of the sampled ages, the lesion density did not differ between strains, with an exception of wk 4 when broiler was higher than layer. In contrast to the trend of age-related decline in layers, lesion densities in broilers demonstrated bi-phasic alterations characterized by a gradual decrease during wk 1 to 3 followed by a sudden increase at wk 4. The mRNA of 6 angiogenic factors in the lung tissue, namely, vascular endothelial growth factor receptor (VEGFR)-2, angiopoietin (Ang)-1, angiopoietin receptor Tie-2, transforming growth factor (TGF)-β1, hepatocyte growth factor (HGF), and interleukin (IL)-8, were differentially expressed between strains. However, none of them was found to be significantly correlated with the lesion density by strain and age-adjusted partial correlation analysis. An in vivo experiment revealed impaired differentiation of endothelial progenitor cells (EPC) into endothelial cells during the producing of plexiform lesions, as evidenced by increased expression of endothelial CD133, a maker of EPC, but reduced expression of CD31, a marker of mature endothelial cells, in the parent vessels of plexiform lesions compared to normal vessels. Collectively, it appears unlikely that the predisposition to PAH or intrapulmonary angiogenic environment contributes to the lesion development in broilers when compared with layers. It is suggested that the lesion development is associated with increased pulmonary arterial pressure, and that local EPC dysfunction may play a role in the process.

Expression variations of connective tissue growth factor in pulmonary arteries from smokers with and without chronic obstructive pulmonary disease

PubMed Central

Zhou, Si-jing; Li, Min; Zeng, Da-xiong; Zhu, Zhong-ming; Hu, Xian-Wei; Li, Yong-huai; Wang, Ran; Sun, Geng-yun

2015-01-01

Cigarette smoking contributes to the development of pulmonary hypertension (PH) complicated with chronic obstructive pulmonary disease (COPD), and the pulmonary vascular remodeling, the structural basis of PH, could be attributed to abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs).In this study, morphometrical analysis showed that the pulmonary vessel wall thickness in smoker group and COPD group was significantly greater than in nonsmokers. In addition, we determined the expression patterns of connective tissue growth factor (CTGF) and cyclin D1 in PASMCs harvested from smokers with normal lung function or mild to moderate COPD, finding that the expression levels of CTGF and cyclin D1 were significantly increased in smoker group and COPD group. In vitro experiment showed that the expression of CTGF, cyclin D1 and E2F were significantly increased in human PASMCs (HPASMCs) treated with 2% cigarette smoke extract (CSE), and two CTGF siRNAs with different mRNA hits successfully attenuated the upregulated cyclin D1 and E2F, and significantly restored the CSE-induced proliferation of HPASMCs by causing cell cycle arrest in G0. These findings suggest that CTGF may contribute to the pathogenesis of abnormal proliferation of HPASMCs by promoting the expression of its downstream effectors in smokers with or without COPD. PMID:25708588

Effect of Rho kinase inhibitor fasudil on the expression ET-1 and NO in rats with hypoxic pulmonary hypertension.

PubMed

Sun, Xing-Zhen; Li, Shu-Yan; Tian, Xiang-Yang; Hong, Ze; Li, Jia-Xin

2018-04-12

This study aims to study the effect of Rho kinase inhibitor fasudil on the expression endothelin-1 (ET-1) and nitric oxide (NO) in rats with hypoxic pulmonary hypertension (HPH). Twenty-four male SD rats were randomly divided into three groups: control group, model group (HPH group) and HPH+fasudil group. The rat HPH model was established by intermittent hypoxia (IH) at atmospheric pressure. Mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI), ET-1 and NO levels, and pulmonary vascular structural changes were observed in all groups. MPAP, RVHI and ET-1 levels were significantly higher in HPH group than in control group, while NO was significantly lower than in control group. In addition, mPAP, RVHI and ET-1 were significantly lower in the HPH+fasudil group than in the HPH group. In the HPH group, ET-1 level was significantly and positively correlated with mPAP and RVHI, NO was negatively correlated with mPAP and RVHI levels, and ET-1 level was significantly and negatively correlated with NO level. In the HPH group, pulmonary arteriolar walls were generally thickened, and lumen stenosis was obvious; while after fasudil treatment, pulmonary arteriolar wall thickening and stenosis degree were significantly reduced. Fasudil can significantly reduce ET-l level and increase NO level in HPH rats, suppressing the development of pulmonary arterial hypertension.

Effects and mechanism of oridonin on pulmonary hypertension induced by chronic hypoxia-hypercapnia in rats.

PubMed

Wang, Liang-Xing; Sun, Yu; Chen, Chan; Huang, Xiao-Ying; Lin, Quan; Qian, Guo-Qing; Dong, Wei; Chen, Yan-Fan

2009-06-20

Pulmonary arterial hypertension (PAH) is characterized by suppressing apoptosis and enhancing cell proliferation in the vascular wall. Inducing pulmonary artery smooth muscle cells (PASMC) apoptosis had been regarded as a therapeutic approach for PAH. Oridonin can cause apoptosis in many cell lines, while little has been done to evaluate its effect on PASMC. Thirty male Sprague-Dawley rats were randomly assigned to three groups: normal control (NC); hypoxia-hypercapnia (HH); Hypoxia-hypercapnia + oridonin (HHO). Rats were exposed to hypoxia-hypercapnia for four weeks. Cultured human PASMC (HPASMC) were assigned to three groups: normoxia (NO); hypoxia (HY); hypoxia + oridonin (HO). The mean pulmonary artery pressure, mass ratio of right ventricle over left ventricle plus septum (RV/(LV + S)), the ratio of thickness of the pulmonary arteriole wall to vascular external diameter (WT%) and the ratio of the vessel wall area to the total area (WA%) were measured. Morphologic changes of pulmonary arteries were observed under light and electron microscopes. The apoptotic characteristics in vitro and in vivo were detected. The mPAP, RV/(LV + S), WT%, and WA% in the HH group were significantly greater than those in the NC (P < 0.01) and HHO groups (P < 0.01); the activities of caspase-3 and caspase-9, and the expressions of Bax, cyt-C and apoptotic index (AI) in the group HH were less than those in the NC and HHO groups; and the expression of Bcl-2 in group HH was greater than that in the NC and HHO groups. HPASMC mitochondrial membrane potentials in group HO was lower than in group HY (P < 0.01), and cyt-C in the cytoplasm, AI, and caspase-9 in the HO group were greater than that in the HY group (P < 0.01), but the expression of Bcl-2 in the HO group was less than that in the HY group (P < 0.05). The results suggest that oridonin can lower pulmonary artery pressure effectively, and inhibit pulmonary artery structural remodeling by inducing smooth cell apoptosis via a mitochondria-dependent pathway.

Rare Anomalous Origin of Superior Left Pulmonary Artery from Left Subclavian Vein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lv, Tian-shi, E-mail: TerrenceLv@126.com; Wang, Chao, E-mail: wangchaoxs@163.com; Song, Li, E-mail: song9981@163.com

2013-10-15

We report for the first time an extremely rare anomalous origin of the superior left pulmonary artery in a 60 year-old man. Although it was occult in clinical indications, such a malformation still ought to be considered, especially during endovascular procedures.

The importance of preoperative oxygen saturation as a predictor of pulmonary arterial hypertension after surgery of atrial septal defects.

PubMed

Park, Han Ki; Shin, Hong Ju; Park, Young Hwan; Ma, Bo Gyoung

2016-09-01

There is no concrete predictor of the change of pulmonary arterial pressure after surgical closure of an atrial septal defect (ASD) in patients with pulmonary arterial hypertension (PAH). The aim of this study was to investigate the role of preoperative room air arterial oxygen saturation (SaO2) (arterial blood gas data) as a predictor of postoperative PAH. The medical records of 36 patients [>20 years, mean pulmonary arterial pressure (mPAP) ≥25 mmHg] who underwent surgical closure of an ASD between March 2004 and January 2014 were retrospectively reviewed. The median age was 47 years (range, 24.6-65.9 years) and mPAP was 38 ± 14 mmHg. The mean pulmonary vascular resistance (Rp) was 3.9 ± 4.2 Wood units, and fenestration was performed in 12 (33%) patients. Only 1 patient received anti-PAH medication preoperatively. The median follow-up period was 4 years (range, 0-10 years). There were two hospital deaths, one of which was related to PAH. At the last follow-up, PAH (estimated tricuspid regurgitation velocity >3 m/s) existed in 7 patients (19%), and 10 patients (28%) were receiving anti-PAH medications (considered as clinical PAH). Univariate analysis for persistent clinical PAH revealed that mPAP, Qp/Qs, Rp, room air arterial oxygen saturation and postoperative functional class were significant risk factors. Only SaO2 remained a significant risk factor in multivariate analysis (P = 0.03). Preoperative room air SaO2 is a useful predictor of persistent PAH in adult patients undergoing surgical closure of an ASD. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

[Transcatheter embolization for huge pulmonary arteriovenous fistula using metallic "spider" and spring embolus--application of hand-made metallic "spider" using partial monorail technique].

PubMed

Hirota, S; Sako, M; Fujita, Y; Hasegawa, Y; Sugimoto, K; Suzuki, Y; Kono, M

1992-07-25

We performed transcatheter embolization in two cases with huge pulmonary arteriovenous fistula (AVF) using a metallic "spider" and spring embolus. Conventional spring embolus or detachable balloon could not be used in these cases. Metallic spider was indicated for pulmonary AVF with a feeding artery diameter of more than 16 mm to prevent embolus passing through the AVF. In the first case, we used large handmade metallic spiders of 25 mm in diameter followed by embolization by numerous spring coils. At that time, a partial monorail technique was newly devised to carry the large metallic spider into the feeding artery, otherwise the spider could not pass into a 9F catheter. After embolization, symptoms and PaO2 in arterial blood improved remarkably in both cases. In the second case, a spring coil migrated into the normal pulmonary artery, but no infarction resulted. In conclusion, the metallic spider was very useful for embolization of hugee pulmonary AVF to avoid the embolus passing through and to tangle spring coils together with it. If commercially available "spiders" are too small, ones can be made easily.

Endobronchial ultrasound-guided transbronchial needle aspiration of pulmonary artery tumors: A systematic review (with video).

PubMed

Harris, Kassem; Modi, Kush; Kumar, Abhishek; Dhillon, Samjot Singh

2015-01-01

Convex probe endobronchial ultrasound (CP-EBUS) was originally introduced as a diagnostic and staging tool for lung cancer and subsequently utilized for diagnosis of other malignant and benign mediastinal diseases such as melanoma, lymphoma, and sarcoidosis. More recently, CP-EBUS has been successfully used for the visualization and diagnosis of pulmonary emboli and other vascular lesions including primary and metastatic pulmonary artery (PA) tumors. In this review, we will underline the role of EBUS-guided transbronchial needle aspiration (EBUS-TBNA) for the diagnosis of pulmonary arterial tumors such as sarcomas and tumor emboli. We will concisely discuss the clinical applications of EBUS-TBNA and the types of pulmonary arterial tumors and their different diagnostic modalities. We searched the Cochrane Library and PubMed from 2004 to 2014 to provide the most comprehensive review. Only 10 cases of EBUS-TBNA for intravascular lesions were identified in the literature. Although many cases of EBUS and EUS-guided transvascular tumor biopsies were described in the literature, there were no reported cases of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for intravascular tumor biopsies. Except for one paper, all cases were published as case reports.

Injury Pattern and Mortality of Noncompressible Torso Hemorrhage in UK Combat Casualties

DTIC Science & Technology

2013-08-01

body disruption (5.1%), and multiple-organ failure (4.0%). On multivariate analysis, major arterial and pulmonary hilar injury are most lethal with odds...death. Major arterial and pulmonary hilar injuries are independent predictors of mortality. (J Trauma Acute Care Surg. 2013;75: S263YS268. Copyright...physiologic or procedural indices of shock.8 Anatomic refers to those injuries to a named torso vessel, pulmonary injury (massive hemothorax or hilar

Computational Fluid Dynamics Modeling of the Human Pulmonary Arteries with Experimental Validation.

PubMed

Bordones, Alifer D; Leroux, Matthew; Kheyfets, Vitaly O; Wu, Yu-An; Chen, Chia-Yuan; Finol, Ender A

2018-05-21

Pulmonary hypertension (PH) is a chronic progressive disease characterized by elevated pulmonary arterial pressure, caused by an increase in pulmonary arterial impedance. Computational fluid dynamics (CFD) can be used to identify metrics representative of the stage of PH disease. However, experimental validation of CFD models is often not pursued due to the geometric complexity of the model or uncertainties in the reproduction of the required flow conditions. The goal of this work is to validate experimentally a CFD model of a pulmonary artery phantom using a particle image velocimetry (PIV) technique. Rapid prototyping was used for the construction of the patient-specific pulmonary geometry, derived from chest computed tomography angiography images. CFD simulations were performed with the pulmonary model with a Reynolds number matching those of the experiments. Flow rates, the velocity field, and shear stress distributions obtained with the CFD simulations were compared to their counterparts from the PIV flow visualization experiments. Computationally predicted flow rates were within 1% of the experimental measurements for three of the four branches of the CFD model. The mean velocities in four transversal planes of study were within 5.9 to 13.1% of the experimental mean velocities. Shear stresses were qualitatively similar between the two methods with some discrepancies in the regions of high velocity gradients. The fluid flow differences between the CFD model and the PIV phantom are attributed to experimental inaccuracies and the relative compliance of the phantom. This comparative analysis yielded valuable information on the accuracy of CFD predicted hemodynamics in pulmonary circulation models.

Smooth Muscle-Mediated Connective Tissue Remodeling in Pulmonary Hypertension

NASA Astrophysics Data System (ADS)

Mecham, Robert P.; Whitehouse, Loren A.; Wrenn, David S.; Parks, William C.; Griffin, Gail L.; Senior, Robert M.; Crouch, Edmond C.; Stenmark, Kurt R.; Voelkel, Norbert F.

1987-07-01

Abnormal accumulation of connective tissue in blood vessels contributes to alterations in vascular physiology associated with disease states such as hypertension and atherosclerosis. Elastin synthesis was studied in blood vessels from newborn calves with severe pulmonary hypertension induced by alveolar hypoxia in order to investigate the cellular stimuli that elicit changes in pulmonary arterial connective tissue production. A two- to fourfold increase in elastin production was observed in pulmonary artery tissue and medial smooth muscle cells from hypertensive calves. This stimulation of elastin production was accompanied by a corresponding increase in elastin messenger RNA consistent with regulation at the transcriptional level. Conditioned serum harvested from cultures of pulmonary artery smooth muscle cells isolated from hypertensive animals contained one or more low molecular weight elastogenic factors that stimulated the production of elastin in both fibroblasts and smooth muscle cells and altered the chemotactic responsiveness of fibroblasts to elastin peptides. These results suggest that connective tissue changes in the pulmonary vasculature in response to pulmonary hypertension are orchestrated by the medial smooth muscle cell through the generation of specific differentiation factors that alter both the secretory phenotype and responsive properties of surrounding cells.

Rest and exercise echocardiography for early detection of pulmonary hypertension.

PubMed

Kusunose, Kenya; Yamada, Hirotsugu

2016-03-01

Early detection of pulmonary hypertension (PH) is essential to ensure that patients receive timely and appropriate treatment for this progressive disease. Rest and exercise echocardiography has been used to screen patients in an attempt to identify early stage PH. However, current PH guidelines recommend against exercise tests because of the lack of evidence. We reviewed previous studies to discuss the current standpoint concerning rest and exercise echocardiography in PH. Around 20 exercise echocardiography studies were included to assess the cutoff value for exercise-induced pulmonary hypertension (EIPH). Approximately 40 exercise echocardiography studies were also included to evaluate the pulmonary artery pressure-flow relationship as assessed by the slope of the mean pulmonary artery pressure and cardiac output (ΔmPAP/ΔQ). There were several EIPH and ΔmPAP/ΔQ reference values in individuals with pulmonary vascular disease. We believed that assessing the ΔmPAP/ΔQ makes sense from a physiological standpoint, and the clinical value should be confirmed in future studies. Exercise echocardiography is an appealing alternative in PH. Further studies are needed to assess the prognostic value of the pulmonary artery pressure-flow relationship in high-risk subjects.

[Pregnancy in pulmonary arterial hypertension patients].

PubMed

Rosengarten, Dror; Kramer, Mordechai R

2013-09-01

Pulmonary arterial hypertension (PAH) is a disorder defined by elevated mean pulmonary arterial pressure. PAH can be idiopathic or associated with a variety of medical conditions such as scleroderma, congenital heart disease, left heart failure, lung disease or chronic pulmonary thromboembolism. This progressive disease can cause severe right heart failure and death. Normal physiologic changes that occur during pregnancy may produce fatal consequences in PAH patients. Current guidelines recommend that pregnancy be avoided or terminated early in women with PAH. During the past decade, new advanced therapies for PAH have emerged gathering reports of successful pregnancies in patients with pulmonary hypertension. Substantial risk still exists and current recommendations have not changed. Nevertheless, in selected cases, if a patient insists on continuing the pregnancy, being fully aware of the risks involved, an intensive treatment approach should be implemented in experienced centers. This is necessary in order to control pulmonary hypertension during pregnancy and reduce the risk so as to improve outcomes. This review will focus on the pathophysiology of PAH in pregnancy and appropriate management during pregnancy, delivery and the post-partum period.

Osthole relaxes pulmonary arteries through endothelial phosphatidylinositol 3-kinase/Akt-eNOS-NO signaling pathway in rats.

PubMed

Yao, Li; Lu, Ping; Li, Yumei; Yang, Lijing; Feng, Hongxuan; Huang, Yong; Zhang, Dandan; Chen, Jianguo; Zhu, Daling

2013-01-15

Pulmonary arterial hypertension is a life-threatening disease lacking effective therapies. Osthole is a natural coumarin compound isolated from Angelica pubescens Maxim., which possesses hypotensive effect. Although its effects on isolated thoracic aorta (systemic circulating system) are clarified, it remains unclear whether Osthole relaxes isolated pulmonary arteries (PAs) (pulmonary circulating system). The aim of this study was to investigate the effects of Osthole on isolated PAs and the underlying mechanisms. We examined PA relaxation induced by Osthole in isolated human and rat PA rings with force-electricity transducers, the expression and activity of endothelial nitric oxide synthase (eNOS) and protein kinase B (Akt) with western blot, and nitric oxide (NO) production using DAF-FM DA fluorescent indicator. The results showed that Osthole elicited a dose-dependent vasorelaxation activity with phenylephrine-precontracted human and rat PA rings, which can be diminished by endothelium denudation and inhibition of eNOS, while having no effect on rat mesenteric arteries. Osthole increased NO release as well as activation of Akt and eNOS, indicated with increased phosphorylations of Akt at Ser-473 and eNOS at Ser-1177 in endothelial cells. PI3K inhibitor LY294002 also blocked Osthole induced vasodilation. In summary, dilative effect of Osthole was dependent on endothelial integrity and NO production, and was mediated by endothelial PI3K/Akt-eNOS-NO pathway. These may provide a new pulmonary vasodilator for the therapy of pulmonary arterial hypertension. Copyright © 2012 Elsevier B.V. All rights reserved.

'End-stage' heart failure therapy: potential lessons from congenital heart disease: from pulmonary artery banding and interatrial communication to parallel circulation.

PubMed

Schranz, Dietmar; Akintuerk, Hakan; Voelkel, Norbert F

2017-02-15

The final therapy of 'end-stage heart failure' is orthotopic heart, lung or heart-lung transplantation. However, these options are not available for many patients worldwide. Therefore, novel therapeutical strategies are needed. Based on pathophysiological insights regarding (1) the long-term impact of an obstructive pulmonary outflow tract in neonates with congenitally corrected transposition of the great arteries, (2) the importance of a restrictive versus a non-restrictive atrial septum in neonates born with a borderline left ventricle and (3) the significance of both, a patent foramen ovale and/or open ductus arteriosus for survival of newborns with persistent pulmonary hypertension, the current review introduces some therapeutical strategies that may be applicable to selected patients with heart failure. These strategies include (1) reversible pulmonary artery banding in left ventricular-dilated cardiomyopathy with preserved right ventricular function, (2) the creation of restrictive interatrial communication to treat diastolic (systolic) heart failure, (3) atrioseptostomy or reverse Potts shunt in pulmonary arterial hypertension and (4) return to a fetal, parallel circulation by combining atrioseptostomy and reversed Potts shunt with or without placement of a bilateral pulmonary artery banding. While still being experimental, it is hoped that the procedures presented in the current overview will inspire future novel therapeutic strategies that may be applicable to selected patients with heart failure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Estimating the effect of lung collapse and pulmonary shunt on gas exchange during breath-hold diving: the Scholander and Kooyman legacy.

PubMed

Fahlman, A; Hooker, S K; Olszowka, A; Bostrom, B L; Jones, D R

2009-01-01

We developed a mathematical model to investigate the effect of lung compression and collapse (pulmonary shunt) on the uptake and removal of O(2), CO(2) and N(2) in blood and tissue of breath-hold diving mammals. We investigated the consequences of pressure (diving depth) and respiratory volume on pulmonary shunt and gas exchange as pressure compressed the alveoli. The model showed good agreement with previous studies of measured arterial O(2) tensions (Pa(O)(2)) from freely diving Weddell seals and measured arterial and venous N(2) tensions from captive elephant seals compressed in a hyperbaric chamber. Pulmonary compression resulted in a rapid spike in Pa(O)(2) and arterial CO(2) tension, followed by cyclical variation with a periodicity determined by Q(tot). The model showed that changes in diving lung volume are an efficient behavioural means to adjust the extent of gas exchange with depth. Differing models of lung compression and collapse depth caused major differences in blood and tissue N(2) estimates. Our integrated modelling approach contradicted predictions from simple models, and emphasised the complex nature of physiological interactions between circulation, lung compression and gas exchange. Overall, our work suggests the need for caution in interpretation of previous model results based on assumed collapse depths and all-or-nothing lung collapse models.

Pulmonary arterial hypertension

PubMed Central

2013-01-01

Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role, essentially in the screening proposing criteria for estimating the presence of PH mainly based on tricuspid regurgitation peak velocity and systolic artery pressure (sPAP). The therapy of PAH consists of non-specific drugs including oral anticoagulation and diuretics as well as PAH specific therapy. Diuretics are one of the most important treatment in the setting of PH because right heart failure leads to fluid retention, hepatic congestion, ascites and peripheral edema. Current recommendations propose oral anticoagulation aiming for targeting an International Normalized Ratio (INR) between 1.5-2.5. Target INR for patients displaying chronic thromboembolic PH is between 2–3. Better understanding in pathophysiological mechanisms of PH over the past quarter of a century has led to the development of medical therapeutics, even though no cure for PAH exists. Several specific therapeutic agents were developed for the medical management of PAH including prostanoids (epoprostenol, trepoprostenil, iloprost), endothelin receptor antagonists (bosentan, ambrisentan) and phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). This review discusses the current state of art regarding to epidemiologic aspects of PH, diagnostic approaches and the current classification of PH. In addition, currently available specific PAH therapy is discussed as well as future treatments. PMID:23829793

Pulmonary capillary pressure in pulmonary hypertension.

PubMed

Souza, Rogerio; Amato, Marcelo Britto Passos; Demarzo, Sergio Eduardo; Deheinzelin, Daniel; Barbas, Carmen Silvia Valente; Schettino, Guilherme Paula Pinto; Carvalho, Carlos Roberto Ribeiro

2005-04-01

Pulmonary capillary pressure (PCP), together with the time constants of the various vascular compartments, define the dynamics of the pulmonary vascular system. Our objective in the present study was to estimate PCPs and time constants of the vascular system in patients with idiopathic pulmonary arterial hypertension (IPAH), and compare them with these measures in patients with acute respiratory distress syndrome (ARDS). We conducted the study in two groups of patients with pulmonary hypertension: 12 patients with IPAH and 11 with ARDS. Four methods were used to estimate the PCP based on monoexponential and biexponential fitting of pulmonary artery pressure decay curves. PCPs in the IPAH group were considerably greater than those in the ARDS group. The PCPs measured using the four methods also differed significantly, suggesting that each method measures the pressure at a different site in the pulmonary circulation. The time constant for the slow component of the biexponential fit in the IPAH group was significantly longer than that in the ARDS group. The PCP in IPAH patients is greater than normal but methodological limitations related to the occlusion technique may limit interpretation of these data in isolation. Different disease processes may result in different times for arterial emptying, with resulting implications for the methods available for estimating PCP.

Surgical repair and postoperative course of an infant with infracardiac total anomalous pulmonary venous connection, cor triatriatum sinistrum and transposition of the great arteries.

PubMed

Thies, W R; Matthies, W; Minami, K; Pott, U; Meyer, H; Körfer, R

1990-01-01

The combination of a d-transposition of the great arteries, cor triatriatum sinistrum and a total anomalous pulmonary venous connection of the infracardiac type is a very rare condition. Up to now, one surgical repair in an adolescent with transposed great arteries and total anomalous pulmonary venous drainage of the supracardiac type has been reported. In this paper, an infant with the above mentioned cardiovascular malformation is presented. The common pulmonary vein drained into the inferior vena cava and was obstructed. There were arborisation abnormalities in both lungs with mild pulmonary hypertension. The infant has been successfully operated upon at the age of 6 months and a weight of 4.5 kg. The membrane within the left atrium was resected, the common pulmonary vein was anastomosed to the left atrium and a Mustard procedure was performed. During the first 6 postoperative weeks, the infant had problems with adaptation. There was both a transient ballooning of the Mustard patch with significant obstruction of the pulmonary venous drainage and a delayed pulmonary recovery. Two months later, the patch was straightened and the child could be discharged from hospital. After 12 months, the child died from an infection of the airways.

Robust extraction of the aorta and pulmonary artery from 3D MDCT image data

NASA Astrophysics Data System (ADS)

Taeprasartsit, Pinyo; Higgins, William E.

2010-03-01

Accurate definition of the aorta and pulmonary artery from three-dimensional (3D) multi-detector CT (MDCT) images is important for pulmonary applications. This work presents robust methods for defining the aorta and pulmonary artery in the central chest. The methods work on both contrast enhanced and no-contrast 3D MDCT image data. The automatic methods use a common approach employing model fitting and selection and adaptive refinement. During the occasional event that more precise vascular extraction is desired or the method fails, we also have an alternate semi-automatic fail-safe method. The semi-automatic method extracts the vasculature by extending the medial axes into a user-guided direction. A ground-truth study over a series of 40 human 3D MDCT images demonstrates the efficacy, accuracy, robustness, and efficiency of the methods.

Pulmonary artery dissection following balloon valvuloplasty in a dog with pulmonic stenosis.

PubMed

Grint, K A; Kellihan, H B

2017-04-01

A 3-month-old, 9.9 kg, male pit bull cross was referred for evaluation of collapse. A left basilar systolic heart murmur graded V/VI and a grade IV/VI right basilar systolic heart murmur were ausculted. Echocardiography showed severe pulmonic stenosis characterized by annular hypoplasia, leaflet thickening, and leaflet fusion. After 1 month of atenolol therapy, a pulmonic valve balloon valvuloplasty procedure was performed, and the intra-operative right ventricular pressure was reduced by 43%. Echocardiography, performed the following day, showed apparent rupture of a pulmonary valve leaflet and a membranous structure within the pulmonary artery consistent with a dissecting membrane. Short-term follow-up has shown no apparent progression of the pulmonary artery dissection and the patient remains free of clinical signs. Copyright © 2016 Elsevier B.V. All rights reserved.

[Horseshoe lung with normal pulmonary venous return].

PubMed

Gondra Sangroniz, A; Elorz Lambarri, J; Villar Alvarez, M A; Lecumberri Cortes, I; Ayala Curiel, J

2010-09-01

Horseshoe lung is a rare congenital anomaly characterised by a midline isthmus of pulmonary parenchyma connecting the posterior basal segments of the lungs behind the heart in conjunction with unilateral pulmonary hypoplasia. Of all cases, 80% are associated with scimitar syndrome, consisting of right anomalous pulmonary venous drainage, pulmonary hypoplasia of the right lung and systemic arterial perfusion to some lung areas. A six year old girl who had recurrent lower respiratory infections since birth. Chest Rx, angioCT and MR showed: hypoplasia of the right lung, dextrocardia and pulmonary isthmus bridging both lungs behind the pericardium. The right hypoplastic lung had little systemic supply coming from the abdominal aorta. The right pulmonary artery was hypoplastic. The right pulmonary venous drainage was normal. We present a case of horseshoe lung without abnormal venous drainage. 2010 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Management of pulmonary arterial hypertension.

PubMed

McLaughlin, Vallerie V; Shah, Sanjiv J; Souza, Rogerio; Humbert, Marc

2015-05-12

Pulmonary hypertension (PH) is common and may result from a number of disorders, including left heart disease, lung disease, and chronic thromboembolic disease. Pulmonary arterial hypertension (PAH) is an uncommon disease characterized by progressive remodeling of the distal pulmonary arteries, resulting in elevated pulmonary vascular resistance and, eventually, in right ventricular failure. Over the past decades, knowledge of the basic pathobiology of PAH and its natural history, prognostic indicators, and therapeutic options has exploded. A thorough evaluation of a patient is critical to correctly characterize the PH. Cardiac studies, including echocardiography and right heart catheterization, are key elements in the assessment. Given the multitude of treatment options currently available for PAH, assessment of risk and response to therapy is critical in long-term management. This review also underscores unique situations, including perioperative management, intensive care unit management, and pregnancy, and highlights the importance of collaborative care of the PAH patient through a multidisciplinary approach. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Lung salvage by pulmonary arterioplasty after vascular injury during video-assisted thoracoscopic surgical right upper lobectomy.

PubMed

Petel, M R; Mahieu, J; Baste, J M

2015-01-01

Video Assisted Thoracoscopic Surgical (VATS) lobectomy is now considered feasible and safe. Nevertheless, thoracic surgeons need to be aware of dramatic complications that may occur during this procedure and how best to manage them. We report the case of a severe tear of the right pulmonary artery (PA) during elective VATS upper lobectomy, leading to emergency conversion to control the bleeding. Initial arterial repair was performed by end-to-end anastomosis. Early CT angiography showed thrombosis of the right PA due to anastomotic stenosis. We performed emergency pulmonary arterioplasty with a prosthetic patch to save the right lung. A CT scan days after surgical lung salvage confirmed the permeability of the PA and normal vascularization of the two remaining right lobes. We discuss herein this dramatic complication of VATS lobectomy, the viability of the lung after pulmonary arterial thrombosis, and advocate for early postoperative imaging after pulmonary arterioplasty. Copyright© Acta Chirurgica Belgica.

Successful Treatment of Suspected Pulmonary Arterial Hypertension in a Mealy Amazon Parrot (Amazona farinose).

PubMed

Brady, Sean M; Burgdorf-Moisuk, Anne; Silverman, Sarah; Wack, Raymund F

2016-12-01

A 25-year-old, male mealy Amazon parrot (Amazona farinose) with a history of polycythemia, hepatomegaly, and epistaxis was evaluated for progressive lethargy and anorexia. Clinical laboratory testing revealed severe polycythemia (71%), hypophosphatemia (1.6 mg/dL), and mild hypokalemia (2.8 mEq/L). Radiographs showed marked hepatomegaly and loss of air sac space. Despite supportive treatments, the bird's condition deteriorated, and it developed ataxia, was unable to fly, and became oxygen dependent. An echocardiogram, including an air bubble study, revealed a right-to-left atrial shunt and presumed pulmonary arterial hypertension. The bird was started on periodic phlebotomy (5-10 mL/kg q6wk) to reduce packed cell volume and sildenafil citrate (2.5 mg/kg PO q8h) for treatment of suspected pulmonary arterial hypertension. One week later, the patient was weaned off oxygen, and 24 days after initial presentation, the parrot was returned to its outdoor exhibit. Intermittent periods of increased respiratory rate and effort have been reported but have resolved without additional treatments. Epistaxis, once common in this bird, has not been noted since initiating treatment with sildenafil citrate 15 months ago.

Novel Approaches to Pulmonary Arterial Hypertension Drug Discovery

PubMed Central

Sung, Yon K.; Yuan, Ke; de Jesus Perez, Vinicio A.

2016-01-01

Introduction Pulmonary arterial hypertension (PAH) is a rare disorder associated with abnormally elevated pulmonary pressures that, if untreated, leads to right heart failure and premature death. The goal of drug development for PAH is to develop effective therapies that halt, or ideally, reverse the obliterative vasculopathy that results in vessel loss and obstruction of blood flow to the lungs. Areas Covered This review summarizes the current approach to candidate discovery in PAH and discusses the currently available drug discovery methods that should be implemented to prioritize targets and obtain a comprehensive pharmacological profile of promising compounds with well-defined mechanisms. Expert opinion To improve the successful identification of leading drug candidates, it is necessary that traditional pre-clinical studies are combined with drug screening strategies that maximize the characterization of biological activity and identify relevant off-target effects that could hinder the clinical efficacy of the compound when tested in human subjects. A successful drug discovery strategy in PAH will require collaboration of clinician scientists with medicinal chemists and pharmacologists who can identify compounds with an adequate safety profile and biological activity against relevant disease mechanisms. PMID:26901465

Successful two-stage correction of ventricular septal defect and patent ductus arteriosus in a patient with fixed pulmonary hypertension.

PubMed

Pac, Aysenur; Polat, Tugcin Bora; Vural, Kerem; Pac, Mustafa

2010-01-01

We report a case of a 6-year-old boy with fixed severe pulmonary artery hypertension secondary to a ventricular septal defect (VSD) together with a patent ductus arteriosus (PDA). As a preliminary step, PDA embolization was performed following therapy with inhaled prostacyclin over a period of 6 months. Further, the patient underwent successful surgical VSD closure. We postulate that a staged procedure with long-term prostaglandin therapy might be capable of reducing pulmonary artery resistance and permitting total correction in a patient once considered to have inoperable pulmonary arteriopathy.

Echocardiographic Assessment of Pulmonary Arterial Hypertension for Pediatricians and Neonatologists.

PubMed

Skinner, Gregory James

2017-01-01

There is a growing awareness of the role that increased pulmonary vascular resistance (PVR) plays in many pathologies; therefore, assessment of pulmonary artery pressure (PAP) is an increasingly requested investigation in the critical care environment. This article will go through the basic concepts regarding PAP and PVR, then will go on to outline the various echocardiographic parameters which are used to assess them. Finally, an outline of how to undertake this assessment will be presented.

Left atrium and pulmonary artery compression due to aortic aneurysm causing heart failure symptoms.

PubMed

Jorge, Antonio José Lagoeiro; Martins, Wolney de Andrade; Moutinho, Victor M; Rezende, Juliano M; Alves, Patricia Y; Villacorta, Humberto; Silveira, Pedro F; Couto, Antonio A

2018-06-01

Patients with thoracic aortic aneurysm (TAA) are mostly asymptomatic and TAA is rarely related to heart failure (HF). We report the case of an 80-year-old female patient, with type A TAA without dissection, with right pulmonary artery and left atrium compression, who presented with HF, preserved ejection fraction and acute pulmonary edema. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Right Cardiac Chambers Involvement by a Malignant Testicular Germ Cell Tumor: An Imaging-pathologic Correlation.

PubMed

do Nascimento, Felipe Barjud Pereira; Albieri, Lilian; Bento Dos Santos, Glaucia Aparecida; Dolhnikoff, Marisa

2016-07-01

The cardiac chamber's involvement with neoplastic embolism has been rarely reported; it is mostly associated with gastric, breast, lung, liver, and prostate cancers, and usually affects the pulmonary arteries. This paper reports a case of a 31-year-old man with a malignant testicular germ cell tumor who presented with multiple episodes of pulmonary thromboembolism and died of sudden respiratory failure 1 year after the initial diagnosis. Death was attributed to massive pulmonary embolism and pulmonary infarction associated with a neoplastic thrombus that extended from the gonadal veins to pulmonary arteries. A postmortem computerized tomographic angiography and autopsy confirmed this finding. Copyright © 2016 Elsevier Inc. All rights reserved.

Radiographic findings in pulmonary hypertension from unresolved embolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woodruff, W.W. III; Hoeck, B.E.; Chitwood, W.R. Jr.

1985-04-01

Pulmonary artery hypertension with chronic pulmonary embolism is an uncommon entity that is potentially treatable with pulmonary embolectomy. Although the classic radiographic features have been described, several recent investigators report a significant percentage of these patients with normal chest radiographs. In a series of 22 patients, no normal radiographs were seen. Findings included cardiomegaly (86.4%) with right-sided enlargement (68.4%), right descending pulmonary artery enlargement (54.5%), azygos vein enlargement (27.3%), mosaic oligemia (68.2%), chronic volume loss (27.3%), atelectasis and/or effusion (22.7%), and pleural thickening (13.6%). Good correlation with specific areas of diminished vascularity was seen on chest radiographs compared with pulmonarymore » angiograms.« less

Reduction of lymph tissue false positives in pulmonary embolism detection

NASA Astrophysics Data System (ADS)

Ghanem, Bernard; Liang, Jianming; Bi, Jinbo; Salganicoff, Marcos; Krishnan, Arun

2008-03-01

Pulmonary embolism (PE) is a serious medical condition, characterized by the partial/complete blockage of an artery within the lungs. We have previously developed a fast yet effective approach for computer aided detection of PE in computed topographic pulmonary angiography (CTPA),1 which is capable of detecting both acute and chronic PEs, achieving a benchmark performance of 78% sensitivity at 4 false positives (FPs) per volume. By reviewing the FPs generated by this system, we found the most dominant type of FP, roughly one third of all FPs, to be lymph/connective tissue. In this paper, we propose a novel approach that specifically aims at reducing this FP type. Our idea is to explicitly exploit the anatomical context configuration of PE and lymph tissue in the lungs: a lymph FP connects to the airway and is located outside the artery, while a true PE should not connect to the airway and must be inside the artery. To realize this idea, given a detected candidate (i.e. a cluster of suspicious voxels), we compute a set of contextual features, including its distance to the airway based on local distance transform and its relative position to the artery based on fast tensor voting and Hessian "vesselness" scores. Our tests on unseen cases show that these features can reduce the lymph FPs by 59%, while improving the overall sensitivity by 3.4%.

Pulmonary Catherization Data Correlate Poorly with Renal Function in Heart Failure.

PubMed

Masha, Luke; Stone, James; Stone, Danielle; Zhang, Jun; Sheng, Luo

2018-04-10

The mechanisms of renal dysfunction in heart failure are poorly understood. We chose to explore the relationship of cardiac filling pressures and cardiac index (CI) in relation to renal dysfunction in advanced heart failure. To determine the relationship between renal function and cardiac filling pressures using the United Network of Organ Sharing (UNOS) pulmonary artery catherization registry. Patients over the age of 18 years who were listed for single-organ heart transplantation were included. Exclusion criteria included a history of mechanical circulatory support, previous transplantation, any use of renal replacement therapy, prior history of malignancy, and cardiac surgery, amongst others. Correlations between serum creatinine (SCr) and CI, pulmonary capillary wedge pressure (PCWP), pulmonary artery systolic pressure (PASP), and pulmonary artery diastolic pressure (PADP) were assessed by Pearson correlation coefficients and simple linear regression coefficients. Pearson correlation coefficients between SCr and PCWP, PASP, and PADP were near zero with values of 0.1, 0.07, and 0.08, respectively (p < 0.0001). A weak negative correlation coefficient between SCr and CI was found (correlation coefficient, -0.045, p = 0.027). In a subgroup of young patients unlikely to have noncardiac etiologies, no significant correlations between these values were identified. These findings suggest that, as assessed by pulmonary artery catherization, none of the factors - PCWP, PASP, PADP, or CI - play a prominent role in cardiorenal syndromes. © 2018 S. Karger AG, Basel.

Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia.

PubMed

Jiménez, Julio; Richter, Jute; Nagatomo, Taro; Salaets, Thomas; Quarck, Rozenn; Wagennar, Allard; Wang, Hongmei; Vanoirbeek, Jeroen; Deprest, Jan; Toelen, Jaan

2016-10-24

Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth. Pulmonary artery Doppler measurements, micro-CT barium angiograms and media thickness of peripheral pulmonary arteries were affected after seven days of hyperoxia when compared to controls. The parenchyma was also affected both at the functional and structural level. Lung function testing showed higher tissue resistance and elastance, with a decreased lung compliance and lung capacity. Histologically hyperoxia leads to fewer and larger alveoli with thicker walls, less developed distal airways and more inflammation than normoxia. In conclusion, we show that the rabbit model develops pulmonary hypertension and developmental lung arrest after preterm lung injury, which parallel the early changes in human BPD. Thus it enables the testing of pharmaceutical agents that target the cardiovascular compartment of the lung for further translation towards the clinic.

Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia

PubMed Central

Jiménez, Julio; Richter, Jute; Nagatomo, Taro; Salaets, Thomas; Quarck, Rozenn; Wagennar, Allard; Wang, Hongmei; Vanoirbeek, Jeroen; Deprest, Jan; Toelen, Jaan

2016-01-01

Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth. Pulmonary artery Doppler measurements, micro-CT barium angiograms and media thickness of peripheral pulmonary arteries were affected after seven days of hyperoxia when compared to controls. The parenchyma was also affected both at the functional and structural level. Lung function testing showed higher tissue resistance and elastance, with a decreased lung compliance and lung capacity. Histologically hyperoxia leads to fewer and larger alveoli with thicker walls, less developed distal airways and more inflammation than normoxia. In conclusion, we show that the rabbit model develops pulmonary hypertension and developmental lung arrest after preterm lung injury, which parallel the early changes in human BPD. Thus it enables the testing of pharmaceutical agents that target the cardiovascular compartment of the lung for further translation towards the clinic. PMID:27783043

MicroRNA-Dependent Control of Serotonin-Induced Pulmonary Arterial Contraction.

PubMed

Dahan, Diana; Hien, Tran Thi; Tannenberg, Philip; Ekman, Mari; Rippe, Catarina; Boettger, Thomas; Braun, Thomas; Tran-Lundmark, Karin; Tran, Phan-Kiet; Swärd, Karl; Albinsson, Sebastian

2017-01-01

Serotonin (5-HT) is considered to play a role in pulmonary arterial hypertension by regulating vascular remodeling and smooth muscle contractility. Here, arteries from mice with inducible and smooth muscle-specific deletion of Dicer were used to address mechanisms by which microRNAs control 5-HT-induced contraction. Mice were used 5 weeks after Dicer deletion, and pulmonary artery contractility was analyzed by wire myography. No change was seen in right ventricular systolic pressure following dicer deletion, but systemic blood pressure was reduced. Enhanced 5-HT-induced contraction in Dicer KO pulmonary arteries was associated with increased 5-HT2A receptor mRNA expression whereas 5-HT1B and 5-HT2B receptor mRNAs were unchanged. Contraction by the 5-HT2A agonist TCB-2 was increased in Dicer KO as was the response to the 5-HT2B agonist BW723C86. Effects of Src and protein kinase C inhibition were similar in control and KO arteries, but the effect of inhibition of Rho kinase was reduced. We identified miR-30c as a potential candidate for 5-HT2A receptor regulation as it repressed 5-HT2A mRNA and protein. Our findings show that 5-HT receptor signaling in the arterial wall is subject to regulation by microRNAs and that this entails altered 5-HT2A receptor expression and signaling. © 2017 S. Karger AG, Basel.

Pulmonary vasculature in COPD: The silent component.

PubMed

Blanco, Isabel; Piccari, Lucilla; Barberà, Joan Albert

2016-08-01

Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction that results from an inflammatory process affecting the airways and lung parenchyma. Despite major abnormalities taking place in bronchial and alveolar structures, changes in pulmonary vessels also represent an important component of the disease. Alterations in vessel structure are highly prevalent and abnormalities in their function impair gas exchange and may result in pulmonary hypertension (PH), an important complication of the disease associated with reduced survival and worse clinical course. The prevalence of PH is high in COPD, particularly in advanced stages, although it remains of mild to moderate severity in the majority of cases. Endothelial dysfunction, with imbalance between vasodilator/vasoconstrictive mediators, is a key determinant of changes taking place in pulmonary vasculature in COPD. Cigarette smoke products may perturb endothelial cells and play a critical role in initiating vascular changes. The concurrence of inflammation, hypoxia and emphysema further contributes to vascular damage and to the development of PH. The use of drugs that target endothelium-dependent signalling pathways, currently employed in pulmonary arterial hypertension, is discouraged in COPD due to the lack of efficacy observed in randomized clinical trials and because there is compelling evidence indicating that these drugs may worsen pulmonary gas exchange. The subgroup of patients with severe PH should be ideally managed in centres with expertise in both PH and chronic lung diseases because alterations of pulmonary vasculature might resemble those observed in pulmonary arterial hypertension. Because this condition entails poor prognosis, it warrants specialist treatment. © 2016 Asian Pacific Society of Respirology.

Predicting the Necessity for Extracorporeal Circulation During Lung Transplantation: A Feasibility Study.

PubMed

Hinske, Ludwig Christian; Hoechter, Dominik Johannes; Schröeer, Eva; Kneidinger, Nikolaus; Schramm, René; Preissler, Gerhard; Tomasi, Roland; Sisic, Alma; Frey, Lorenz; von Dossow, Vera; Scheiermann, Patrick

2017-06-01

The factors leading to the implementation of unplanned extracorporeal circulation during lung transplantation are poorly defined. Consequently, the authors aimed to identify patients at risk for unplanned extracorporeal circulation during lung transplantation. Retrospective data analysis. Single-center university hospital. A development data set of 170 consecutive patients and an independent validation cohort of 52 patients undergoing lung transplantation. The authors investigated a cohort of 170 consecutive patients undergoing single or sequential bilateral lung transplantation without a priori indication for extracorporeal circulation and evaluated the predictive capability of distinct preoperative and intraoperative variables by using automated model building techniques at three clinically relevant time points (preoperatively, after endotracheal intubation, and after establishing single-lung ventilation). Preoperative mean pulmonary arterial pressure was the strongest predictor for unplanned extracorporeal circulation. A logistic regression model based on preoperative mean pulmonary arterial pressure and lung allocation score achieved an area under the receiver operating characteristic curve of 0.85. Consequently, the authors developed a novel 3-point scoring system based on preoperative mean pulmonary arterial pressure and lung allocation score, which identified patients at risk for unplanned extracorporeal circulation and validated this score in an independent cohort of 52 patients undergoing lung transplantation. The authors showed that patients at risk for unplanned extracorporeal circulation during lung transplantation could be identified by their novel 3-point score. Copyright © 2017 Elsevier Inc. All rights reserved.