scholarly journals Application of A Microstructural Constitutive Model of the Pulmonary Artery to Patient-Specific Studies: Validation and Effect of Orthotropy

2006 ◽  
Vol 129 (2) ◽  
pp. 193-201 ◽  
Author(s):  
Yanhang Zhang ◽  
Martin L. Dunn ◽  
Kendall S. Hunter ◽  
Craig Lanning ◽  
D. Dunbar Ivy ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Animal Studies ◽  
Three Dimensional ◽  
Vascular Anatomy ◽  
Initial Study ◽  
Patient Specific ◽  
Pulmonary Vasculature ◽  
Cross Linking ◽  
Microstructural Model ◽  
Pulmonary Arterial

We applied a statistical mechanics based microstructural model of pulmonary artery mechanics, developed from our previous studies of rats with pulmonary arterial hypertension (PAH), to patient-specific clinical studies of children with PAH. Our previous animal studies provoked the hypothesis that increased cross-linking density of the molecular chains may be one biological remodeling mechanism by which the PA stiffens in PAH. This study appears to further confirm this hypothesis since varying molecular cross-linking density in the model allows us to simulate the changes in the P‐D loops between normotensive and hypertensive conditions reasonably well. The model was combined with patient-specific three-dimensional vascular anatomy to obtain detailed information on the topography of stresses and strains within the proximal branches of the pulmonary vasculature. The effect of orthotropy on stress∕strain within the main and branch PAs obtained from a patient was explored. This initial study also puts forward important questions that need to be considered before combining the microstructural model with complex patient-specific vascular geometries.

The pulmonary vasculature in a neonatal porcine model with increased pulmonary blood flow and pressure

2001 ◽  
Vol 11 (4) ◽  
pp. 420-430 ◽  
Author(s):  
Elisabeth V. Stenbøg ◽  
Daniel A. Steinbrüchel ◽  
Anne Bloch Thomsen ◽  
Ulrik Baandrup ◽  
Lene Heickendorff ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Artery ◽  
Vascular Disease ◽  
Pulmonary Blood Flow ◽  
Left Pulmonary Artery ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Systolic Pulmonary Arterial Pressure ◽  
Pulmonary Arterial ◽  
Circulating Levels

Introduction: Hypertension and hyperperfusion of the pulmonary vascular bed in the setting of congenital cardiac malformations may lead to progressive pulmonary vascular disease. To improve the understanding of the basic mechanisms of this disease, there is a need for clinically relevant animal models which reflect the disease process. Material and Results: We randomly allocated 45 newborn pigs, at the age of 48 hrs, to groups in which there was either construction of a 3 mm central aorto-pulmonary shunt, undertaken in 9, or ligation of the left pulmonary artery, achieved in 13. Controls included sham operations in 13, or no operations in 10 pigs. Follow-up was continued for three months. The interventions were compatible with survival in most pigs. The shunts resulted in an acute 85% increase in systolic pulmonary arterial pressure, and a more than twofold increase in pulmonary blood flow. By three months of age, nearly all shunts had closed spontaneously, and haemodynamics were normal. Ligation of the left pulmonary artery resulted in a normal total pulmonary blood flow, despite only the right lung being perfused, and a 33% increase in systolic pulmonary arterial pressure. These haemodynamic changes were maintained throughout the period of study. In both groups, histomorphometry revealed markedly increased muscularity of the intra-acinar pulmonary arteries. Circulating levels of endothelin were normal in the shunted animals, and elevated in those with ligation of the left pulmonary artery. Conclusion: In neonatal porcine models of pulmonary vascular disease, created by construction of 3 mm central aorto-pulmonary shunts and ligation of one pulmonary artery, we observed histopathological changes of the pulmonary vasculature similar to early hypertensive pulmonary vascular disease in humans. Elevated circulating levels of endothelin were associated with abnormal haemodynamics rather than abnormal pathology. These findings could be valuable for future studies on the pathogenesis of hypertensive pulmonary vascular disease associated with congenital cardiac malformations.

Abstract 18587: Downregulation of Pulmonary Artery Endothelial Catechol-o-methyltransferase Activity by Aldosterone Increases Norepinephrine Levels in Pulmonary Arterial Hypertension

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Samantha Torquato ◽  
Kiyotake Ishikawa ◽  
Jaume Aguerro ◽  
Bradley A Maron ◽  
Joseph Loscalzo ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Right Heart Failure ◽  
Therapeutic Interventions ◽  
Pulmonary Vasculature ◽  
Methyltransferase Activity ◽  
Comt Activity ◽  
Pulmonary Arterial

Elevated levels of norepinephrine (NE) occur in pulmonary arterial hypertension (PAH) and are determined, in part, by the activity of catechol- O -methyltransferase (COMT). COMT degrades catecholamines, is negatively regulated by calcium, and is expressed by pulmonary artery endothelial cells (PAEC). As hyperaldosteronism occurs in PAH and aldosterone (ALDO) influences calcium levels, we hypothesized that ALDO decreases COMT activity to increase NE levels in PAH. Accordingly, human PAEC were treated with ALDO (10 -7 mol/L), a level that is achieved clinically in PAH, for up to 72 h. Compared to vehicle-treated PAEC, ALDO decreased COMT activity by 59.2 ± 6.2% (p<0.01) to increase NE levels in the medium (122.4 ± 11.8 vs. 210.7 ± 15.5 pg/mL/mg protein, p<0.01). This occurred as a result of an ALDO-mediated decrease in COMT protein expression by 52.6 ± 9.3% (p<0.01) as well as an increase in intracellular calcium levels (102.9 ± 21.0 vs. 167.7 ± 17.8 nmol/L, p<0.05) to inhibit activity. These effects were abrogated by coincubation with spironolactone. To determine the in vivo relevance of these findings, COMT was examined in the rat monocrotaline model of PAH with confirmed hyperALDO. COMT was decreased (47.6 ± 10.2 %control, p<0.05) in remodeled pulmonary arterioles with a concomitant increase in lung NE levels (432.8 ± 44.5 vs. 899.7 ± 34.2 pg/mL, p<0.01) compared to control rats. In the porcine pulmonary vein banding model of pulmonary hypertension (PH-pigs) with elevated mean pulmonary artery pressure (15[13-15] vs. 35[27-43], p<0.01) and pulmonary vascular resistance (PVR) index (1.97[1.74-2.28] vs. 5.78[2.61-8.75], p <0.05), ALDO levels were also increased (27.1 ± 5.1 vs. 60.8 ± 10.6 pg/mL, p<0.03) in advance of right heart failure as compared to sham controls. PH-pigs demonstrated a 48.3 ± 9.9% (p<0.02) decrease in pulmonary vascular COMT expression and an increase in NE levels (114.6 ± 20.2 vs. 1,622.6 ± 489.2 pg/mL, p<0.02) that correlated positively with ALDO levels (R 2 =0.58, p<0.02). These findings were confirmed in patients with PAH. Together, these data indicate that there is crosstalk in the pulmonary vasculature between ALDO and the sympathetic nervous system to regulate NE levels in PAH, and thus, have implications for therapeutic interventions.

scholarly journals Computational Fluid Dynamics Characterization of Two Patient-Specific Systemic-to-Pulmonary Shunts before and after Operation

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Neichuan Zhang ◽  
Haiyun Yuan ◽  
Xiangyu Chen ◽  
Jiawei Liu ◽  
Qifei Jian ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Pulmonary Artery ◽  
Energy Loss ◽  
Three Dimensional ◽  
Left Pulmonary Artery ◽  
Postoperative Recovery ◽  
Patient Specific ◽  
Wall Shear ◽  
Ct Data

Studying the haemodynamics of the central shunt (CS) and modified Blalock–Taussig shunt (MBTS) benefits the improvement of postoperative recovery for patients with an aorta-pulmonary shunt. Shunt configurations, including CS and MBTS, are virtually reconstructed for infants A and B based on preoperative CT data, and three-dimensional models of A, 11 months after CS, and B, 8 months after MBTS, are reconstructed based on postoperative CT data. A series of parameters including energy loss, wall shear stress, and shunt ratio are computed from simulation to analyse the haemodynamics of CS and MBTS. Our results showed that the shunt ratio of the CS is approximately 30% higher than the MBTS and velocity distribution in the left pulmonary artery (LPA) and right pulmonary artery (RPA) was closer to a natural development in the CS than the MBTS. However, energy loss of the MBTS is lower, and the MBTS can provide more symmetric pulmonary artery (PA) flow than the CS. With the growth of infants A and B, the shunt ratio of infants was decreased, but maximum wall shear stress and the distribution region of high wall shear stress (WSS) were increased, which raises the probability of thrombosis. For infant A, the preoperative abnormal PA structure directly resulted in asymmetric growth of PA after operation, and the LPA/RPA ratio decreased from 0.49 to 0.25. Insufficient reserved length of the MBTS led to traction phenomena with the growth of infant B; on the one hand, it increased the eddy current, and on the other hand, it increased the flow resistance of anastomosis, promoting asymmetric PA flow.

Understanding the Molecular Origins of Pulmonary Hypertension: Role of MicroRNAs

2012 ◽  
Vol 11 (3) ◽  
pp. 132-132
Author(s):  
Sebastien Bonnet
Keyword(s):  
Pulmonary Artery ◽  
Vascular Remodeling ◽  
Premature Death ◽  
Right Heart Failure ◽  
Pulmonary Vasculature ◽  
Inflammatory Processes ◽  
Pulmonary Arterial ◽  
Pulmonary Artery Smooth Muscle ◽  
Pulmonary Artery Endothelial Cell

Pulmonary arterial hypertension (PAH) is a disease of the pulmonary vasculature, defined by an elevated pulmonary vascular resistance, leading to right heart failure and premature death. The cause remains unknown and available treatments are limited. PAH is characterized by enhanced pulmonary artery smooth muscle cell (PASMC) and pulmonary artery endothelial cell (PAEC) proliferation and suppressed apoptosis within the pulmonary artery wall. It has been shown that this phenotype is associated with mitochondrial hyperpolarization and enhanced glycolysis over glucose oxidation (Warburg effect), which are sustained over time by the activation of the transcription factors HIF-1 and NFAT. Nonetheless, the mechanisms accounting for these abnormalities remain unknown. A common feature to all vascular remodeling processes is that in early stages of the disease, a significant increase in oxidative stress and inflammatory processes are observed, causing irreversible DNA damage and cell death.

Abstract 973: A Novel Anti-Inflammatory Therapeutic Approach for Pulmonary Arterial Hypertension: Blockade of NF-kB by Nano-DDS of NF-kB decoy to the lung ameliorates monocrotaline-induced PAH

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Satoshi Kimura ◽  
Kensuke Egashira ◽  
Chen Ling ◽  
Hiroyuki Tsujimoto ◽  
Kaori Hara ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Cross Sections ◽  
Animal Studies ◽  
Nuclear Factor Κb ◽  
Therapeutic Benefit ◽  
Pulmonary Vasculature ◽  
Pulmonary Arterial ◽  
Anti Inflammatory ◽  
Intratracheal Injection

Background: Inflammatory mechanisms are implicated in the pathogenesis of pulmonary arterial hypertension (PAH), and thus can be a promising therapeutic target of the devastating disease. Nuclear factor-κB (NF-κB) is a redox-sensitive transcription factor that controls expression of important inflammatory cytokines. However, no prior study addressed the role of NF-κB in PAH. We have developed nanotechnology-based drug delivery system (Nano-DDS) to the lung using intratracheal injection of bioabsorbable polymeric PLGA nanoparticle (NP, a mean diameter of 50 nm) for clinical application. Hypothesis: Blockade of NF-κB by Nano-DDS of NF-κB decoy to the lung ameliorates monocrotaline (MCT)-induced PAH. Methods and Results: [Immunohistochemical studies in human samples from autopsy] Immunohistochemical study using an antibody against activated form (α-p65) showed that activation of NF-κB was noted in the alveolar macrophage and pulmonary vasculature with medial hypertrophy from lung cross-sections from patients with severe PAH. These pathologic changes were associated with increased staining of IL-6 and MCP-1. [Experimental animal studies] Single intratracheal injection of NP incorporated with fluorescence labeled NF-κB decoy in rats resulted in sustained intracellular delivery into macrophages and pulmonary vasculature until 7 days. After MCT injection, rats were divided into no treatment (No Tx) group, and those received single intratracheal decoy alone (50 μg), blank NPs alone, or decoy NP (n=6 – 8, each). No Tx group developed significant PAH, pulmonary arterial remodeling, and increased infiltration of macrophages 3 weeks after MCT injection. These pathologic changes were ameliorated by treatment with decoy NP, but not with decoy only or blank NP only. Increased activity of NF-κB in alveolar macrophages in No Tx group was attenuated by intratracheal decoy NP, but not by decoy only or blank NP only. Conclusions: We have developed a novel Nano-DDS of NF-κB decoy into the lung using bioabsorbable NP, and demonstrated its therapeutic benefit associated with anti-inflammatory effects in MCT-induced PAH. This study provides an innovative future direction of less invasive and dependable Nano-DDS for patients with severe PAH.

scholarly journals Pulmonary Pulse Wave Transit Time is Associated with Right Ventricular–Pulmonary Artery Coupling in Pulmonary Arterial Hypertension

2016 ◽  
Vol 6 (4) ◽  
pp. 576-585 ◽  
Author(s):  
Kurt W. Prins ◽  
E. Kenneth Weir ◽  
Stephen L. Archer ◽  
Jeremy Markowitz ◽  
Lauren Rose ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Transit Time ◽  
Pulse Wave ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Pulse Wave Transit Time ◽  
Pulmonary Arterial

Pulmonary pulse wave transit time (pPTT), defined as the time for the systolic pressure pulse wave to travel from the pulmonary valve to the pulmonary veins, has been reported to be reduced in pulmonary arterial hypertension (PAH); however, the underlying mechanism of reduced pPTT is unknown. Here, we investigate the hypothesis that abbreviated pPTT in PAH results from impaired right ventricular–pulmonary artery (RV-PA) coupling. We quantified pPTT using pulsed-wave Doppler ultrasound from 10 healthy age- and sex-matched controls and 36 patients with PAH. pPTT was reduced in patients with PAH compared with controls. Univariate analysis revealed the following significant predictors of reduced pPTT: age, right ventricular fractional area change (RV FAC), tricuspid annular plane excursion (TAPSE), pulmonary arterial pressures (PAP), diastolic pulmonary gradient, transpulmonary gradient, pulmonary vascular resistance, and RV-PA coupling (defined as RV FAC/mean PAP or TAPSE/mean PAP). Although the correlations between pPTT and invasive markers of pulmonary vascular disease were modest, RV FAC ( r = 0.64, P < 0.0001), TAPSE ( r = 0.67, P < 0.0001), and RV-PA coupling (RV FAC/mean PAP: r = 0.72, P < 0.0001; TAPSE/mean PAP: r = 0.74, P < 0.0001) had the strongest relationships with pPTT. On multivariable analysis, only RV FAC, TAPSE, and RV-PA coupling were independent predictors of pPTT. We conclude that shortening of pPTT in patients with PAH results from altered RV-PA coupling, probably occurring as a result of reduced pulmonary arterial compliance. Thus, pPTT allows noninvasive determination of the status of both the pulmonary vasculature and the response of the RV in patients with PAH, thereby allowing monitoring of disease progression and regression.

scholarly journals 12-Lipoxygenase and 12-hydroxyeicosatetraenoic acid regulate hypoxic angiogenesis and survival of pulmonary artery endothelial cells via PI3K/Akt pathway

2018 ◽  
Vol 314 (4) ◽  
pp. L606-L616 ◽  
Author(s):  
Chen Zhang ◽  
Cui Ma ◽  
Hongmin Yao ◽  
Lixin Zhang ◽  
Xiufeng Yu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Tube Formation ◽  
Pathological Process ◽  
Endothelial Cell Migration ◽  
Pulmonary Vasculature ◽  
Hydroxyeicosatetraenoic Acid ◽  
Therapeutic Concept ◽  
Pulmonary Arterial ◽  
12 Lipoxygenase

Dysfunction and injury of endothelial cells play critical roles in pulmonary arterial hypertension, including aberrant proliferation, suppressed apoptosis, and excessive angiogenesis. The 12-lipoxygenase and 12-hydroxyeicosatetraenoic acid pathway, which has been considered as a crucial mediator, elevates pulmonary vascular resistance and pulmonary arterial pressure. However, the mechanisms underlying the bioactivity of 12-hydroxyeicosatetraenoic acid in pulmonary vasculature, especially in endothelial cells, are still elusive. Thus we aim to determine the key role of 12-lipoxygenase/12-hydroxyeicosatetraenoic acid in angiogenesis and survival of pulmonary artery endothelial cells and ascertain the signaling pathways participating in the pathological process. Here we establish that hypoxia increases the formation of endogenous 12-hydroxyeicosatetraenoic acid through stimulation of 12-lipoxygenase. Furthermore, we put forward new information that 12-hydroxyeicosatetraenoic acid promotes endothelial cell migration and tube formation, whereas it inhibits the serum deprivation-induced apoptotic responses under hypoxia. Particularly, the regulatory effects of 12-lipoxygenase/12-hydroxyeicosatetraenoic acid on pulmonary artery endothelial cells, at least in part, depend on phosphatidylinositol 3-kinase (PI3K)/Akt signaling activation. Taken together, these results may have significant implications for understanding of pulmonary hypertension and offer a potential therapeutic concept focusing on the 12-lipoxygenase/12-hydroxyeicosatetraenoic acid signaling system.

Severe stenosis of a long tracheal segment, with agenesis of the right lung and left pulmonary arterial sling

2006 ◽  
Vol 16 (1) ◽  
pp. 89-91 ◽  
Author(s):  
Hamish M. Munro ◽  
Andrea M. C. Sorbello ◽  
David G. Nykanen
Keyword(s):  
Pulmonary Artery ◽  
Surgical Repair ◽  
Main Bronchus ◽  
Left Lung ◽  
Proximal Part ◽  
Pulmonary Vasculature ◽  
Severe Stenosis ◽  
Right Pulmonary Artery ◽  
Pulmonary Arterial ◽  
The Right

A baby presented at term with respiratory distress was managed with extracorporeal membrane oxygenation. Bronchoscopy revealed tracheal hypoplasia, complete tracheal rings, and agenesis of the right main bronchus. Echocardiography showed a left pulmonary arterial sling arising from the proximal part of the right pulmonary artery. Cardiac catheterization demonstrated abnormal pulmonary vasculature in the left lung which would have prevented survival, even after surgical repair. Diagnostic catheterization was important in delineating the anatomy, and aided in the decision not to proceed with surgical repair.

THE EFFECTS OF MATERNAL HYPOXIA AND HYPEROXIA UPON THE NEONATAL PULMONARY VASCULATURE

PEDIATRICS ◽  
1971 ◽  
Vol 48 (4) ◽  
pp. 528-533 ◽  
Author(s):  
Stanley J. Goldberg ◽  
Richard A. Levy ◽  
Bijan Siassi ◽  
Joanne Betten
Keyword(s):  
Pulmonary Artery ◽  
Pulmonary Arteries ◽  
Pulmonary Vasculature ◽  
External Diameter ◽  
Pulmonary Arterial ◽  
The Mean ◽  
Medial Hypertrophy ◽  
Maternal Hypoxia ◽  
Relationship Of ◽  
Hypoxic Group

The fetal and newborn pulmonary artery has thickened media by comparison to that of the older infant. In this study we investigated the proposition that chronic maternal hypoxia during the latter part of gestation might induce further thickening of the neonatal pulmonary artery media. Relative medial thickness was determined by the ratio of the arterial media to external diameter. The mean ratio of small pulmonary arteries of progeny of hypoxic mothers was significantly thicker in each size group between 50 and 150 microns as compared to those born to mothers who spent their gestation in air or hyperoxic environments. Medial hypertrophy was most pronounced in the smaller arteries of the hypoxic group; no intersize variations were found between the control or hyperoxic groups. Medial thickness decreased in all arteries through 2 weeks of age; this decrease was greatest in control and hyperoxic arteries. The possible relationship of hypertrophied pulmonary arterial media and abnormally increased neonatal pulmonary vascular resistance is discussed.

Chronic in ovo hypoxia decreases pulmonary arterial contractile reactivity and induces biventricular cardiac enlargement in the chicken embryo

2004 ◽  
Vol 287 (3) ◽  
pp. R642-R651 ◽  
Author(s):  
Eduardo Villamor ◽  
Carolina G. A. Kessels ◽  
Karin Ruijtenbeek ◽  
Robert J. van Suylen ◽  
Jaques Belik ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Chicken Embryo ◽  
Experimental Studies ◽  
Left Ventricular ◽  
The Body ◽  
Prenatal Hypoxia ◽  
Pulmonary Vasculature ◽  
Pulmonary Vessel ◽  
Wall Area ◽  
Pulmonary Arterial

Although chronic prenatal hypoxia is considered a major cause of persistent pulmonary hypertension of the newborn, experimental studies have failed to consistently find pulmonary hypertensive changes after chronic intrauterine hypoxia. We hypothesized that chronic prenatal hypoxia induces changes in the pulmonary vasculature of the chicken embryo. We analyzed pulmonary arterial reactivity and structure and heart morphology of chicken embryos maintained from days 6 to 19 of the 21-day incubation period under normoxic (21% O2) or hypoxic (15% O2) conditions. Hypoxia increased mortality (0.46 vs. 0.14; P < 0.01) and reduced the body mass of the surviving 19-day embryos (22.4 ± 0.5 vs. 26.6 ± 0.7 g; P < 0.01). A decrease in the response of the pulmonary artery to KCl was observed in the 19-day hypoxic embryos. The contractile responses to endothelin-1, the thromboxane A2 mimetic U-46619, norepinephrine, and electrical-field stimulation were also reduced in a proportion similar to that observed for KCl-induced contractions. In contrast, no hypoxia-induced decrease of response to vasoconstrictors was observed in externally pipped 21-day embryos (incubated under normoxia for the last 2 days). Relaxations induced by ACh, sodium nitroprusside, or forskolin were unaffected by chronic hypoxia in the pulmonary artery, but femoral artery segments of 19-day hypoxic embryos were significantly less sensitive to ACh than arteries of control embryos [pD2 (= −log EC50): 6.51 ± 0.1 vs. 7.05 ± 0.1, P < 0.01]. Pulmonary vessel density, percent wall area, and periarterial sympathetic nerve density were not different between control and hypoxic embryos. In contrast, hypoxic hearts showed an increase in right and left ventricular wall area and thickness. We conclude that, in the chicken embryo, chronic moderate hypoxia during incubation transiently reduced pulmonary arterial contractile reactivity, impaired endothelium-dependent relaxation of femoral but not pulmonary arteries, and induced biventricular cardiac hypertrophy.

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