Detection of Pathological Changes in the Aorta during Thoracic Aortic Aneurysm Progression on Molecular Level

PubMed Central

Rabajdová, Miroslava; Špaková, Ivana; Panagiotis, Artemiou; Ferenčáková, Michaela; Rybár, Dušan; Bobrov, Nikita; Sabol, František

2017-01-01

The progression of thoracic aortic aneurysm depends on regulation of aortic wall homeostasis and on changes in the structural components of the extracellular matrix, which are affected by multiple molecular signalling pathways. We decided to correlate the diameter of ascending thoracic aneurysm with gene expression of inflammation markers (IL-6, CRP), cytokine receptors (IL-6R, TNFR1, and TNFR2), and extracellular matrix components (Emilin-1, MMP9, and TIMP) for detection of the degree of pathological process of TAA formation. The experimental group was divided into three groups according to the diameter of the aortic aneurysm. Whole blood and tissue samples were properly collected and used for nucleic acid, chromatin, and protein isolation. The mRNA levels were detected by qRT-PCR. For the detection of protein levels a Cytokine Array IV assay kit was used in combination with a biochip analyzer. In aortic tissue, significant positive correlations were found between increased mRNA levels of inflammatory cytokines (CRP and IL-6) on both mRNA levels in tissue and protein from the blood with maximum in stage 3. Changes of gene expression of selected genes can be used for the experimental study of the inflammatory receptor inhibitors during trials targeted on slowing down the progress of aortic wall aneurysm. PMID:29158612

Mechanical deterioration underlies malignant behavior of aneurysmal human ascending aorta.

PubMed

Koullias, George; Modak, Raj; Tranquilli, Maryann; Korkolis, Dimitris P; Barash, Paul; Elefteriades, John A

2005-09-01

The human ascending aorta becomes markedly prone to rupture and dissection at a diameter of 6 cm. The mechanical substrate for this malignant behavior is unknown. This investigation applied engineering analysis to human ascending aortic aneurysms and compared their structural characteristics with those of normal aortas. We measured the mechanical characteristics of the aorta by direct epiaortic echocardiography at the time of surgery in 33 patients with ascending aortic aneurysm undergoing aortic replacement and in 20 control patients with normal aortas undergoing coronary artery bypass grafting. Six parameters were measured in all patients: aortic diameter in systole and diastole, aortic wall thickness in systole and diastole, and blood pressure in systole and diastole. These were used to calculate mechanical characteristics of the aorta from standard equations. Aortic distensibility reflects the elastic qualities of the aorta. Aortic wall stress reflects the disrupting force experienced within the aortic wall. Incremental elastic modulus indicates loss of elasticity reserve. Aortic distensibility falls to extremely low levels as aortic dimension rises toward 6 cm (3.02 mm Hg(-1) for small aortas versus 1.45 mm Hg(-1) for aortas larger than 5 cm, P < .05). Aortic wall stress rises to 157.8 kPa for the aneurysmal aorta, compared with 92.5 kPa for normal aortas. For 6-cm aortas at pressures of 200 mm Hg or more, wall stress rises to 857 kPa, nearly exceeding the known maximal tensile strength of human aneurysmal aortic wall. Incremental elastic modulus deteriorates (1.93 +/- 0.88 MPa vs 1.18 +/- 0.21 MPa, P < .05) in aneurysmal aortas relative to that in normal aortas. The mechanical properties of the aneurysmal aorta deteriorate dramatically as the aorta enlarges, reaching critical levels associated with rupture by a diameter of 6 cm. This mechanical deterioration provides an explanation in engineering terms for the malignant clinical behavior (rupture and dissection) of the aorta at these dimensions. This work adds to our fundamental understanding of the biology of aortic aneurysms and promises to permit future application of engineering measurements to supplement aneurysm size in clinical decision making in aneurysmal disease.

Characterization of the mechanical behavior and pathophysiological state of abdominal aortic aneurysms based on 4D ultrasound strain imaging

NASA Astrophysics Data System (ADS)

Wittek, Andreas; Blase, Christopher; Derwich, Wojciech; Schmitz-Rixen, Thomas; Fritzen, Claus-Peter

2017-06-01

Abdominal aortic aneurysms (AAA) are a degenerative disease of the human aortic wall that may lead to weakening and eventually rupture of the wall with high mortality rates. Since the currently established criterion for surgical or endovascular treatment of the disease is imprecise in the individual case and treatment is not free of complications, the need for additional patient-individual biomarkers for short-term AAA rupture risk as basis for improved clinical decision making. Time resolved 3D ultrasound combined with speckle tracking algorithms is a novel non-invasive medical imaging technique that provides full-field displacement and strain measurements of aortic and aneurysmal wall motion. This is patient-individual information that has not been used so far to assess wall strength and rupture risk. The current study uses simple statistical indices of the heterogeneous spatial distribution of in-plane strain components as biomarkers for the pathological state of the aortic and aneurysmal wall. The pathophysiological rationale behind this approach are the known changes in microstructural composition of the aortic wall with progression of AAA development that results in increased stiffening and heterogeneity of the walls mechanical properties and in decreased wall strength. In a comparative analysis of the aortic wall motion of young volunteers without known cardiovascular diseases, aged arteriosclerotic patients without AAA, and AAA patients, mean values of all in-plane strain components were significantly reduced, and the heterogeneity of circumferential strain was significantly increased in the AAA group compared to both other groups. The capacity of the proposed method to differentiate between wall motion of aged, arteriosclerotic patients and AAA patients is a promising step towards a new method for in vivo assessment of AAA wall strength or stratification of AAA rupture risk as basis for improved clinical decision making on surgical or endovascular treatment of AAA.

CXCL8 hyper-signaling in the aortic abdominal aneurysm.

PubMed

Kokje, Vivianne B C; Gäbel, Gabor; Dalman, Ron L; Koole, Dave; Northoff, Bernd H; Holdt, Lesca M; Hamming, Jaap F; Lindeman, Jan H N

2018-08-01

There are indications for elevated CXCL8 levels in abdominal aortic aneurysm disease (AAA). CXCL8 is concurrently involved in neutrophil-mediated inflammation and angiogenesis, two prominent and distinctive characteristics of AAA. As such we considered an evaluation of a role for CXCL8 in AAA progression relevant. ELISA's, real time PCR and array analysis were used to explore CXCL8 signaling in AAA wall samples. A role for CXCL8 in AAA disease was tested through the oral CXCR1/2 antagonist DF2156A in the elastase model of AAA disease. There is an extreme disparity in aortic wall CXCL8 content between AAA and aortic atherosclerotic disease (median [IQR] aortic wall CXCL8 content: 425 [141-1261] (AAA) vs. 23 [2.8-89] (atherosclerotic aorta) µg/g protein (P < 1 · 10 -14 )), and abundant expression of the CXCR1 and 2 receptors in AAA. Array analysis followed by pathway analysis showed that CXCL8 hyper-expression in AAA is followed increased by IL-8 signaling (Z-score for AAA vs. atherosclerotic control: 2.97, p < 0.0001). Interference with CXCL8 signaling through DF2156A fully abrogated AAA formation and prevented matrix degradation in the murine elastase model of AAA disease (p < 0.001). CXCL8-signaling is a prominent and distinctive feature of AAA, interference with the pathway constitutes a promising target for medical stabilization of AAA. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effects of intra-aortic counterpulsation on aortic wall energetics and damping: in vivo experiments.

PubMed

Fischer, Edmundo I Cabrera; Bia, Daniel; Camus, Juan M; Zócalo, Yanina; de Forteza, Eduardo; Armentano, Ricardo L

2008-01-01

Intra-aortic balloon pumping (IABP) could modify the arterial biomechanics; however, its effects on arterial wall properties have not been fully explored. This dynamical study was designed to characterize the pressure-dependent and smooth muscle-dependent effects of IABP on aortic wall energetics in an in vivo animal model. Intra-aortic balloon pumping (1:2) was performed in six anesthetized sheep in which aortic pressure and diameter signals were measured in basal, augmented (during balloon inflation), and assisted (postaugmented) beats. Energy dissipation values in augmented and assisted beats were significantly higher than those observed in basal state (p < 0.05). Assisted beats showed a significant increase of wall damping with respect to basal and augmented beats (p < 0.05). Intra-aortic balloon pumping resulted in a significant increase of pulse wave velocity (p < 0.05) in augmented beats with respect to basal state (6.3 +/- 0.8 vs. 5.2 +/- 0.5 m x s(-1)); whereas values observed in assisted beats were significantly (p < 0.05) lower than those observed in augmented beats (4.9 +/- 0.5 vs. 6.3 +/- 0.8 m x s(-1)). Our findings show that IABP determined the pressure and smooth muscle-dependent changes in arterial wall energetics and damping properties in this animal model.

Agreement between methods of measurement of mean aortic wall thickness by MRI.

PubMed

Rosero, Eric B; Peshock, Ronald M; Khera, Amit; Clagett, G Patrick; Lo, Hao; Timaran, Carlos

2009-03-01

To assess the agreement between three methods of calculation of mean aortic wall thickness (MAWT) using magnetic resonance imaging (MRI). High-resolution MRI of the infrarenal abdominal aorta was performed on 70 subjects with a history of coronary artery disease who were part of a multi-ethnic population-based sample. MAWT was calculated as the mean distance between the adventitial and luminal aortic boundaries using three different methods: average distance at four standard positions (AWT-4P), average distance at 100 automated positions (AWT-100P), and using a mathematical computation derived from the total vessel and luminal areas (AWT-VA). Bland-Altman plots and Passing-Bablok regression analyses were used to assess agreement between methods. Bland-Altman analyses demonstrated a positive bias of 3.02+/-7.31% between the AWT-VA and the AWT-4P methods, and of 1.76+/-6.82% between the AWT-100P and the AWT-4P methods. Passing-Bablok regression analyses demonstrated constant bias between the AWT-4P method and the other two methods. Proportional bias was, however, not evident among the three methods. MRI methods of measurement of MAWT using a limited number of positions of the aortic wall systematically underestimate the MAWT value compared with the method that calculates MAWT from the vessel areas. Copyright (c) 2009 Wiley-Liss, Inc.

Dynamic autophagic activity affected the development of thoracic aortic dissection by regulating functional properties of smooth muscle cells

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

Wang, Yang; Zhao, Zhi-Min; Zhang, Guan-Xin

The aortic medial degeneration is the key histopathologic feature of Thoracic aortic dissection (TAD). The aim of this study was to identify the change of autophagic activity in the aortic wall during TAD development, and to explore the roles of autophagy on regulating functional properties of smooth muscle cells (SMCs). Firstly, compared with control group (n = 11), the increased expression of autophagic markers Beclin1 and LC3 was detected in the aortic wall from TAD group (n = 23) by immunochemistry and western blot. We found that more autophagic vacuoles were present in the aortic wall of TAD patients using Transmission electron microscopy. Next,more » autophagic activity was examined in AD mice model established by β-aminopropionitrile fumarate (BAPN) and angiotensin II. Immunochemistry proved that autophagic activity was dynamically changed during AD development. Beclin1 and LC3 were detected up-regulated in the aortic wall in the second week after BAPN feeding, earlier than the fragmentation or loss of elastic fibers. When AD occurred in the 4th week, the expression of Beclin1 and LC3 began to decrease, but still higher than the control. Furthermore, autophagy was found to inhibit starvation-induced apoptosis of SMCs. Meanwhile, blockage of autophagy could suppress PDGF-induced phenotypic switch of SMCs. Taken together, autophagic activity was dynamically changed in the aortic wall during TAD development. The abnormal autophagy could regulate the functional properties of aortic SMCs, which might be the potential pathogenesis of TAD. - Highlights: • Autophagy is up-regulated in aorta wall from thoracic aorta dissection (TAD) patient. • Autophagic activity is dynamically changed during TAD development. • Dynamically change of autophagy is associated with pathological process of TAD. • Autophagy participate in the development of TAD by regulating function of SMCs.« less

Optical coherence tomography assessment of vessel wall degradation in aneurysmatic thoracic aortas

NASA Astrophysics Data System (ADS)

Real, Eusebio; Eguizabal, Alma; Pontón, Alejandro; Val-Bernal, J. Fernando; Mayorga, Marta; Revuelta, José M.; López-Higuera, José; Conde, Olga M.

2013-06-01

Optical coherence tomographic images of ascending thoracic human aortas from aneurysms exhibit disorders on the smooth muscle cell structure of the media layer of the aortic vessel as well as elastin degradation. Ex-vivo measurements of human samples provide results that correlate with pathologist diagnosis in aneurysmatic and control aortas. The observed disorders are studied as possible hallmarks for aneurysm diagnosis. To this end, the backscattering profile along the vessel thickness has been evaluated by fitting its decay against two different models, a third order polynomial fitting and an exponential fitting. The discontinuities present on the vessel wall on aneurysmatic aortas are slightly better identified with the exponential approach. Aneurysmatic aortic walls present uneven reflectivity decay when compared with healthy vessels. The fitting error has revealed as the most favorable indicator for aneurysm diagnosis as it provides a measure of how uniform is the decay along the vessel thickness.

Effects of aortic root motion on wall stress in the Marfan aorta before and after personalised aortic root support (PEARS) surgery.

PubMed

Singh, S D; Xu, X Y; Pepper, J R; Izgi, C; Treasure, T; Mohiaddin, R H

2016-07-05

Aortic root motion was previously identified as a risk factor for aortic dissection due to increased longitudinal stresses in the ascending aorta. The aim of this study was to investigate the effects of aortic root motion on wall stress and strain in the ascending aorta and evaluate changes before and after implantation of personalised external aortic root support (PEARS). Finite element (FE) models of the aortic root and thoracic aorta were developed using patient-specific geometries reconstructed from pre- and post-PEARS cardiovascular magnetic resonance (CMR) images in three Marfan patients. The wall and PEARS materials were assumed to be isotropic, incompressible and linearly elastic. A static load on the inner wall corresponding to the patients' pulse pressure was applied. Cardiovascular MR cine images were used to quantify aortic root motion, which was imposed at the aortic root boundary of the FE model, with zero-displacement constraints at the distal ends of the aortic branches and descending aorta. Measurements of the systolic downward motion of the aortic root revealed a significant reduction in the axial displacement in all three patients post-PEARS compared with its pre-PEARS counterparts. Higher longitudinal stresses were observed in the ascending aorta when compared with models without the root motion. Implantation of PEARS reduced the longitudinal stresses in the ascending aorta by up to 52%. In contrast, the circumferential stresses at the interface between the supported and unsupported aorta were increase by up to 82%. However, all peak stresses were less than half the known yield stress for the dilated thoracic aorta. Copyright © 2016 Elsevier Ltd. All rights reserved.

Three-dimensional imaging of the aortic vessel wall using an elastin-specific magnetic resonance contrast agent.

PubMed

Makowski, Marcus R; Preissel, Anne; von Bary, Christian; Warley, Alice; Schachoff, Sylvia; Keithan, Alexandra; Cesati, Richard R; Onthank, David C; Schwaiger, Markus; Robinson, Simon P; Botnar, René M

2012-07-01

The aim of this study was to demonstrate the feasibility of high-resolution 3-dimensional aortic vessel wall imaging using a novel elastin-specific magnetic resonance contrast agent (ESMA) in a large animal model. The thoracic aortic vessel wall of 6 Landrace pigs was imaged using a novel ESMA and a nonspecific control agent. On day 1, imaging was performed before and after the administration of a nonspecific control agent, gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA; Bayer Schering AG, Berlin, Germany). On day 3, identical scans were repeated before and after the administration of a novel ESMA (Lantheus Medical Imaging, North Billerica, Massachusetts). Three-dimensional inversion recovery gradient echo delayed-enhancement imaging and magnetic resonance (MR) angiography of the thoracic aortic vessel wall were performed on a 1.5-T MR scanner (Achieva; Philips Medical Systems, the Netherlands). The signal-to-noise ratio and the contrast-to-noise ratio of arterial wall enhancement, including the time course of enhancement, were assessed for ESMA and Gd-DTPA. After the completion of imaging sessions, histology, electron microscopy, and inductively coupled plasma mass spectroscopy were performed to localize and quantify the gadolinium bound to the arterial vessel wall. Administration of ESMA resulted in a strong enhancement of the aortic vessel wall on delayed-enhancement imaging, whereas no significant enhancement could be measured with Gd-DTPA. Ninety to 100 minutes after the administration of ESMA, significantly higher signal-to-noise ratio and contrast-to-noise ratio could be measured compared with the administration of Gd-DTPA (45.7 ± 9.6 vs 13.2 ± 3.5, P < 0.05 and 41.9 ± 9.1 vs 5.2 ± 2.0, P < 0.05). A significant correlation (0.96; P < 0.01) between area measurements derived from ESMA scans and aortic MR angiography scans could be found. Electron microscopy and inductively coupled plasma mass spectroscopy confirmed the colocalization of ESMA with elastic fibers. We demonstrate the feasibility of aortic vessel wall imaging using a novel ESMA in a large animal model under conditions resembling a clinical setting. Such an approach could be useful for the fast 3-dimensional assessment of the arterial vessel wall in the context of atherosclerosis, aortic aneurysms, and hypertension.

Arterial elastic fiber structure. Function and potential roles in acute aortic dissection.

PubMed

Pratt, B; Curci, J

2010-10-01

The lethality of acute aortic dissection is well recognized. Successful treatment and prevention of aortic dissection is going to be dependent upon an improved understanding of the molecular and physiologic events which predispose to dissection development and propagation. In this review, we will focus on the elastic fiber, one of the critical elements of the aortic wall matrix. Mechanical or functional failure of the elastin in the wall of the aorta likely predisposes to dissection as well as the post-dissection aortic degeneration with aneurysm formation. Insight into the role of the elastin and the elastic fiber in aortic dissection has recently been accelerated by research into the molecular mechanisms associated with hereditary propensity for aortic dissection, such as Marfan syndrome. These studies have implicated both structural and metabolic contributions of alterations in the scaffolding proteins in matrix elastic fibers. In particular, increased transforming growth factor-β (TGF-β) activity may play a prominent role in predisposing the aortic wall to dissection. The events which predispose to post-dissection aortic degeneration are somewhat less well defined. However, the loss of the structural integrity of the remaining elastic fibers leaves the wall weaker and prone to dilatation and rupture. It appears likely that the upregulation of several potent proteases, particularly those of the matrix metalloproteinase (MMP) family such as MMP-9, are participating in the subsequent matrix damage. Novel medical treatments based on this pathologic data have been proposed and in some cases have made it to clinical trials. The ongoing study evaluating whether therapeutic inhibition of TGF-β may be useful in reducing the risk of aortic dissection in patients at high risk represents one promising new strategy in the treatment of this deadly disease.

Biomechanical properties of the Marfan's aortic root and ascending aorta before and after personalised external aortic root support surgery.

PubMed

Singh, S D; Xu, X Y; Pepper, J R; Treasure, T; Mohiaddin, R H

2015-08-01

Marfan syndrome is an inherited systemic connective tissue disease which may lead to aortic root disease causing dilatation, dissection and rupture of the aorta. The standard treatment is a major operation involving either an artificial valve and aorta or a complex valve repair. More recently, a personalised external aortic root support (PEARS) has been used to strengthen the aorta at an earlier stage of the disease avoiding risk of both rupture and major surgery. The aim of this study was to compare the stress and strain fields of the Marfan aortic root and ascending aorta before and after insertion of PEARS in order to understand its biomechanical implications. Finite element (FE) models were developed using patient-specific aortic geometries reconstructed from pre and post-PEARS magnetic resonance images in three Marfan patients. For the post-PEARS model, two scenarios were investigated-a bilayer model where PEARS and the aortic wall were treated as separate layers, and a single-layer model where PEARS was incorporated into the aortic wall. The wall and PEARS materials were assumed to be isotropic, incompressible and linearly elastic. A static load on the inner wall corresponding to the patients' pulse pressure was applied. Results from our FE models with patient-specific geometries show that peak aortic stresses and displacements before PEARS were located at the sinuses of Valsalva but following PEARS surgery, these peak values were shifted to the aortic arch, particularly at the interface between the supported and unsupported aorta. Further studies are required to assess the statistical significance of these findings and how PEARS compares with the standard treatment. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

Abscisic acid ameliorates atherosclerosis by suppressing macrophage and CD4+ T cell recruitment into the aortic wall

PubMed Central

Guri, Amir J.; Misyak, Sarah A.; Hontecillas, Raquel; Hasty, Alyssa; Liu, Dongmin; Si, Hongwei; Bassaganya-Riera, Josep

2009-01-01

Abscisic acid (ABA) is a natural phytohormone which improves insulin sensitivity and reduces adipose tissue inflammation when supplemented into diets of obese mice. The objective of this study was to investigate the mechanisms by which abscisic acid (ABA) prevents or ameliorates atherosclerosis. Apolipoprotein E-deficient (ApoE −/−) mice were fed high-fat diets with or without ABA for 84 days. Systolic blood pressure was assessed on days 0, 28, 56, and 72. Gene expression, immune cell infiltration, and histological lesions were evaluated in the aortic root wall. Human aortic endothelial cells were used to examine the effect of ABA on 3’, 5’-cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) production in vitro. We report that ABA-treated mice had significantly improved systolic blood pressure and decreased accumulation of F4/80+CD11b+ macrophages and CD4+ T cells in aortic root walls. At the molecular level, ABA significantly enhanced aortic endothelial nitric oxide synthase (eNOS) and tended to suppress aortic vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) expression and plasma MCP-1 concentrations. ABA also caused a dose-dependent increase in intracellular concentrations of cAMP and NO and upregulated eNOS mRNA expression in human aortic endothelial cells. This is the first report showing that ABA prevents or ameliorates atherosclerosis-induced hypertension, immune cell recruitment into the aortic root wall, and upregulates aortic eNOS expression in ApoE−/− mice. PMID:20092994

Abscisic acid ameliorates atherosclerosis by suppressing macrophage and CD4+ T cell recruitment into the aortic wall.

PubMed

Guri, Amir J; Misyak, Sarah A; Hontecillas, Raquel; Hasty, Alyssa; Liu, Dongmin; Si, Hongwei; Bassaganya-Riera, Josep

2010-12-01

Abscisic acid (ABA) is a natural phytohormone which improves insulin sensitivity and reduces adipose tissue inflammation when supplemented into diets of obese mice. The objective of this study was to investigate the mechanisms by which ABA prevents or ameliorates atherosclerosis. apolipoprotein E-deficient (ApoE(-/-)) mice were fed high-fat diets with or without ABA for 84 days. Systolic blood pressure was assessed on Days 0, 28, 56 and 72. Gene expression, immune cell infiltration and histological lesions were evaluated in the aortic root wall. Human aortic endothelial cells were used to examine the effect of ABA on 3',5'-cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) production in vitro. We report that ABA-treated mice had significantly improved systolic blood pressure and decreased accumulation of F4/80(+)CD11b(+) macrophages and CD4(+) T cells in aortic root walls. At the molecular level, ABA significantly enhanced aortic endothelial nitric oxide synthase (eNOS) and tended to suppress aortic vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) expression and plasma MCP-1 concentrations. ABA also caused a dose-dependent increase in intracellular concentrations of cAMP and NO and up-regulated eNOS mRNA expression in human aortic endothelial cells. This is the first report showing that ABA prevents or ameliorates atherosclerosis-induced hypertension, immune cell recruitment into the aortic root wall and up-regulates aortic eNOS expression in ApoE(-/-) mice. Copyright © 2010 Elsevier Inc. All rights reserved.

Evaluation of Aortic Blood Flow and Wall Shear Stress in Aortic Stenosis and Its Association With Left Ventricular Remodeling.

PubMed

von Knobelsdorff-Brenkenhoff, Florian; Karunaharamoorthy, Achudhan; Trauzeddel, Ralf Felix; Barker, Alex J; Blaszczyk, Edyta; Markl, Michael; Schulz-Menger, Jeanette

2016-03-01

Aortic stenosis (AS) leads to variable stress for the left ventricle (LV) and consequently a broad range of LV remodeling. The aim of this study was to describe blood flow patterns in the ascending aorta of patients with AS and determine their association with remodeling. Thirty-seven patients with AS (14 mild, 8 moderate, 15 severe; age, 63±13 years) and 37 healthy controls (age, 60±10 years) underwent 4-dimensional-flow magnetic resonance imaging. Helical and vortical flow formations and flow eccentricity were assessed in the ascending aorta. Normalized flow displacement from the vessel center and peak systolic wall shear stress in the ascending aorta were quantified. LV remodeling was assessed based on LV mass index and the ratio of LV mass:end-diastolic volume (relative wall mass). Marked helical and vortical flow formation and eccentricity were more prevalent in patients with AS than in healthy subjects, and patients with AS exhibited an asymmetrical and elevated distribution of peak systolic wall shear stress. In AS, aortic orifice area was strongly negatively associated with vortical flow formation (P=0.0274), eccentricity (P=0.0070), and flow displacement (P=0.0021). Bicuspid aortic valve was associated with more intense helical (P=0.0098) and vortical flow formation (P=0.0536), higher flow displacement (P=0.11), and higher peak systolic wall shear stress (P=0.0926). LV mass index and relative wall mass were significantly associated with aortic orifice area (P=0.0611, P=0.0058) and flow displacement (P=0.0058, P=0.0283). In this pilot study, AS leads to abnormal blood flow pattern and peak systolic wall shear stress in the ascending aorta. In addition to aortic orifice area, normalized flow displacement was significantly associated with LV remodeling. © 2016 American Heart Association, Inc.

The effects of nicotine administration on the pathophysiology of rat aortic wall.

PubMed

Kugo, H; Zaima, N; Tanaka, H; Urano, T; Unno, N; Moriyama, T

2017-01-01

Abdominal aortic aneurysm (AAA) is the progressive dilation of the abdominal aorta. Nicotine is reported to be associated with the development and rupture of AAA, but the pathological effects of nicotine on normal rat aorta have not been determined. We investigated pathological changes in the aortic wall of rats caused by the administration of nicotine. Nicotine administration weakened the vascular wall, increased gelatinolytic activity and promoted the destruction of elastin and collagen in the rat abdominal aorta. There were no differences in the areas positive for matrix metalloproteinase (MMP)-2 and MMP-9 between the control and nicotine treated groups. The areas positive for MMP-12 in the nicotine group were significantly greater than for the control group. Gelatinolytic activity in the aortic wall was increased significantly in the nicotine group. Our findings suggest that MMP-12 is sensitive to nicotine exposure in rats.

On the prediction of monocyte deposition in abdominal aortic aneurysms using computational fluid dynamics.

PubMed

Hardman, David; Doyle, Barry J; Semple, Scott I K; Richards, Jennifer M J; Newby, David E; Easson, William J; Hoskins, Peter R

2013-10-01

In abdominal aortic aneurysm disease, the aortic wall is exposed to intense biological activity involving inflammation and matrix metalloproteinase-mediated degradation of the extracellular matrix. These processes are orchestrated by monocytes and rather than affecting the aorta uniformly, damage and weaken focal areas of the wall leaving it vulnerable to rupture. This study attempts to model numerically the deposition of monocytes using large eddy simulation, discrete phase modelling and near-wall particle residence time. The model was first applied to idealised aneurysms and then to three patient-specific lumen geometries using three-component inlet velocities derived from phase-contrast magnetic resonance imaging. The use of a novel, variable wall shear stress-limiter based on previous experimental data significantly improved the results. Simulations identified a critical diameter (1.8 times the inlet diameter) beyond which significant monocyte deposition is expected to occur. Monocyte adhesion occurred proximally in smaller abdominal aortic aneurysms and distally as the sac expands. The near-wall particle residence time observed in each of the patient-specific models was markedly different. Discrete hotspots of monocyte residence time were detected, suggesting that the monocyte infiltration responsible for the breakdown of the abdominal aortic aneurysm wall occurs heterogeneously. Peak monocyte residence time was found to increase with aneurysm sac size. Further work addressing certain limitations is needed in a larger cohort to determine clinical significance.

Disruption of mechanical stress in extracellular matrix is related to Stanford type A aortic dissection through down-regulation of Yes-associated protein.

PubMed

Jiang, Wen-Jian; Ren, Wei-Hong; Liu, Xu-Jie; Liu, Yan; Wu, Fu-Jian; Sun, Li-Zhong; Lan, Feng; Du, Jie; Zhang, Hong-Jia

2016-09-05

In this study, we assessed whether the down-regulation of Yes-associated protein (YAP) is involved in the pathogenesis of extracellular matrix (ECM) mechanical stress-induced Stanford type A aortic dissection (STAAD). Human aortic samples were obtained from heart transplantation donors as normal controls and from STAAD patients undergoing surgical replacement of the ascending aorta. Decreased maximum aortic wall velocity, ECM disorders, increased VSMC apoptosis, and YAP down-regulation were identified in STAAD samples. In a mouse model of STAAD, YAP was down-regulated over time during the development of ECM damage, and increased VSMC apoptosis was also observed. YAP knockdown induced VSMC apoptosis under static conditions in vitro , and the change in mechanical stress induced YAP down-regulation and VSMC apoptosis. This study provides evidence that YAP down-regulation caused by the disruption of mechanical stress is associated with the development of STAAD via the induction of apoptosis in aortic VSMCs. As STAAD is among the most elusive and life-threatening vascular diseases, better understanding of the molecular pathogenesis of STAAD is critical to improve clinical outcome.

Fourier Transform Infrared Spectroscopic Imaging-Derived Collagen Content and Maturity Correlates with Stress in the Aortic Wall of Abdominal Aortic Aneurysm Patients.

PubMed

Cheheltani, Rabee; Pichamuthu, Joseph E; Rao, Jayashree; Weinbaum, Justin S; Kiani, Mohammad F; Vorp, David A; Pleshko, Nancy

2017-03-01

Abdominal aortic aneurysm (AAA) is a degenerative disease of the aorta characterized by severe disruption of the structural integrity of the aortic wall and its major molecular constituents. From the early stages of disease, elastin in the aorta becomes highly degraded and is replaced by collagen. Questions persist as to the contribution of collagen content, quality and maturity to the potential for rupture. Here, using our recently developed Fourier transform infrared imaging spectroscopy (FT-IRIS) method, we quantified collagen content and maturity in the wall of AAA tissues in pairs of specimens with different wall stresses. CT scans of AAAs from 12 patients were used to create finite element models to estimate stress in different regions of tissue. Each patient underwent elective repair of the AAA, and two segments of the AAA tissues from anatomic regions more proximal or distal with different wall stresses were evaluated by histology and FT-IRIS after excision. For each patient, collagen content was generally greater in the tissue location with lower wall stress, which corresponded to the more distal anatomic regions. The wall stress/collagen ratio was greater in the higher stress region compared to the lower stress region (1.01 ± 1.09 vs. 0.55 ± 0.084, p = 0.02). The higher stress region also corresponded to the location with reduced intraluminal thrombus thickness. Further, collagen maturity tended to decrease with increased collagen content (p = 0.068, R = 0.38). Together, these results suggest that an increase in less mature collagen content in AAA patients does not effectively compensate for the loss of elastin in the aortic wall, and results in a reduced capability to endure wall stresses.

Pulsatile flows and wall-shear stresses in models simulating normal and stenosed aortic arches

NASA Astrophysics Data System (ADS)

Huang, Rong Fung; Yang, Ten-Fang; Lan, Y.-K.

2010-03-01

Pulsatile aqueous glycerol solution flows in the models simulating normal and stenosed human aortic arches are measured by means of particle image velocimetry. Three transparent models were used: normal, 25% stenosed, and 50% stenosed aortic arches. The Womersley parameter, Dean number, and time-averaged Reynolds number are 17.31, 725, and 1,081, respectively. The Reynolds numbers based on the peak velocities of the normal, 25% stenosed, and 50% stenosed aortic arches are 2,484, 3,456, and 3,931, respectively. The study presents the temporal/spatial evolution processes of the flow pattern, velocity distribution, and wall-shear stress during the systolic and diastolic phases. It is found that the flow pattern evolving in the central plane of normal and stenosed aortic arches exhibits (1) a separation bubble around the inner arch, (2) a recirculation vortex around the outer arch wall upstream of the junction of the brachiocephalic artery, (3) an accelerated main stream around the outer arch wall near the junctions of the left carotid and the left subclavian arteries, and (4) the vortices around the entrances of the three main branches. The study identifies and discusses the reasons for the flow physics’ contribution to the formation of these features. The oscillating wall-shear stress distributions are closely related to the featured flow structures. On the outer wall of normal and slightly stenosed aortas, large wall-shear stresses appear in the regions upstream of the junction of the brachiocephalic artery as well as the corner near the junctions of the left carotid artery and the left subclavian artery. On the inner wall, the largest wall-shear stress appears in the region where the boundary layer separates.

In Silico Shear and Intramural Stresses are Linked to Aortic Valve Morphology in Dilated Ascending Aorta.

PubMed

Pasta, S; Gentile, G; Raffa, G M; Bellavia, D; Chiarello, G; Liotta, R; Luca, A; Scardulla, C; Pilato, M

2017-08-01

The development of ascending aortic dilatation in patients with bicuspid aortic valve (BAV) is highly variable, and this makes surgical decision strategies particularly challenging. The purpose of this study was to identify new predictors, other than the well established aortic size, that may help to stratify the risk of aortic dilatation in BAV patients. Using fluid-structure interaction analysis, both haemodynamic and structural parameters exerted on the ascending aortic wall of patients with either BAV (n = 21) or tricuspid aortic valve (TAV; n = 13) with comparable age and aortic diameter (42.7 ± 5.3 mm for BAV and 45.4 ± 10.0 mm for TAV) were compared. BAV phenotypes were stratified according to the leaflet fusion pattern and aortic shape. Systolic wall shear stress (WSS) of BAV patients was higher than TAV patients at the sinotubular junction (6.8 ± 3.3 N/m 2 for BAV and 3.9 ± 1.3 N/m 2 for TAV; p = .006) and mid-ascending aorta (9.8 ± 3.3 N/m 2 for BAV and 7.1 ± 2.3 N/m 2 for TAV; p = .040). A statistically significant difference in BAV versus TAV was also observed for the intramural stress along the ascending aorta (e.g., 2.54 × 10 5  ± 0.32 × 10 5  N/m 2 for BAV and 2.04 × 10 5  ± 0.34 × 10 5  N/m 2 for TAV; p < .001) and pressure index (0.329 ± 0.107 for BAV and 0.223 ± 0.139 for TAV; p = .030). Differences in the BAV phenotypes (i.e., BAV type 1 vs. BAV type 2) and aortopathy (i.e., isolated tubular vs. aortic root dilatations) were associated with asymmetric WSS distributions in the right anterior aortic wall and right posterior aortic wall, respectively. These findings suggest that valve mediated haemodynamic and structural parameters may be used to identify which regions of aortic wall are at greater stress and enable the development of a personalised approach for the diagnosis and management of aortic dilatation beyond traditional guidelines. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Histology and Biaxial Mechanical Behavior of Abdominal Aortic Aneurysm Tissue Samples.

PubMed

Pancheri, Francesco Q; Peattie, Robert A; Reddy, Nithin D; Ahamed, Touhid; Lin, Wenjian; Ouellette, Timothy D; Iafrati, Mark D; Luis Dorfmann, A

2017-03-01

Abdominal aortic aneurysms (AAAs) represent permanent, localized dilations of the abdominal aorta that can be life-threatening if progressing to rupture. Evaluation of risk of rupture depends on understanding the mechanical behavior of patient AAA walls. In this project, a series of patient AAA wall tissue samples have been evaluated through a combined anamnestic, mechanical, and histopathologic approach. Mechanical properties of the samples have been characterized using a novel, strain-controlled, planar biaxial testing protocol emulating the in vivo deformation of the aorta. Histologically, the tissue ultrastructure was highly disrupted. All samples showed pronounced mechanical stiffening with stretch and were notably anisotropic, with greater stiffness in the circumferential than the axial direction. However, there were significant intrapatient variations in wall stiffness and stress. In biaxial tests in which the longitudinal stretch was held constant at 1.1 as the circumferential stretch was extended to 1.1, the maximum average circumferential stress was 330 ± 70 kPa, while the maximum average axial stress was 190 ± 30 kPa. A constitutive model considering the wall as anisotropic with two preferred directions fit the measured data well. No statistically significant differences in tissue mechanical properties were found based on patient gender, age, maximum bulge diameter, height, weight, body mass index, or smoking history. Although a larger patient cohort is merited to confirm these conclusions, the project provides new insight into the relationships between patient natural history, histopathology, and mechanical behavior that may be useful in the development of accurate methods for rupture risk evaluation.

Effect of Selenium Supplementation on Redox Status of the Aortic Wall in Young Spontaneously Hypertensive Rats

PubMed Central

Ruseva, Boryana; Atanasova, Milena; Tsvetkova, Reni; Betova, Tatyana; Mollova, Margarita; Alexandrova, Margarita; Laleva, Pavlina; Dimitrova, Aneliya

2015-01-01

Selenium (Se) is an exogenous antioxidant that performs its function via the expression of selenoproteins. The aim of this study was to explore the effect of varying Se intake on the redox status of the aortic wall in young spontaneously hypertensive rats (SHR). Sixteen male Wistar Kyoto (WKY) rats and nineteen male SHR, 16-week-old, were tested after being given diets with different Se content for eight weeks. They were divided into 4 groups: control groups of WKY NSe and SHR NSe on an adequate Se diet and groups of WKY HSe and SHR HSe that received Se supplementation. The Se nutritional status was assessed by measuring whole blood glutathione peroxidase-1 (GPx-1) activity. Serum concentration of lipid hydroperoxides and serum level of antibodies against advanced glycation end products (anti-AGEs abs) were determined. Expression of GPx-1 and endothelial nitric oxide synthase (eNOS) were examined in aortic wall. Se supplementation significantly increased GPx-1 activity of whole blood and in the aortas of WKY and SHR. Decreased lipid peroxidation level, eNOS-3 expression in the aortic wall, and serum level of anti-AGEs abs were found in SHR HSe compared with SHR NSe. In conclusion, Se supplementation improved the redox status of the aortic wall in young SHR. PMID:26473024

High levels of thyroid-stimulating hormone are associated with aortic wall thickness in the general population.

PubMed

Ittermann, Till; Lorbeer, Roberto; Dörr, Marcus; Schneider, Tobias; Quadrat, Alexander; Heßelbarth, Lydia; Wenzel, Michael; Lehmphul, Ina; Köhrle, Josef; Mensel, Birger; Völzke, Henry

2016-12-01

Our aim was to investigate the association of thyroid function defined by serum concentrations of thyroid-stimulating hormone (TSH) with thoracic aortic wall thickness (AWT) as a marker of atherosclerotic processes. We pooled data of 2,679 individuals from two independent population-based surveys of the Study of Health in Pomerania. Aortic diameter and AWT measurements were performed on a 1.5-T MRI scanner at the concentration of the right pulmonary artery displaying the ascending and the descending aorta. TSH, treated as continuous variable, was significantly associated with descending AWT (β = 0.11; 95 % confidence interval (CI) 0.02-0.21), while the association with ascending AWT was not statistically significant (β = 0.20; 95 % CI -0.01-0.21). High TSH (>3.29 mIU/L) was significantly associated with ascending (β = 0.12; 95 % CI 0.02-0.23) but not with descending AWT (β = 0.06; 95 % CI -0.04-0.16). There was no consistent association between TSH and aortic diameters. Our study demonstrated that AWT values increase with increasing serum TSH concentrations. Thus, a hypothyroid state may be indicative for aortic atherosclerosis. These results fit very well to the findings of previous studies pointing towards increased atherosclerotic risk in the hypothyroid state. • Serum TSH concentrations are positively associated with aortic wall thickness. • Serum TSH concentrations are not associated with the aortic diameters. • Serum 3,5-diiodothyronine concentrations may be positively associated with aortic wall thickness.

Improving the Efficiency of Abdominal Aortic Aneurysm Wall Stress Computations

PubMed Central

Zelaya, Jaime E.; Goenezen, Sevan; Dargon, Phong T.; Azarbal, Amir-Farzin; Rugonyi, Sandra

2014-01-01

An abdominal aortic aneurysm is a pathological dilation of the abdominal aorta, which carries a high mortality rate if ruptured. The most commonly used surrogate marker of rupture risk is the maximal transverse diameter of the aneurysm. More recent studies suggest that wall stress from models of patient-specific aneurysm geometries extracted, for instance, from computed tomography images may be a more accurate predictor of rupture risk and an important factor in AAA size progression. However, quantification of wall stress is typically computationally intensive and time-consuming, mainly due to the nonlinear mechanical behavior of the abdominal aortic aneurysm walls. These difficulties have limited the potential of computational models in clinical practice. To facilitate computation of wall stresses, we propose to use a linear approach that ensures equilibrium of wall stresses in the aneurysms. This proposed linear model approach is easy to implement and eliminates the burden of nonlinear computations. To assess the accuracy of our proposed approach to compute wall stresses, results from idealized and patient-specific model simulations were compared to those obtained using conventional approaches and to those of a hypothetical, reference abdominal aortic aneurysm model. For the reference model, wall mechanical properties and the initial unloaded and unstressed configuration were assumed to be known, and the resulting wall stresses were used as reference for comparison. Our proposed linear approach accurately approximates wall stresses for varying model geometries and wall material properties. Our findings suggest that the proposed linear approach could be used as an effective, efficient, easy-to-use clinical tool to estimate patient-specific wall stresses. PMID:25007052

Coarctation of the Aorta

MedlinePlus

... aorta may include: Narrowing of the aortic valve (aortic stenosis) High blood pressure Stroke Enlargement in a section of the wall of the aorta (aneurysm) Aortic rupture or tear (dissection) Premature coronary ...

Bioactive antibiotic levels in the human aorta.

PubMed

Mutch, D; Richards, G; Brown, R A; Mulder, D S

1982-12-01

A new bioassay was used to determine the level of active antibiotic within the aortic wall in 24 patients undergoing elective aortic surgery involving prosthetic grafts. The patients were divided into three groups and received either cefazolin, clindamycin, or cefoxitin intravenously at the induction of general anesthesia. Cefazolin and cefoxitin attained satisfactory tissue levels. Clindamycin did not reach therapeutic levels in the aortic wall. Blood levels did not correlate well with tissue levels.

Aortic iron overload with oxidative stress and inflammation in human and murine abdominal aortic aneurysm.

PubMed

Sawada, Hisashi; Hao, Hiroyuki; Naito, Yoshiro; Oboshi, Makiko; Hirotani, Shinichi; Mitsuno, Masataka; Miyamoto, Yuji; Hirota, Seiichi; Masuyama, Tohru

2015-06-01

Although iron is an essential element for maintaining physiological function, excess iron leads to tissue damage caused by oxidative stress and inflammation. Oxidative stress and inflammation play critical roles for the development of abdominal aortic aneurysm (AAA). However, it has not been investigated whether iron plays a role in AAA formation through oxidative stress and inflammation. We, therefore, examined whether iron is involved in the pathophysiology of AAA formation using human AAA walls and murine AAA models. Human aortic walls were collected from 53 patients who underwent cardiovascular surgery (non-AAA=34; AAA=19). Murine AAA was induced by infusion of angiotensin II to apolipoprotein E knockout mice. Iron was accumulated in human and murine AAA walls compared with non-AAA walls. Immunohistochemistry showed that both 8-hydroxy-2'-deoxyguanosine and CD68-positive areas were increased in AAA walls compared with non-AAA walls. The extent of iron accumulated area positively correlated with that of 8-hydroxy-2'-deoxyguanosine expression area and macrophage infiltration area in human and murine AAA walls. We next investigated the effects of dietary iron restriction on AAA formation in mice. Iron restriction reduced the incidence of AAA formation with attenuation of oxidative stress and inflammation. Aortic expression of transferrin receptor 1, intracellular iron transport protein, was increased in human and murine AAA walls, and transferrin receptor 1-positive area was similar to areas where iron accumulated and F4/80 were positive. Iron is involved in the pathophysiology of AAA formation with oxidative stress and inflammation. Dietary iron restriction could be a new therapeutic strategy for AAA progression. © 2015 American Heart Association, Inc.

Re-do aortic root replacement after an allograft aortic root replacement.

PubMed

Vrtik, Marian; Tesar, Peter J

2009-10-01

Structural degeneration of allograft aortic root is a global process. In addition to valvular degeneration, the allograft wall calcification poses a risk of systemic calcific embolization and late phase anastomotic aneurysm formation and rupture (anecdotal). Furthermore, the valve annulus is often small, and the tissues are rigid making the implantation of an adequately sized prosthesis within the allograft wall difficult. To avoid these issues, we routinely perform re-do aortic root replacement with either a mechanical valve conduit or bio-root composite graft. The technique has been successfully used in 22 consecutive patients with no operative mortality and minimal morbidity.

The influence of computational assumptions on analysing abdominal aortic aneurysm haemodynamics.

PubMed

Ene, Florentina; Delassus, Patrick; Morris, Liam

2014-08-01

The variation in computational assumptions for analysing abdominal aortic aneurysm haemodynamics can influence the desired output results and computational cost. Such assumptions for abdominal aortic aneurysm modelling include static/transient pressures, steady/transient flows and rigid/compliant walls. Six computational methods and these various assumptions were simulated and compared within a realistic abdominal aortic aneurysm model with and without intraluminal thrombus. A full transient fluid-structure interaction was required to analyse the flow patterns within the compliant abdominal aortic aneurysms models. Rigid wall computational fluid dynamics overestimates the velocity magnitude by as much as 40%-65% and the wall shear stress by 30%-50%. These differences were attributed to the deforming walls which reduced the outlet volumetric flow rate for the transient fluid-structure interaction during the majority of the systolic phase. Static finite element analysis accurately approximates the deformations and von Mises stresses when compared with transient fluid-structure interaction. Simplifying the modelling complexity reduces the computational cost significantly. In conclusion, the deformation and von Mises stress can be approximately found by static finite element analysis, while for compliant models a full transient fluid-structure interaction analysis is required for acquiring the fluid flow phenomenon. © IMechE 2014.

Aortic Valve Stenosis Alters Expression of Regional Aortic Wall Shear Stress: New Insights From a 4-Dimensional Flow Magnetic Resonance Imaging Study of 571 Subjects.

PubMed

van Ooij, Pim; Markl, Michael; Collins, Jeremy D; Carr, James C; Rigsby, Cynthia; Bonow, Robert O; Malaisrie, S Chris; McCarthy, Patrick M; Fedak, Paul W M; Barker, Alex J

2017-09-13

Wall shear stress (WSS) is a stimulus for vessel wall remodeling. Differences in ascending aorta (AAo) hemodynamics have been reported between bicuspid aortic valve (BAV) and tricuspid aortic valve patients with aortic dilatation, but the confounding impact of aortic valve stenosis (AS) is unknown. Five hundred seventy-one subjects underwent 4-dimensional flow magnetic resonance imaging in the thoracic aorta (210 right-left BAV cusp fusions, 60 right-noncoronary BAV cusp fusions, 245 tricuspid aortic valve patients with aortic dilatation, and 56 healthy controls). There were 166 of 515 (32%) patients with AS. WSS atlases were created to quantify group-specific WSS patterns in the AAo as a function of AS severity. In BAV patients without AS, the different cusp fusion phenotypes resulted in distinct differences in eccentric WSS elevation: right-left BAV patients exhibited increased WSS by 9% to 34% ( P <0.001) at the aortic root and along the entire outer curvature of the AAo whereas right-noncoronary BAV patients showed 30% WSS increase ( P <0.001) at the distal portion of the AAo. WSS in tricuspid aortic valve patients with aortic dilatation patients with no AS was significantly reduced by 21% to 33% ( P <0.01) in 4 of 6 AAo regions. In all patient groups, mild, moderate, and severe AS resulted in a marked increase in regional WSS ( P <0.001). Moderate-to-severe AS further increased WSS magnitude and variability in the AAo. Differences between valve phenotypes were no longer apparent. AS significantly alters aortic hemodynamics and WSS independent of aortic valve phenotype and over-rides previously described flow patterns associated with BAV and tricuspid aortic valve with aortic dilatation. Severity of AS must be considered when investigating valve-mediated aortopathy. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Locally Applied Leptin Induces Regional Aortic Wall Degeneration Preceding Aneurysm Formation in ApoE Deficient Mice

PubMed Central

Tao, Ming; Yu, Peng; Nguyen, Binh T.; Mizrahi, Boaz; Savion, Naphtali; Kolodgie, Frank D.; Virmani, Renu; Hao, Shuai; Ozaki, C. Keith; Schneiderman, Jacob

2013-01-01

Objective Leptin promotes atherosclerosis and vessel wall remodeling. As abdominal aorta aneurysm (AAA) formation involves tissue remodeling, we hypothesized that local leptin synthesis initiates and promotes this process. Methods and Results Human surgical AAA walls were analyzed for antigen and mRNA levels of leptin and leptin receptor (ObR), as well as mRNA for matrix metalloproteinases (MMP)-9, and MMP-12. Leptin and ObR antigen were evident in all AAAs, and, leptin, MMP-9, and MMP-12 mRNA was increased relative to age-matched non-dilated controls. To simulate in vivo local leptin synthesis, ApoE-/- mice were subjected to a para-visceral peri-aortic application of low-dose leptin. Leptin-treated aortas exhibited decreased TGFβ and increased MMP-9 mRNA levels 5 days after surgery, and ObR mRNA was up-regulated by day 28. Serial ultrasonography demonstrated accelerated regional aortic diameter growth after 28 days, correlating with local medial degeneration, increased MMP-9, MMP-12 and peri-adventitial macrophage clustering. Furthermore, the combination of local peri-aortic leptin and systemic angiotensin II administration augmented medial MMP-9 synthesis and aortic aneurysm size. Conclusions Leptin is locally synthesized in human AAA wall. Para-visceral aortic leptin in ApoE-/- mice induces local medial degeneration, and augments angiotensin II-induced AAA, thus suggesting novel mechanistic links between leptin and AAA formation. PMID:23220275

Resistance training improves aortic structure in Wistar rats.

PubMed

Souza, Romeu R; de França, Elias; Madureira, Diana; Pontes, Carla C R; Santana, Jeferson O; Caperuto, Erico C

Little information is available on the effects of resistance training on the aortic wall. This study aimed to quantify the effects of a resistance-training program on blood pressure and aortic wall structural components. Rats (aged three months) were randomized into sedentary group (control group, CG; n=10) or trained group (TG; n=10). The TG rats performed resistance training by climbing a 1.1-m vertical ladder (80° incline) five times a week for 12 weeks, and the CG remained sedentary. The rats were sacrificed and 5mm of the ascending aorta was submitted to histological sections, which were stained with hematoxylin-eosin, Picrosirius red, and Verhoeff's elastin, and used for morphometric studies. Left ventricle (LV) hypertrophy was determined by measuring LV wall thickness and LV internal diameter. The rats had similar repetition maximum before the resistance training. At the end of the resistance training period, the repetition maximum of the TG was 3.04-fold greater than the body weight. In the twelfth month, the left ventricular weight was 15.3% larger in the TG than in the CG, and the left ventricular internal diameter was reduced by 10% in the TG. Rats exposed to resistance training had a significant increase in aortic wall thickness, in both elastic lamina and collagen fibers, and in the thickness of collagen fibrils. Resistance training induces the development of concentric cardiac hypertrophy and improves the aortic wall components by producing a morphological expression pattern distinct from aortic pathological adaptation. Copyright © 2017. Publicado por Elsevier Editora Ltda.

Magnetic resonance imaging 4-D flow-based analysis of aortic hemodynamics in Turner syndrome.

PubMed

Arnold, Raoul; Neu, Marie; Hirtler, Daniel; Gimpel, Charlotte; Markl, Michael; Geiger, Julia

2017-04-01

Cardiovascular surveillance is important in Turner syndrome because of the increased risk of aortic dilation and dissection with consecutively increased mortality. To compare 4-D flow MRI for the characterization of aortic 3-D flow patterns, dimensions and vessel wall parameters in pediatric patients with Turner syndrome and age-matched controls. We performed 4-D flow MRI measuring in vivo 3-D blood flow with coverage of the thoracic aorta in 25 patients with Turner syndrome and in 16 female healthy controls (age mean ± standard deviation were 16 ± 5 years and 17 ± 4 years, respectively). Blood flow was visualized by time-resolved 3-D path lines. Visual grading of aortic flow in terms of helices and vortices was performed by two independent observers. Quantitative analysis included measurement of aortic diameters, quantification of peak systolic wall shear stress, pulsatility index and oscillatory shear index at eight defined sites. Patients with Turner syndrome had significantly larger aortic diameters normalized to BSA, increased vortices in the ascending aorta and elevated helix flow in the ascending and descending aorta compared to controls (all P<0.03). Patients with abnormal helical or vortical flow in the ascending aorta had significantly larger diameters of the ascending aorta (P<0.03). Peak systolic wall shear stress, pulsatility index and oscillatory shear index were significantly lower in Turner patients compared to controls (p=0.02, p=0.002 and p=0.01 respectively). Four-dimensional flow MRI provides new insights into the altered aortic hemodynamics and wall shear stress that could have an impact on the development of aortic dissections.

A novel sax-stent method in treatment of ascending aorta and aortic arch aneurysms evaluated by finite element simulations.

PubMed

Arokiaraj, M C; De Beule, M; De Santis, G

2017-02-01

A novel stent method to simplify treatment of proximal ascending aorta and aortic arch aneurysms was developed and investigated by finite element analysis. Therapy of ascending aortic and aortic arch aneurysms is difficult and challenging and is associated with various complications. A 55mm wide×120mm long stent was designed without the stent graft and the stent was deployed by an endovascular method in a virtual patient-specific aneurysm model. The stress-strain analysis and deployment characteristics were performed in a finite element analysis using the Abaqus software. The stent, when embedded in the aortic wall, significantly reduced aortic wall stresses, while preserving the side coronary ostia and side branches in the aortic arch. When tissue growth was modeled computationally over the stent struts the wall stresses in aorta was reduced. This effect became more pronounced when increasing the thickness of the tissue growth. There were no abnormal stresses in the aorta, coronary ostium and at the origin of aortic branches. The stent reduced aneurysm expansion cause by hypertensive condition from 2mm without stenting to 1.3mm after stenting and embedding. In summary, we uncovered a simple treatment method using a bare nitinol stent without stent graft in the treatment of the proximal aorta and aortic arch aneurysms, which could eventually replace the complex treatment methods for this disease. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

On the effect of computed tomography resolution to distinguish between abdominal aortic aneurysm wall tissue and calcification: A proof of concept.

PubMed

Barrett, H E; Cunnane, E M; O Brien, J M; Moloney, M A; Kavanagh, E G; Walsh, M T

2017-10-01

The purpose of this study is to determine the optimal target CT spatial resolution for accurately imaging abdominal aortic aneurysm (AAA) wall characteristics, distinguishing between tissue and calcification components, for an accurate assessment of rupture risk. Ruptured and non-ruptured AAA-wall samples were acquired from eight patients undergoing open surgical aneurysm repair upon institutional review board approval and informed consent was obtained from all patients. Physical measurements of AAA-wall cross-section were made using scanning electron microscopy. Samples were scanned using high resolution micro-CT scanning. A resolution range of 15.5-155μm was used to quantify the influence of decreasing resolution on wall area measurements, in terms of tissue and calcification. A statistical comparison between the reference resolution (15.5μm) and multi-detector CT resolution (744μm) was also made. Electron microscopy examination of ruptured AAAs revealed extremely thin outer tissue structure <200μm in radial distribution which is supporting the aneurysm wall along with large areas of adjacent medial calcifications far greater in area than the tissue layer. The spatial resolution of 155μm is a significant predictor of the reference AAA-wall tissue and calcification area measurements (r=0.850; p<0.001; r=0.999; p<0.001 respectively). The tissue and calcification area at 155μm is correct within 8.8%±1.86 and 26.13%±9.40 respectively with sensitivity of 87.17% when compared to the reference. The inclusion of AAA-wall measurements, through the use of high resolution-CT will elucidate the variations in AAA-wall tissue and calcification distributions across the wall which may help to leverage an improved assessment of AAA rupture risk. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of personalized external aortic root support on aortic root motion and distension in Marfan syndrome patients.

PubMed

Izgi, Cemil; Nyktari, Evangelia; Alpendurada, Francisco; Bruengger, Annina Studer; Pepper, John; Treasure, Tom; Mohiaddin, Raad

2015-10-15

Personalized external aortic root support (PEARS) is a novel surgical approach with the aim of stabilizing the aortic root size and decreasing risk of dissection in Marfan syndrome patients. A bespoke polymer mesh tailored to each patient's individual aorta shape is produced by modeling and then surgically implanted. The aim of this study is to assess the mechanical effects of PEARS on the aortic root systolic downward motion (an important determinant of aortic wall stress), aortic root distension and on the left ventricle (LV). A cohort of 27 Marfan patients had a prophylactic PEARS surgery between 2004 and 2012 with 24 having preoperative and follow-up cardiovascular magnetic resonance imaging studies. Systolic downward aortic root motion, aortic root distension, LV volumes/mass and mitral annular systolic excursion before the operation and in the latest follow-up were measured randomly and blinded. After a median follow-up of 50.5 (IQR 25.5-72) months following implantation of PEARS, systolic downward motion of aortic root was significantly decreased (12.6±3.6mm pre-operation vs 7.9±2.9mm latest follow-up, p<0.00001). There was a tendency for a decrease in systolic aortic root distension but this was not significant (median 4.5% vs 2%, p=0.35). There was no significant change in LV volumes, ejection fraction, mass and mitral annular systolic excursion in follow-up. PEARS surgery decreases systolic downward aortic root motion which is an important determinant of longitudinal aortic wall stress. Aortic wall distension and Windkessel function are not significantly impaired in the follow-up after implantation of the mesh which is also supported by the lack of deterioration of LV volumes or mass. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

Influence of aortic neck characteristics on successful aortic wall penetration of EndoAnchors in therapeutic use during endovascular aneurysm repair.

PubMed

Goudeketting, Seline R; van Noort, Kim; Ouriel, Kenneth; Jordan, William D; Panneton, Jean M; Slump, Cornelis H; de Vries, Jean-Paul P M

2018-04-21

This study sought to quantify EndoAnchor (Medtronic Vascular, Santa Rosa, Calif) penetration into the aortic wall in patients undergoing endovascular abdominal aortic aneurysm repair and to assess predictors of successful penetration and its relationship to postprocedural type IA endoleak. A subset of patients from the Aneurysm Treatment Using the Heli-FX Aortic Securement System Global Registry (ANCHOR) were included if they met the following criteria: the indication for EndoAnchor use was to treat a type IA endoleak, and postprocedure contrast-enhanced computed tomography (CT) scans of sufficient quality were available for core laboratory review. Patients undergoing implantation of cuffs or stents during the EndoAnchor implantation procedure were excluded. Baseline anatomic characteristics were recorded. The cohort was divided into patients with and without persistent type IA endoleaks at the first postoperative CT scan. Penetration of each EndoAnchor measured on this CT scan was defined as good penetration when the EndoAnchor penetrated ≥2 mm into the aortic wall, borderline penetration when EndoAnchor penetration was <2 mm or a gap remained between the endograft and aortic wall, or no penetration when the EndoAnchor did not penetrate into the aortic wall. Differences between the groups were analyzed with the Mann-Whitney U test or Fisher exact test. Multivariate analyses were performed to identify independent predictors of EndoAnchor penetration, and procedural success was defined by absence of type IA endoleak. Eighty-six patients of the primary (n = 61 [71%]) and revision (n = 25 [29%]) arms of the ANCHOR registry were included. There were 53 (62%) without and 33 (38%) with persistent type IA endoleaks on the first postprocedural CT scan. The median number of EndoAnchors with good penetration was significantly greater in the cohort without endoleaks, 4 (interquartile range, 3-5) vs 3 (interquartile range, 1.5-4), respectively (P = .002). A multivariate model for EndoAnchor penetration identified use of a Medtronic Endurant endograft as a factor associated with good penetration (P = .001), whereas poor penetration was associated with a larger aortic neck diameter 10 mm distal to the lowest renal artery (P < .001) and greater proximal neck calcium thickness (P = .004). EndoAnchor penetration was the only variable that attained significance (P < .001) in the multivariate model for successful treatment of a type IA endoleak. Adequate EndoAnchor penetration into the aortic wall is less likely when the aortic neck diameter is large or when the neck contains significant mural calcium. No penetration of the EndoAnchor was the only factor predictive of postprocedural type IA endoleak. This study stresses the importance of careful selection of patients based on preoperative assessment of the infrarenal neck on CT angiography and emphasizes careful deployment of EndoAnchors into the aortic wall to improve successful treatment of type IA endoleaks. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

The role of intraluminal thrombus on oxygen transport in abdominal aortic aneurysms

NASA Astrophysics Data System (ADS)

Madhavan, Sudharsan; Cherry Kemmerling, Erica

2017-11-01

Abdominal aortic aneurysm is ranked as the 13th leading cause of death in the United States. The presence of intraluminal thrombus is thought to cause hypoxia in the vessel wall eventually aggravating the condition. Our work investigates oxygen transport and consumption in a patient-specific model of an abdominal aortic aneurysm. The model includes intraluminal thrombus and consists of the abdominal aorta, renal arteries, and iliac arteries. Oxygen transport to and within the aortic wall layer was modeled, accounting for oxygen consumption and diffusion. Flow and transport in the lumen layer were modeled using coupled Navier-Stokes and scalar transport equations. The thrombus layer was assumed to be biomechanically inactive but permeable to oxygen transport in accordance with previously-measured diffusion coefficients. Plots of oxygen concentration through the layers illustrating reduced oxygen supply to the vessel walls in parts of the model that include thrombus will be presented.

Three-Channeled Aortic Dissection in a Patient without Marfan Syndrome

PubMed Central

Arita, Yoshie Inoue; Yamamoto, Takeshi; Hosokawa, Yusuke; Fujii, Masahiro; Nitta, Takashi; Shimizu, Wataru

2017-01-01

A 64-year-old man was admitted for evaluation of back pain. He did not have a Marfan syndrome (MFS)-like appearance, and had a history of a type B aortic dissection and total arch replacement. A connective tissue disorder had been suspected because of the histologic findings of the resected aortic wall. On admission, a computed tomography (CT) scan demonstrated a three-channeled aortic dissection (3ch-AD) measuring 63 mm in diameter. We planned to perform elective surgery during his hospitalization. On the fourth hospital day, he complained of severe back pain, and enhanced CT scan revealed an aortic rupture. The patients with 3ch-AD often have MFS. However, even if they do not have an MFS-like appearance, clinicians should consider fragility of the aortic wall in patients with 3ch-AD. If the aortic diameter is enlarged, early surgery is recommended. In particular, if a connective tissue disorder is obvious or suspected, emergent surgery is warranted. PMID:29187676

Elastin and collagen fibre microstructure of the human aorta in ageing and disease: a review

PubMed Central

Tsamis, Alkiviadis; Krawiec, Jeffrey T.; Vorp, David A.

2013-01-01

Aortic disease is a significant cause of death in developed countries. The most common forms of aortic disease are aneurysm, dissection, atherosclerotic occlusion and ageing-induced stiffening. The microstructure of the aortic tissue has been studied with great interest, because alteration of the quantity and/or architecture of the connective fibres (elastin and collagen) within the aortic wall, which directly imparts elasticity and strength, can lead to the mechanical and functional changes associated with these conditions. This review article summarizes the state of the art with respect to characterization of connective fibre microstructure in the wall of the human aorta in ageing and disease, with emphasis on the ascending thoracic aorta and abdominal aorta where the most common forms of aortic disease tend to occur. PMID:23536538

``Smart'' baroreception along the aortic arch, with reference to essential hypertension

NASA Astrophysics Data System (ADS)

Kember, G. C.; Zamir, M.; Armour, J. A.

2004-11-01

Beat-to-beat regulation of heart rate is dependent upon sensing of local stretching or local “disortion” by aortic baroreceptors. Distortions of the aortic wall are due mainly to left ventricular output and to reflected waves arising from the arterial tree. Distortions are generally believed to be useful in cardiac control since stretch receptors or aortic baroreceptors embedded in the adventitia of the aortic wall, transduce the distortions to cardiovascular neural reflex pathways responsible for beat-to-beat regulation of heart rate. Aortic neuroanatomy studies have also found a continuous strip of mechanosensory neurites spread along the aortic inner arch. Although their purpose is now unknown, such a combined sensing capacity would allow measurement of the space and time dependence of inner arch wall distortions due, among other things, to traveling waves associated with pulsatile flow in an elastic tube. We call this sensing capability-“smart baroreception.” In this paper we use an arterial tree model to show that the cumulative effects of wave reflections, from many sites far downstream, have a surprisingly pronounced effect on the pressure distribution in the root segment of the tree. By this mechanism global hemodynamics can be focused by wave reflections back to the aortic arch, where they can rapidly impact cardiac control via smart baroreception. Such sensing is likely important to maintain efficient heart function. However, alterations in the arterial tree due to aging and other natural processes can lead in such a system to altered cardiac control and essential hypertension.

A mechanistic model on the role of “radially-running” collagen fibers on dissection properties of human ascending thoracic aorta

PubMed Central

Pal, Siladitya; Tsamis, Alkiviadis; Pasta, Salvatore; D'Amore, Antonio; Gleason, Thomas G.; Vorp, David A.; Maiti, Spandan

2014-01-01

Aortic dissection (AoD) is a common condition that often leads to life-threatening cardiovaular emergency. From a biomechanics viewpoint, AoD involves failure of load-bearing microstructural components of the aortic wall, mainly elastin and collagen fibers. Delamination strength of the aortic wall depends on the load-bearing capacity and local micro-architecture of these fibers, which may vary with age, disease and aortic location. Therefore, quantifying the role of fiber micro-architecture on the delamination strength of the aortic wall may lead to improved understanding of AoD. We present an experimentally-driven modeling paradigm towards this goal. Specifically, we utilize collagen fiber microarchitecture, obtained in a parallel study from multi-photon microopy, in a predictive mechanistic framework to characterize the delamination strength. We then validate our model against peel test experiments on human aortic strips and utilize the model to predict the delamination strength of separate aortic strips and compare with experimental findings. We observe that the number density and failure energy of the radially-running collagen fibers control the peel strength. Furthermore, our model suggests that the lower delamination strength previously found for the circumferential direction in human aorta is related to a lower number density of radially-running collagen fibers in that direction. Our model sets the stage for an expanded future study that could predict AoD propagation in patient-specific aortic geometries and better understand factors that may influence propensity for occurrence. PMID:24484644

Impaired Vascular Contractility and Aortic Wall Degeneration in Fibulin-4 Deficient Mice: Effect of Angiotensin II Type 1 (AT1) Receptor Blockade

PubMed Central

Moltzer, Els; te Riet, Luuk; Swagemakers, Sigrid M. A.; van Heijningen, Paula M.; Vermeij, Marcel; van Veghel, Richard; Bouhuizen, Angelique M.; van Esch, Joep H. M.; Lankhorst, Stephanie; Ramnath, Natasja W. M.; de Waard, Monique C.; Duncker, Dirk J.; van der Spek, Peter J.; Rouwet, Ellen V.; Danser, A. H. Jan; Essers, Jeroen

2011-01-01

Medial degeneration is a key feature of aneurysm disease and aortic dissection. In a murine aneurysm model we investigated the structural and functional characteristics of aortic wall degeneration in adult fibulin-4 deficient mice and the potential therapeutic role of the angiotensin (Ang) II type 1 (AT1) receptor antagonist losartan in preventing aortic media degeneration. Adult mice with 2-fold (heterozygous Fibulin-4+/R) and 4-fold (homozygous Fibulin-4R/R) reduced expression of fibulin-4 displayed the histological features of cystic media degeneration as found in patients with aneurysm or dissection, including elastin fiber fragmentation, loss of smooth muscle cells, and deposition of ground substance in the extracellular matrix of the aortic media. The aortic contractile capacity, determined by isometric force measurements, was diminished, and was associated with dysregulation of contractile genes as shown by aortic transcriptome analysis. These structural and functional alterations were accompanied by upregulation of TGF-β signaling in aortas from fibulin-4 deficient mice, as identified by genome-scaled network analysis as well as by immunohistochemical staining for phosphorylated Smad2, an intracellular mediator of TGF-β. Tissue levels of Ang II, a regulator of TGF-β signaling, were increased. Prenatal treatment with the AT1 receptor antagonist losartan, which blunts TGF-β signaling, prevented elastic fiber fragmentation in the aortic media of newborn Fibulin-4R/R mice. Postnatal losartan treatment reduced haemodynamic stress and improved lifespan of homozygous knockdown fibulin-4 animals, but did not affect aortic vessel wall structure. In conclusion, the AT1 receptor blocker losartan can prevent aortic media degeneration in a non-Marfan syndrome aneurysm mouse model. In established aortic aneurysms, losartan does not affect aortic architecture, but does improve survival. These findings may extend the potential therapeutic application of inhibitors of the renin-angiotensin system to the preventive treatment of aneurysm disease. PMID:21858106

Tissue Doppler Imaging in the evaluation of abdominal aortic pulsatility: a useful tool for the neonatologist.

PubMed

Valerio, Enrico; Grison, Alessandra; Capretta, Anna; Golin, Rosanna; Ferrarese, Paola; Bellettato, Massimo

2017-03-01

Sonographic cardiac evaluation of newborns with suspected aortic coarctation (AoC) should tend to demonstrate a good phasic and pulsatile flow and the absence of pressure gradient along a normally conformed aortic arch from the modified left parasternal and suprasternal echocardiographic views; these findings, however, may not necessarily rule out a more distal coarctation in the descending aorta. For this reason, the sonographic exam of newborns with suspected AoC should always include a Doppler evaluation of abdominal aortic blood flow from the subcostal view. Occasionally, however, a clearly pulsatile Doppler flow trace in abdominal aorta may be difficult to obtain due to the bad insonation angle existing between the probe and the vessel. In such suboptimal ultrasonic alignment situation, the use of Tissue Doppler Imaging instead of classic Doppler flow imaging may reveal a preserved aortic pulsatility by sampling the aortic wall motion induced by normal flow. We propose to take advantage of the TDI pattern as a surrogate of a normal pulsatile Doppler flow trace in abdominal aorta when the latter is difficult to obtain due to malalignment with the insonated vessel.

Quantitative expression and localization of cysteine and aspartic proteases in human abdominal aortic aneurysms

PubMed Central

Lohoefer, Fabian; Reeps, Christian; Lipp, Christina; Rudelius, Martina; Haertl, Felix; Matevossian, Edouard; Zernecke, Alma; Eckstein, Hans-Henning; Pelisek, Jaroslav

2014-01-01

Cysteine and aspartic proteases possess high elastolytic activity and might contribute to the degradation of the abdominal aortic aneurysm (AAA) wall. The aim of this study was to analyze, in detail, the proteases (cathepsins B, D, K, L and S, and inhibitor cystatin C) found in human AAA and healthy aortic tissue samples. The vessel walls from AAA patients (n=36) and nonaneurysmal aortae (n=10) were retrieved using conventional surgical repair and autopsy methods. Serum samples from the same AAA patients and 10 healthy volunteers were also collected. Quantitative expression analyses were performed at the mRNA level using real-time reverse transcriptase-PCR (RT–PCR). Furthermore, analyses at the protein level included western blot and immunoprecipitation analyses. Cellular sources of cysteine/aspartic proteases and cystatin C were identified by immunohistochemistry (IHC). All cysteine/aspartic proteases and cystatin C were detected in the AAA and control samples. Using quantitative RT–PCR, a significant increase in expression was observed for cathepsins B (P=0.021) and L (P=0.018), compared with the controls. Cathepsin B and cystatin C were also detected in the serum of AAA patients. Using IHC, smooth muscle cells (SMCs) and macrophages were positive for all of the tested cathepsins, as well as cystatin C; in addition, the lymphocytes were mainly positive for cathepsin B, followed by cathepsins D and S. All cysteine/aspartic proteases analyzed in our study were detected in the AAA and healthy aorta. The highest expression was found in macrophages and SMCs. Consequently, cysteine/aspartic proteases might play a substantial role in AAA. PMID:24833013

Differential transesophageal echocardiographic diagnosis between linear artifacts and intraluminal flap of aortic dissection or disruption.

PubMed

Vignon, P; Spencer, K T; Rambaud, G; Preux, P M; Krauss, D; Balasia, B; Lang, R M

2001-06-01

The relatively low specificity of transesophageal echocardiography (TEE) for the diagnosis of aortic dissection (AD) or traumatic disruption of the aorta (TDA) has been attributed to linear artifacts. We sought to determine the incidence of intra-aortic linear artifacts in a cohort of patients with suspected AD or TDA, to establish the differential TEE diagnostic criteria between these artifacts and true aortic flaps, and to evaluate their impact on TEE diagnostic accuracy. During an 8-year period, patients at high risk of AD (n = 261) or TDA (n = 90) who underwent a TEE study and had confirmed final diagnoses were studied. In an initial retrospective series, linear artifacts were observed within the ascending and descending aorta in 59 of 230 patients (26%) and 17 of 230 patients (7%), respectively. TEE findings associated with linear artifacts in the ascending aorta were as follows: displacement parallel to aortic walls; similar blood flow velocities on both sides; angle with the aortic wall > 85 degrees; and thickness > 2.5 mm. Diagnostic criteria of reverberant images in the descending aorta were as follows: displacement parallel to aortic walls, overimposition of blood flow, and similar blood flow velocities on both sides of the image. In a subsequent prospective series (n = 121), systematic use of these diagnostic criteria resulted in improved TEE specificity for the identification of true intra-aortic flaps. Misleading intra-aortic linear artifacts are frequently observed in patients undergoing a TEE study for suspected AD or TDA. Routine use of the herein-proposed diagnostic criteria promises to further improve TEE diagnostic accuracy in the setting of severely ill patients with potential need for prompt surgery.

Properties of calcium-containing microparticles formed in the process of biomineralization of the human aortic wall

NASA Astrophysics Data System (ADS)

Zlatoustova, O. Yu; Vasilev, S. V.; Rudy, A. S.

2016-08-01

The results of the study of human aortic walls, subjected to different stages of mineralization are presented. By means of scanning electron microscopy and X-ray microanalysis the morphology, elemental composition and characteristics of the mineral component localization were investigated. The key differences in the initial, intermediate and final stages of pathological mineralization of the aorta wall were identified. The data obtained may be useful in describing the mechanism of biomineral deposits formation in human body.

The impact of personalized probabilistic wall thickness models on peak wall stress in abdominal aortic aneurysms.

PubMed

Biehler, J; Wall, W A

2018-02-01

If computational models are ever to be used in high-stakes decision making in clinical practice, the use of personalized models and predictive simulation techniques is a must. This entails rigorous quantification of uncertainties as well as harnessing available patient-specific data to the greatest extent possible. Although researchers are beginning to realize that taking uncertainty in model input parameters into account is a necessity, the predominantly used probabilistic description for these uncertain parameters is based on elementary random variable models. In this work, we set out for a comparison of different probabilistic models for uncertain input parameters using the example of an uncertain wall thickness in finite element models of abdominal aortic aneurysms. We provide the first comparison between a random variable and a random field model for the aortic wall and investigate the impact on the probability distribution of the computed peak wall stress. Moreover, we show that the uncertainty about the prevailing peak wall stress can be reduced if noninvasively available, patient-specific data are harnessed for the construction of the probabilistic wall thickness model. Copyright © 2017 John Wiley & Sons, Ltd.

Locally applied leptin induces regional aortic wall degeneration preceding aneurysm formation in apolipoprotein E-deficient mice.

PubMed

Tao, Ming; Yu, Peng; Nguyen, Binh T; Mizrahi, Boaz; Savion, Naphtali; Kolodgie, Frank D; Virmani, Renu; Hao, Shuai; Ozaki, C Keith; Schneiderman, Jacob

2013-02-01

Leptin promotes atherosclerosis and vessel wall remodeling. As abdominal aortic aneurysm (AAA) formation involves tissue remodeling, we hypothesized that local leptin synthesis initiates and promotes this process. Human surgical AAA walls were analyzed for antigen and mRNA levels of leptin and leptin receptor, as well as mRNA for matrix metalloproteinases (MMP)-9 and MMP-12. Leptin and leptin receptor antigen were evident in all AAAs, and leptin, MMP-9, and MMP-12 mRNA was increased relative to age-matched nondilated controls. To simulate in vivo local leptin synthesis, ApoE(-/-) mice were subjected to a paravisceral periaortic application of low-dose leptin. Leptin-treated aortas exhibited decreased transforming growth factor-β and increased MMP-9 mRNA levels 5 days after surgery, and leptin receptor mRNA was upregulated by day 28. Serial ultrasonography demonstrated accelerated regional aortic diameter growth after 28 days, correlating with local medial degeneration, increased MMP-9, MMP-12, and periadventitial macrophage clustering. Furthermore, the combination of local periaortic leptin and systemic angiotensin II administration augmented medial MMP-9 synthesis and aortic aneurysm size. Leptin is locally synthesized in human AAA wall. Paravisceral aortic leptin in ApoE(-/-) mice induces local medial degeneration and augments angiotensin II-induced AAA, thus suggesting novel mechanistic links between leptin and AAA formation.

Blood flow characteristics in the ascending aorta after TAVI compared to surgical aortic valve replacement.

PubMed

Trauzeddel, Ralf Felix; Löbe, Ulrike; Barker, Alex J; Gelsinger, Carmen; Butter, Christian; Markl, Michael; Schulz-Menger, Jeanette; von Knobelsdorff-Brenkenhoff, Florian

2016-03-01

Ascending aortic blood flow characteristics are altered after aortic valve surgery, but the effect of transcatheter aortic valve implantation (TAVI) is unknown. Abnormal flow may be associated with aortic and cardiac remodeling. We analyzed blood flow characteristics in the ascending aorta after TAVI in comparison to conventional stented aortic bioprostheses (AVR) and healthy subjects using time-resolved three-dimensional flow-sensitive cardiovascular magnetic resonance imaging (4D-flow MRI). Seventeen patients with TAVI (Edwards Sapien XT), 12 with AVR and 9 healthy controls underwent 4D-flow MRI of the ascending aorta. Target parameters were: severity of vortical and helical flow pattern (semiquantitative grading from 0 = none to 3 = severe) and the local distribution of systolic wall shear stress (WSSsystole). AVR revealed significantly more extensive vortical and helical flow pattern than TAVI (p = 0.042 and p = 0.002) and controls (p < 0.001 and p = 0.001). TAVI showed significantly more extensive vortical flow than controls (p < 0.001). Both TAVI and AVR revealed marked blood flow eccentricity (64.7 and 66.7%, respectively), whereas controls showed central blood flow (88.9%). TAVI and AVR exhibited an asymmetric distribution of WSSsystole in the mid-ascending aorta with local maxima at the right anterior aortic wall and local minima at the left posterior wall. In contrast, controls showed a symmetric distribution of WSSsystole along the aortic circumference. Blood flow was significantly altered in the ascending aorta after TAVI and AVR. Changes were similar regarding WSSsystole distribution, while TAVI resulted in less helical and vortical blood flow.

Ferroelectricity and piezoelectricity in soft biological tissue: Porcine aortic walls revisited

NASA Astrophysics Data System (ADS)

Lenz, Thomas; Hummel, Regina; Katsouras, Ilias; Groen, Wilhelm A.; Nijemeisland, Marlies; Ruemmler, Robert; Schäfer, Michael K. E.; de Leeuw, Dago M.

2017-09-01

Recently reported piezoresponse force microscopy (PFM) measurements have proposed that porcine aortic walls are ferroelectric. This finding may have great implications for understanding biophysical properties of cardiovascular diseases such as arteriosclerosis. However, the complex anatomical structure of the aortic wall with different extracellular matrices appears unlikely to be ferroelectric. The reason is that a prerequisite for ferroelectricity, which is the spontaneous switching of the polarization, is a polar crystal structure of the material. Although the PFM measurements were performed locally, the phase-voltage hysteresis loops could be reproduced at different positions on the tissue, suggesting that the whole aorta is ferroelectric. To corroborate this hypothesis, we analyzed entire pieces of porcine aorta globally, both with electrical and electromechanical measurements. We show that there is no hysteresis in the electric displacement as well as in the longitudinal strain as a function of applied electric field and that the strain depends on the electric field squared. By using the experimentally determined quasi-static permittivity and Young's modulus of the fixated aorta, we show that the strain can quantitatively be explained by Maxwell stress and electrostriction, meaning that the aortic wall is neither piezoelectric nor ferroelectric, but behaves as a regular dielectric material.

Obtaining the biomechanical behavior of ascending aortic aneurysm via the use of novel speckle tracking echocardiography.

PubMed

Alreshidan, Mohammed; Shahmansouri, Nastaran; Chung, Jennifer; Lash, Vynka; Emmott, Alexander; Leask, Richard L; Lachapelle, Kevin

2017-04-01

Ex vivo measurement of ascending aortic biomechanical properties may help understand the risk for rupture or dissection of dilated ascending aortas. A validated in vivo method that can predict aortic biomechanics does not exist. Speckle tracking transesophageal echocardiography (TEE) has been used to measure ventricular stiffness; we sought to determine whether speckle TEE could be adapted to estimate aortic stiffness in vivo and compare these findings with those obtained by ex vivo tissue measurements. A total of 17 patients undergoing ascending aortic resection were recruited to with a mean aortic diameter was 56.16 ± 15 mm. Intraoperative speckle TEE tracking analysis was used to calculate aortic stiffness index using the following equation: β2=ln(SBP/DBP)/AoS, where β2 is the stiffness index; SBP is systolic blood pressure; DBP is diastolic blood pressure; and AoS is the circumferential strain. Ex vivo stiffness was obtained by mechanical tissue testing according to previously described methods. The aortic ring at the pulmonary trunk was divided into 4 equal quadrants. The in vivo stiffness index for the inner curvature, anterior wall, outer curvature, and posterior wall were 0.0544 ± 0.0490, 0.0295 ± 0.0199, 0.0411 ± 0.0328, and 0.0502 ± 0.0320, respectively. The mean ex vivo 25% apparent stiffness for inner curvature, anterior wall, outer curvature, and posterior wall were 0.0616 ± 0.0758 MPa, 0.0352 ± 0.00992 MPa, 0.0405 ± 0.0199 MPa, and 0.0327 ± 0.0106 MPa, respectively. The patient-matched ex vivo 25% apparent stiffness and in vivo stiffness index were not significantly different (P = .8617, 2-way analysis of variance with repeated measures). The use of speckle TEE appears to be a promising technique to estimate ex vivo mechanical properties of the ascending aortic tissue. Copyright © 2016 The American Association for Thoracic Surgery. All rights reserved.

Ex vivo blood vessel bioreactor for analysis of the biodegradation of magnesium stent models with and without vessel wall integration

PubMed Central

Wang, Juan; Liu, Lumei; Wu, Yifan; Maitz, Manfred F.; Wang, Zhihong; Koo, Youngmi; Zhao, Ansha; Sankar, Jagannathan; Kong, Deling; Huang, Nan; Yun, Yeoheung

2017-01-01

Current in vitro models fail in predicting the degradation rate and mode of magnesium (Mg) stents in vivo. To overcome this, the microenvironment of the stent is simulated here in an ex vivo bioreactor with porcine aorta and circulating medium, and compared with standard static in vitro immersion and with in vivo rat aorta models. In ex vivo and in vivo conditions, pure Mg wires were exposed to the aortic lumen and inserted into the aortic wall to mimic early- and long-term implantation, respectively. Results showed that: 1) Degradation rates of Mg were similar for all the fluid diffusion conditions (in vitro static, aortic wall ex vivo and in vivo); however, Mg degradation under flow condition (i.e. in the lumen) in vivo was slower than ex vivo; 2) The corrosion mode in the samples can be mainly described as localized (in vitro), mixed localized and uniform (ex vivo), and uniform (in vivo); 3) Abundant degradation products (MgO/Mg(OH)2 and Ca/P) with gas bubbles accumulated around the localized degradation regions ex vivo, but a uniform and thin degradation product layer was found in vivo. It is concluded that the ex vivo vascular bioreactor provides an improved test setting for magnesium degradation between static immersion and animal experiments and highlights its promising role in bridging degradation behavior and biological response for vascular stent research. PMID:28013101

Haemodynamical stress in mouse aortic arch with atherosclerotic plaques: Preliminary study of plaque progression

PubMed Central

Assemat, P.; Siu, K.K.; Armitage, J.A.; Hokke, S.N.; Dart, A.; Chin-Dusting, J.; Hourigan, K.

2014-01-01

Atherosclerotic plaques develop at particular sites in the arterial tree, and this regional localisation depends largely on haemodynamic parameters (such as wall shear stress; WSS) as described in the literature. Plaque rupture can result in heart attack or stroke and hence understanding the development and vulnerability of atherosclerotic plaques is critically important. The purpose of this study is to characterise the haemodynamics of blood flow in the mouse aortic arch using numerical modelling. The geometries are digitalised from synchrotron imaging and realistic pulsatile blood flow is considered under rigid wall assumptions. Two cases are considered; arteries with and without plaque. Mice that are fed under fat diet present plaques in the aortic arch whose size is dependent on the number of weeks under the diet. The plaque distribution in the region is however relatively constant through the different samples. This result underlines the influence of the geometry and consequently of the wall shear stresses for plaque formation with plaques growing in region of relative low shear stresses. A discussion of the flow field in real geometry in the presence and absence of plaques is conducted. The presence of plaques was shown to alter the blood flow and hence WSS distribution, with regions of localised high WSS, mainly on the wall of the brachiocephalic artery where luminal narrowing is most pronounced. In addition, arch plaques are shown to induce recirculation in the blood flow, a phenomenon with potential influence on the progression of the plaques. The oscillatory shear index and the relative residence time have been calculated on the geometry with plaques to show the presence of this recirculation in the arch, an approach that may be useful for future studies on plaque progression. PMID:25349678

[A study on residual strain of abdominal aortic aneurysm after intraperitoneal administration of saturated hydrogen saline in rats].

PubMed

Song, Yuxiang; Chen, Feng; Xiong, Jiang; Guo, Wei; Pan, Xiujie; Jia, Senhao; Liu, Jie

2013-07-01

By observation of the diameter, progression rate, wall thickness, and the opening angle of the abnormal aortic of abdominal aortic aneurysm (AAA) in rats, to observe the effect of saturated hydrogen saline on residual strain of AAA rats, and to investigate its inhibition effect on AAA formation. Twenty healthy male Sprague Dawley rats (weighing, 200-220 g) were randomly divided into 2 groups, which was made the AAA model by infiltration of the abdominal arota with 0.5 mol/L calcium chloride. Saturated hydrogen saline (5 mL/kg) or saline (5 mL/kg) was injected intraperitoneally in the experimental group or control group respectively, every day for 28 days. At 28 days, the diameter, progression rate, wall thickness, and opening angle of the abnormal aorta were mearsured. The aortic tissue was harvested for histological examination (HE staining and aldehyde-fuchsin staining). At 28 days after operation, the diameter of abnormal aorta in 2 groups were significantly higher than preoperative ones (P < 0.05), the progression rate in experimental group (65% +/- 15%) was significantly lower than that in control group (128% +/- 54%) (t=3.611, P=0.005). The opening angle and the wall thickness in experimental group were (88.78 +/- 29.20) degrees and (0.14 +/- 0.03) mm respectively, had significant differences when compared with the values in control group [(44.23 +/- 28.52) degrees and (0.36 +/- 0.05) mm respectively] (P < 0.01). The integrity and continuity of the aortic wall in experimental group were superior to that in the control group. Compared with the control group, the injury of elastic fiber in aortic wall and the infiltration of inflammation were all reduced. Saturated hydrogen saline can maintain good mechanical properties and reduce dilatation of the aorta by increasing residual strain and reducing the remodeling of it.

Accelerated aortic imaging using small field of view imaging and electrocardiogram-triggered quadruple inversion recovery magnetization preparation.

PubMed

Peel, Sarah A; Hussain, Tarique; Cecelja, Marina; Abbas, Abeera; Greil, Gerald F; Chowienczyk, Philip; Spector, Tim; Smith, Alberto; Waltham, Matthew; Botnar, Rene M

2011-11-01

To accelerate and optimize black blood properties of the quadruple inversion recovery (QIR) technique for imaging the abdominal aortic wall. QIR inversion delays were optimized for different heart rates in simulations and phantom studies by minimizing the steady state magnetization of blood for T(1) = 100-1400 ms. To accelerate and improve black blood properties of aortic vessel wall imaging, the QIR prepulse was combined with zoom imaging and (a) "traditional" and (b) "trailing" electrocardiogram (ECG) triggering. Ten volunteers were imaged pre- and post-contrast administration using a conventional ECG-triggered double inversion recovery (DIR) and the two QIR implementations in combination with a zoom-TSE readout. The QIR implemented with "trailing" ECG-triggering resulted in consistently good blood suppression as the second inversion delay was timed during maximum systolic flow in the aorta. The blood signal-to-noise ratio and vessel wall to blood contrast-to-noise ratio, vessel wall sharpness, and image quality scores showed a statistically significant improvement compared with the traditional QIR implementation with and without ECG-triggering. We demonstrate that aortic vessel wall imaging can be accelerated with zoom imaging and that "trailing" ECG-triggering improves black blood properties of the aorta which is subject to motion and variable blood flow during the cardiac cycle. Copyright © 2011 Wiley Periodicals, Inc.

Mild aerobic exercise blocks elastin fiber fragmentation and aortic dilatation in a mouse model of Marfan syndrome associated aortic aneurysm.

PubMed

Gibson, Christine; Nielsen, Cory; Alex, Ramona; Cooper, Kimbal; Farney, Michael; Gaufin, Douglas; Cui, Jason Z; van Breemen, Cornelis; Broderick, Tom L; Vallejo-Elias, Johana; Esfandiarei, Mitra

2017-07-01

Regular low-impact physical activity is generally allowed in patients with Marfan syndrome, a connective tissue disorder caused by heterozygous mutations in the fibrillin-1 gene. However, being above average in height encourages young adults with this syndrome to engage in high-intensity contact sports, which unfortunately increases the risk for aortic aneurysm and rupture, the leading cause of death in Marfan syndrome. In this study, we investigated the effects of voluntary (cage-wheel) or forced (treadmill) aerobic exercise at different intensities on aortic function and structure in a mouse model of Marfan syndrome. Four-week-old Marfan and wild-type mice were subjected to voluntary and forced exercise regimens or sedentary lifestyle for 5 mo. Thoracic aortic tissue was isolated and subjected to structural and functional studies. Our data showed that exercise improved aortic wall structure and function in Marfan mice and that the beneficial effect was biphasic, with an optimum at low intensity exercise (55-65% V̇o 2max ) and tapering off at a higher intensity of exercise (85% V̇o 2max ). The mechanism underlying the reduced elastin fragmentation in Marfan mice involved reduction of the expression of matrix metalloproteinases 2 and 9 within the aortic wall. These findings present the first evidence of potential beneficial effects of mild exercise on the structural integrity of the aortic wall in Marfan syndrome associated aneurysm. Our finding that moderate, but not strenuous, exercise protects aortic structure and function in a mouse model of Marfan syndrome could have important implications for the medical care of young Marfan patients. NEW & NOTEWORTHY The present study provides conclusive scientific evidence that daily exercise can improve aortic health in a mouse model of Marfan syndrome associated aortic aneurysm, and it establishes the threshold for the exercise intensity beyond which exercise may not be as protective. These findings establish a platform for a new focus on promoting regular exercise in Marfan patients at an optimum intensity and create a paradigm shift in clinical care of Marfan patients suffering from aortic aneurysm complications. Copyright © 2017 the American Physiological Society.

Minimally Invasive Aortic Valve Replacement Following Root Enlargement on too Narrow Annulus to Perform Transcatheter Aortic Valve Implantation.

PubMed

Sakamoto, Kosuke; Totsugawa, Toshinori; Hiraoka, Arudo; Tamura, Kentaro; Yoshitaka, Hidenori; Sakaguchi, Taichi

2018-05-30

An 88-year-old woman was diagnosed with aortic stenosis and an aortic annulus that was too narrow to perform transcatheter aortic valve implantation. Surgery was performed through a 7-cm right mini-thoracotomy at the fourth intercostal space. A 19-mm aortic valve bioprosthesis was implanted after root enlargement. The fourth intercostal space was a suitable site for aortic root enlargement because of the shorter skin-to-root distance and the detailed exposure of the aortic valve after cutting the aortic wall. This study concluded that minimally-invasive aortic valve replacement following root enlargement can be an option for the treatment of elderly patients with aortic stenosis accompanied by an annulus that is too small to perform transcatheter aortic valve implantation.

Haemodynamic predictors of a penetrating atherosclerotic ulcer rupture using fluid–structure interaction analysis

PubMed Central

D'Ancona, Giuseppe; Amaducci, Andrea; Rinaudo, Antonino; Pasta, Salvatore; Follis, Fabrizio; Pilato, Michele; Baglini, Roberto

2013-01-01

We present preliminary data on the flow-induced haemodynamic and structural loads exerted on a penetrating atherosclerotic aortic ulcer (PAU). Specifically, one-way fluid–structure interaction analysis was performed on the aortic model reconstructed from a 66-year-old male patient with a PAU that evolved into an intramural haematoma and rupture of the thoracic aorta. The results show that elevated blood pressure (117 mmHg) and low flow velocity at the aortic wall (0.15 m/s2) occurred in the region of the PAU. We also found a low value of time-averaged wall shear stress (1.24 N/m2) and a high value of the temporal oscillation in the wall shear stress (oscillatory shear index = 0.13) in the region of the PAU. After endovascular treatment, these haemodynamic parameters were distributed uniformly on the luminal surface of the stent graft. These findings suggest that wall shear stress could be considered one of the major haemodynamic factors indicating the structural fragility of the PAU wall, which ultimately lead to PAU growth and rupture. PMID:23736658

Left Ventricular Free Wall Rupture in Acute Myocardial Infarction

PubMed Central

Amir, Offer; Smith, Ronald; Nishikawa, Akaira; Gregoric, Igor D.; Smart, Frank W.

2005-01-01

We describe a case of subacute left ventricular free wall rupture during acute myocardial infarction in a 68-year-old man. The diagnosis was confirmed by echocardiography. The patient was supported by an intra-aortic balloon pump until the ruptured wall could be successfully repaired by suturing and gluing a pericardial patch over the defect and bypassing the left anterior descending coronary artery with a vein graft. This case demonstrates that left ventricular free wall rupture is not always fatal and that early diagnosis and institution of intra-aortic balloon pump support in such patients can allow successful bridging to definitive emergency surgical therapy. PMID:16392235

Determinants of elevated pulse pressure in middle-aged and older subjects with uncomplicated systolic hypertension: the role of proximal aortic diameter and the aortic pressure-flow relationship.

PubMed

Mitchell, Gary F; Lacourcière, Yves; Ouellet, Jean-Pascal; Izzo, Joseph L; Neutel, Joel; Kerwin, Linda J; Block, Alan J; Pfeffer, Marc A

2003-09-30

Elevated pulse pressure (PP) is associated with increased cardiovascular risk and is thought to be secondary to elastin fragmentation with secondary collagen deposition and stiffening of the aortic wall, leading to a dilated, noncompliant vasculature. By use of calibrated tonometry and pulsed Doppler, arterial stiffness and pulsatile hemodynamics were assessed in 128 subjects with uncomplicated systolic hypertension (supine systolic pressure > or =140 mm Hg off medication) and 30 normotensive control subjects of comparable age and gender. Pulse-wave velocity was assessed from tonometry and body surface measurements. Characteristic impedance (Zc) was calculated from the ratio of change in carotid pressure and aortic flow in early systole. Effective aortic diameter was assessed by use of the water hammer equation. Hypertensives were heavier (P<0.001) and had higher PP (P<0.001), which was attributable primarily to higher Zc (P<0.001), especially in women. Pulse-wave velocity was higher in hypertensives (P=0.001); however, this difference was not significant after adjustment for differences in mean arterial pressure (MAP) (P>0.153), whereas increased Zc remained highly significant (P<0.001). Increased Zc in women and in hypertensive men was attributable to decreased effective aortic diameter, with no difference in wall stiffness at comparable MAP and body weight. Elevated PP in systolic hypertension was independent of MAP and was attributable primarily to elevated Zc and reduced effective diameter of the proximal aorta. These findings are not consistent with the hypothesis of secondary aortic degeneration, dilation, and wall stiffening but rather suggest that aortic function may play an active role in the pathophysiology of systolic hypertension.

In vivo assessment of aortic aneurysm wall integrity using elastin-specific molecular magnetic resonance imaging.

PubMed

Botnar, René M; Wiethoff, Andrea J; Ebersberger, Ullrich; Lacerda, Sara; Blume, Ulrike; Warley, Alice; Jansen, Christian H P; Onthank, David C; Cesati, Richard R; Razavi, Reza; Marber, Michael S; Hamm, Bernd; Schaeffter, Tobias; Robinson, Simon P; Makowski, Marcus R

2014-07-01

The incidence of abdominal aortic aneurysms (AAAs) has increased during the last decades. However, there is still controversy about the management of medium-sized AAAs. Therefore, novel biomarkers, besides aneurysmal diameter, are needed to assess aortic wall integrity and risk of rupture. Elastin is the key protein for maintaining aortic wall tensile strength and stability. The progressive breakdown of structural proteins, in particular, medial elastin, is responsible for the inability of the aortic wall to withstand intraluminal hemodynamic forces. Here, we evaluate the usefulness of elastin-specific molecular MRI for the in vivo characterization of AAAs. To induce AAAs, ApoE(-/-) mice were infused with angiotensin-II. An elastin-specific magnetic resonance molecular imaging agent (ESMA) was administered after 1, 2, 3, and 4 weeks of angiotensin-II infusion to assess elastin composition of the aorta (n=8 per group). The high signal provided by ESMA allowed for imaging with high spatial resolution, resulting in an accurate assessment of ruptured elastic laminae and the compensatory expression of elastic fibers. In vivo contrast-to-noise ratios and R1-relaxation rates after ESMA administration were in good agreement with ex vivo histomorphometry (Elastica van Gieson stain) and gadolinium concentrations determined by inductively coupled plasma mass spectroscopy. Electron microscopy confirmed colocalization of ESMA with elastic fibers. Changes in elastin content could be readily delineated and quantified at different stages of AAAs by elastin-specific molecular magnetic resonance imaging. ESMA-MRI offers potential for the noninvasive detection of the aortic rupture site prior to dilation of the aorta and the subsequent in vivo monitoring of compensatory repair processes during the progression of AAAs. © 2014 American Heart Association, Inc.

Impact of magnesium:calcium ratio on calcification of the aortic wall.

PubMed

Villa-Bellosta, Ricardo

2017-01-01

An inverse relationship between serum magnesium concentration and vascular calcification has been reported following observational clinical studies. Moreover, several studies have been suggesting a protective effect of magnesium on the vascular calcification. However, the exact mechanism remains elusive, and investigators have speculated among a myriad of potential actions. The effect of magnesium on calcification of the aortic wall is yet to be investigated. In the present study, the effects of magnesium and calcium on the metabolism of extracellular PPi, the main endogenous inhibitor of vascular calcification, were investigated in the rat aorta. Calcium and magnesium have antagonist effects on PPi hydrolysis in the aortic wall. Km and Ki values for PPi hydrolysis in rat aortic rings were 1.1 mmol/L magnesium and 32 μmol/L calcium, respectively, but ATP hydrolysis was not affected with calcium. Calcium deposition in the rat aortic wall dramatically increased when the magnesium concentration was increased (ratio of Mg:Ca = 1:1; 1.5 mmol/L calcium and 1.5 mmol/L magnesium) respect to low magnesium concentration (ratio Mg:Ca = 1:3, 1.5 mmol/L calcium and 0.75 mmol/L magnesium). Data from observational clinical studies showing that the serum magnesium concentration is inversely correlated with vascular calcification could be reinterpreted as a compensatory regulatory mechanism that reduces both PPi hydrolysis and vascular calcification. The impact of magnesium in vascular calcification in humans could be studied in association with calcium levels, for example, as the magnesium:calcium ratio.

Intraprocedural left ventricular free wall rupture diagnosed by left ventriculogram in a patient with infero-posterior myocardial infarction and severe aortic stenosis.

PubMed

Konishi, Takao; Funayama, Naohiro; Yamamoto, Tadashi; Nishihara, Hiroshi; Hotta, Daisuke; Kikuchi, Kenjiro; Yokoyama, Hideo; Ohori, Katsumi

2016-06-06

Left ventricular wall rupture remains a major lethal complication of acute myocardial infarction and hypertension is a well-known predisposing factor of cardiac rupture after myocardial infarction. An 87-year-old man was admitted to our hospital, diagnosed as acute myocardial infarction (AMI). The echocardiogram showed 0.67-cm(2) aortic valve, consistent with severe aortic stenosis (AS). A coronary angiography showed a chronic occlusion of the proximal left circumflex artery and a 99 % stenosis and thrombus in the mid right coronary artery. During percutaneous angioplasty of the latter, transient hypotension and bradycardia developed at the time of balloon inflation, and low doses of noradrenaline and etilefrine were intravenously administered as needed. The patient suddenly lost consciousness and developed electro-mechanical dissociation. Cardio-pulmonary resuscitation followed by insertion of an intra-aortic balloon pump (IABP) and percutaneous cardiopulmonary support were initiated. The echocardiogram revealed moderate pericardial effusion, though the site of free wall rupture was not distinctly visible. A left ventriculogram clearly showed an infero-posterior apical wall rupture. Surgical treatment was withheld because of the interim development of brain death. In this patient, who presented with severe AS, the administration of catecholamine to stabilize the blood pressure probably increased the intraventricular pressures considerably despite apparently normal measurements of the central aortic pressure. IABP, temporary pacemaker, or both are recommended instead of intravenous catecholamines for patients with AMI complicated with significant AS to stabilize hemodynamic function during angioplasty.

Optical pathology study of human abdominal aorta tissues using confocal micro resonance Raman spectroscopy

NASA Astrophysics Data System (ADS)

Liu, Cheng-hui; Boydston-White, Susie; Wang, Wubao; Sordillo, Laura A.; Shi, Lingyan; Weisberg, Arel; Tomaselli, Vincent P.; Sordillo, Peter P.; Alfano, Robert R.

2016-03-01

Resonance Raman (RR) spectroscopic technique has a high potential for label-free and in-situ detection of biomedical lesions in vivo. This study evaluates the ability of RR spectroscopy method as an optical histopathology tool to detect the atherosclerotic plaque states of abdominal aorta in vitro. This part demonstrates the RR spectral molecular fingerprint features from different sites of the atherosclerotic abdominal aortic wall tissues. Total 57 sites of five pieces aortic samples in intimal and adventitial wall from an autopsy specimen were examined using confocal micro Raman system of WITec 300R with excitation wavelength of 532nm. The preliminary RR spectral biomarkers of molecular fingerprints indicated that typical calcified atherosclerotic plaque (RR peak at 964cm-1) tissue; fibrolipid plaque (RR peaks at 1007, 1161, 1517 and 2888cm-1) tissue, lipid pool with the fatty precipitation cholesterol) with collagen type I (RR peaks at 864, 1452, 1658, 2888 and 2948cm-1) in the soft tissue were observed and investigated.

Overexpression of Catalase in Vascular Smooth Muscle Cells Prevents the Formation of Abdominal Aortic Aneurysms

PubMed Central

Parastatidis, Ioannis; Weiss, Daiana; Joseph, Giji; Taylor, W Robert

2013-01-01

Objective Elevated levels of oxidative stress have been reported in abdominal aortic aneurysms (AAA), but which reactive oxygen species (ROS) promotes the development of AAA remains unclear. Here we investigate the effect of the hydrogen peroxide (H2O2) degrading enzyme catalase on the formation of AAA. Approach and Results AAA were induced with the application of calcium chloride (CaCl2) on mouse infrarenal aortas. The administration of PEG-catalase, but not saline, attenuated the loss of tunica media and protected against AAA formation (0.91±0.1 mm vs. 0.76±0.09 mm). Similarly, in a transgenic mouse model, catalase over-expression in the vascular smooth muscle cells (VSMC) preserved the thickness of tunica media and inhibited aortic dilatation by 50% (0.85±0.14 mm vs. 0.57±0.08 mm). Further studies showed that injury with CaCl2 decreased catalase expression and activity in the aortic wall. Pharmacologic administration or genetic over-expression of catalase restored catalase activity and subsequently decreased matrix metalloproteinase activity. In addition, a profound reduction in inflammatory markers and VSMC apoptosis was evident in aortas of catalase over-expressing mice. Interestingly, as opposed to infusion of PEG-catalase, chronic over-expression of catalase in VSMC did not alter the total aortic H2O2 levels. Conclusions The data suggest that a reduction in aortic wall catalase activity can predispose to AAA formation. Restoration of catalase activity in the vascular wall enhances aortic VSMC survival and prevents AAA formation primarily through modulation of matrix metalloproteinase activity. PMID:23950141

Intrauterine growth restriction is associated with persistent aortic wall thickening and glomerular proteinuria during infancy

PubMed Central

Zanardo, Vincenzo; Fanelli, Tiziana; Weiner, Gary; Fanos, Vassilios; Zaninotto, Martina; Visentin, Silvia; Cavallin, Francesco; Trevisanuto, Daniele; Cosmi, Erich

2011-01-01

Low birth weight, caused either by preterm birth or by intrauterine growth restriction, has recently been associated with increased rates of adult renal and cardiovascular disease. Since aortic intima–media thickening is a noninvasive marker of preclinical vascular disease, we compared abdominal aortic intima–media thickness among intrauterine growth restricted and equivalent gestational age fetuses in utero and at 18 months of age. The relationship between intrauterine growth restriction, fetal aortic thickening, and glomerular function during infancy was measured by enrolling 44 mothers with single-fetus pregnancies at 32 weeks gestation: 23 growth restricted and 21 of appropriate gestational age as controls. Abdominal aortic intima–media thickness was measured by ultrasound at enrollment and again at 18 months of age. Fetuses with intrauterine growth restriction had significantly higher abdominal aortic intima–media thickness compared with age controls when measured both in utero and at 18 months. At 18 months, the median urinary microalbumin and median albumin–creatinine ratio were significantly higher in those infants who experienced intrauterine growth restriction compared to the controls. Our results show that intrauterine growth restriction is associated with persistent aortic wall thickening and significantly higher microalbuminuria during infancy. PMID:21490588

Effect of cannula shape on aortic wall and flow turbulence: hydrodynamic study during extracorporeal circulation in mock thoracic aorta.

PubMed

Minakawa, Masahito; Fukuda, Ikuo; Yamazaki, Junichi; Fukui, Kozo; Yanaoka, Hideki; Inamura, Takao

2007-12-01

This study was designed to analyze flow pattern, velocity, and strain on the aortic wall of a glass aortic model during extracorporeal circulation, and to elucidate the characteristics of flow pattern in four aortic cannulas. Different patterns of large vortices and helical flow were made by each cannula. The high-velocity flow (0.6 m/s) was observed in end-hole cannula, causing high strain rate tensor (0.3~0.4 without unit) on the aortic arch. In dispersion cannula, a decreased strain rate tensor (less than 0.1) was found on the outer curvature of the aortic arch. In Soft-flow cannula (3M Cardiovascular, Ann Arbor, MI, USA), further decreased flow velocity (0.2 m/s) and strain (less than 0.2) were observed. In Select 3D cannula (Medtronic, Inc., Minneapolis, MN, USA), a high strain (0.4~0.5) was observed along the inner curvature of the aortic arch. In conclusion, end-hole cannula should not be used in atherosclerotic aorta. Particular attention should be paid both for selection of cannulas and cannulation site based on this result.

Stanford-A acute aortic dissection, inflammation, and metalloproteinases: a review.

PubMed

Cifani, Noemi; Proietta, Maria; Tritapepe, Luigi; Di Gioia, Cira; Ferri, Livia; Taurino, Maurizio; Del Porto, Flavia

2015-01-01

Acute aortic dissection (AAD) is a life-threatening disease with an incidence of about 2.6-3.6 cases per 100,000/year. Depending on the site of rupture, AAD is classified as Stanford-A when the ascending aortic thoracic tract and/or the arch are involved, and Stanford-B when the descending thoracic aorta and/or aortic abdominal tract are targeted. It was recently shown that inflammatory pathways underlie aortic rupture in both type A and type B Stanford AAD. An immune infiltrate has been found within the middle and outer tunics of dissected aortic specimens. It has also been observed that the recall and activation of macrophages inside the middle tunic are key events in the early phases of AAD. Macrophages are able to release metalloproteinases (MMPs) and pro-inflammatory cytokines which, in turn, give rise to matrix degradation and neoangiogenesis. An imbalance between the production of MMPs and MMP tissue inhibitors is pivotal in the extracellular matrix degradation underlying aortic wall remodelling in dissections occurring both in inherited conditions and in atherosclerosis. Among MMPs, MMP-12 is considered a specific marker of aortic wall disease, whatever the genetic predisposition may be. The aim of this review is, therefore, to take a close look at the immune-inflammatory mechanisms underlying Stanford-A AAD.

Abdominal Aortic Aneurysm (AAA)

MedlinePlus

... plaque buildup causes the walls of the abdominal aorta to become weak and bulge outward like a ... treated? What is an abdominal aortic aneurysm? The aorta, the largest artery in the body, is a ...

Computational Fluid Dynamics Analysis of Thoracic Aortic Dissection

NASA Astrophysics Data System (ADS)

Tang, Yik; Fan, Yi; Cheng, Stephen; Chow, Kwok

2011-11-01

Thoracic Aortic Dissection (TAD) is a cardiovascular disease with high mortality. An aortic dissection is formed when blood infiltrates the layers of the vascular wall, and a new artificial channel, the false lumen, is created. The expansion of the blood vessel due to the weakened wall enhances the risk of rupture. Computational fluid dynamics analysis is performed to study the hemodynamics of this pathological condition. Both idealized geometry and realistic patient configurations from computed tomography (CT) images are investigated. Physiological boundary conditions from in vivo measurements are employed. Flow configuration and biomechanical forces are studied. Quantitative analysis allows clinicians to assess the risk of rupture in making decision regarding surgical intervention.

Temporary closure of the abdominal wall by use of silicone rubber sheets after operative repair of ruptured abdominal aortic aneurysms.

PubMed

Akers, D L; Fowl, R J; Kempczinski, R F; Davis, K; Hurst, J M; Uhl, S

1991-07-01

Management of patients after operative repair of abdominal aortic aneurysms can be further complicated if primary closure of the abdominal wall cannot be technically accomplished or is associated with profound increases in intraabdominal and peak inspiratory pressures. We recently treated five patients with ruptured abdominal aortic aneurysms and one patient with a ruptured thoracoabdominal aneurysm whose abdominal incisions had to be closed with a Dacron reinforced, silicone sheet. All patients were hemodynamically unstable either at admission to the hospital or became so during operation. Four patients required the insertion of a silicone rubber sheet at the primary operation because of massive retroperitoneal hematoma or edema of the bowel wall or both. Incisions in two patients were closed primarily, but the patients required reexploration and secondary closure with silicone rubber sheets because of the development of marked increases in peak inspiratory pressures, intraabdominal pressures, and decreased urinary output. Four of the six patients subsequently underwent successful removal of the silicone rubber sheets with delayed primary closure of the abdominal wall, and two others died before removal. The patient with the ruptured thoracoabdominal aneurysm died on postoperative day 20 because of pulmonary sepsis but had a healed abdominal incision. The three surviving patients have been discharged. A silicone rubber sheet may be necessary for closure of the abdominal wall after repair of ruptured abdominal aortic aneurysm in patients where primary abdominal wall closure is impossible or where it results in compromise in respiratory or renal function.

Fracture mechanics of shear crack propagation and dissection in the healthy bovine descending aortic media.

PubMed

Haslach, Henry W; Siddiqui, Ahmed; Weerasooriya, Amanda; Nguyen, Ryan; Roshgadol, Jacob; Monforte, Noel; McMahon, Eileen

2018-03-01

This experimental study adopts a fracture mechanics strategy to investigate the mechanical cause of aortic dissection. Inflation of excised healthy bovine aortic rings with a cut longitudinal notch that extends into the media from the intima suggests that an intimal tear may propagate a nearly circumferential-longitudinal rupture surface that is similar to the delamination that occurs in aortic dissection. Radial and 45°-from-radial cut notch orientations, as seen in the thickness surface, produce similar circumferential crack propagation morphologies. Partial cut notches, whose longitudinal length is half the width of the ring, measure the influence of longitudinal material on crack propagation. Such specimens also produce circumferential cracks from the notch root that are visible in the thickness circumferential-radial plane, and often propagate a secondary crack from the base of the notch, visible in the intimal circumferential-longitudinal plane. Inflation of rings with pairs of cut notches demonstrates that a second notch modifies the propagation created in a specimen with a single notch. The circumferential crack propagation is likely a consequence of the laminar medial structure. These fracture surfaces are probably due to non-uniform circumferential shear deformation in the heterogeneous media as the aortic wall expands. The qualitative deformation morphology around the root of the cut notch during inflation is evidence for such shear deformation. The shear apparently results from relative slip in the circumferential direction of collagen fibers. The slip may produce shear in the longitudinal-circumferential plane between medial layers or in the radial-circumferential plane within a medial lamina in an idealized model. Circumferential crack propagation in the media is then a shear mechanical process that might be facilitated by disease of the tissue. An intimal tear of an apparently healthy aortic wall near the aortic arch is life-threatening because it may lead to full rupture or to wall dissection in which delamination of the medial layer extends around most of the aortic circumference. The mechanical events underlying dissection are not definitively established. This experimental fracture mechanics study provides evidence that shear rupture is the main mechanical process underlying aortic dissection. The commonly performed tensile strength tests of aortic tissue are not clinically useful to predict or describe aortic dissection. One implication of the study is that shear tests might produce more fruitful simple assessments of the aortic wall strength. A clinical implication is that when presented with an intimal tear, those who guide care might recommend steps to reduce the shear load on the aorta. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Suspension string: a new method of aortic valvuloplasty for aortic insufficiency and ventricular septal defect.

PubMed

Huang, Zhixiong

2006-09-01

In a 4-year-old boy with ventricular septal defect, severe aortic insufficiency, and mild infundibular stenosis, a new method was used to reconstruct the prolapsed aortic cusp. Two ends of a pledged stitch were passed through the aorta at each side of the right, noncoronary commissure and then through another pledget, and were then tied repeatedly in a row. The length of the row of knots was equal to that of the free edge of left coronary or noncoronary leaflet. The remainder of the stitch was passed through a pledget and then the aortic wall at each side of the left and right coronary commissure to the extraaortic wall pledget and were tied. A suspension string was formed by the row of knots and supported by a Teflon (Dupont Teflon, Wilmington, DE) felt pledget sandwich at each of two commissures. The free margin of the prolapsed cusp was attached to the suspension string by a continuous suture. The concomitant anomalies were corrected. The result was satisfactory.

In vitro flow assessment: from PC-MRI to computational fluid dynamics including fluid-structure interaction

NASA Astrophysics Data System (ADS)

Kratzke, Jonas; Rengier, Fabian; Weis, Christian; Beller, Carsten J.; Heuveline, Vincent

2016-04-01

Initiation and development of cardiovascular diseases can be highly correlated to specific biomechanical parameters. To examine and assess biomechanical parameters, numerical simulation of cardiovascular dynamics has the potential to complement and enhance medical measurement and imaging techniques. As such, computational fluid dynamics (CFD) have shown to be suitable to evaluate blood velocity and pressure in scenarios, where vessel wall deformation plays a minor role. However, there is a need for further validation studies and the inclusion of vessel wall elasticity for morphologies being subject to large displacement. In this work, we consider a fluid-structure interaction (FSI) model including the full elasticity equation to take the deformability of aortic wall soft tissue into account. We present a numerical framework, in which either a CFD study can be performed for less deformable aortic segments or an FSI simulation for regions of large displacement such as the aortic root and arch. Both of the methods are validated by means of an aortic phantom experiment. The computational results are in good agreement with 2D phase-contrast magnetic resonance imaging (PC-MRI) velocity measurements as well as catheter-based pressure measurements. The FSI simulation shows a characteristic vessel compliance effect on the flow field induced by the elasticity of the vessel wall, which the CFD model is not capable of. The in vitro validated FSI simulation framework can enable the computation of complementary biomechanical parameters such as the stress distribution within the vessel wall.

Epithelioid Angiosarcoma With Metastatic Disease After Endovascular Therapy of Abdominal Aortic Aneurysm

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

Schmehl, Joerg, E-mail: joerg.schmehl@med.uni-tuebingen.de; Scharpf, Marcus; Brechtel, Klaus

2012-02-15

Malignancies of the aortic wall represent a rare condition, and only a few reports have covered cases of sarcomas arising at the site of a prosthesis made of Dacron. A coincidence with endovascular repair has only been reported in one case to date. We report a patient with epithelioid angiosarcoma and metastatic disease, which was found in an aneurysmal sac after endovascular aortic repair for abdominal aortic aneurysm.

Aquaporin-1 facilitates pressure-driven water flow across the aortic endothelium.

PubMed

Nguyen, Tieuvi; Toussaint, Jimmy; Xue, Yan; Raval, Chirag; Cancel, Limary; Russell, Stewart; Shou, Yixin; Sedes, Omer; Sun, Yu; Yakobov, Roman; Tarbell, John M; Jan, Kung-ming; Rumschitzki, David S

2015-05-01

Aquaporin-1, a ubiquitous water channel membrane protein, is a major contributor to cell membrane osmotic water permeability. Arteries are the physiological system where hydrostatic dominates osmotic pressure differences. In the present study, we show that the walls of large conduit arteries constitute the first example where hydrostatic pressure drives aquaporin-1-mediated transcellular/transendothelial flow. We studied cultured aortic endothelial cell monolayers and excised whole aortas of male Sprague-Dawley rats with intact and inhibited aquaporin-1 activity and with normal and knocked down aquaporin-1 expression. We subjected these systems to transmural hydrostatic pressure differences at zero osmotic pressure differences. Impaired aquaporin-1 endothelia consistently showed reduced engineering flow metrics (transendothelial water flux and hydraulic conductivity). In vitro experiments with tracers that only cross the endothelium paracellularly showed that changes in junctional transport cannot explain these reductions. Percent reductions in whole aortic wall hydraulic conductivity with either chemical blocking or knockdown of aquaporin-1 differed at low and high transmural pressures. This observation highlights how aquaporin-1 expression likely directly influences aortic wall mechanics by changing the critical transmural pressure at which its sparse subendothelial intima compresses. Such compression increases transwall flow resistance. Our endothelial and historic erythrocyte membrane aquaporin density estimates were consistent. In conclusion, aquaporin-1 significantly contributes to hydrostatic pressure-driven water transport across aortic endothelial monolayers, both in culture and in whole rat aortas. This transport, and parallel junctional flow, can dilute solutes that entered the wall paracellularly or through endothelial monolayer disruptions. Lower atherogenic precursor solute concentrations may slow their intimal entrainment kinetics. Copyright © 2015 the American Physiological Society.

Aquaporin-1 facilitates pressure-driven water flow across the aortic endothelium

PubMed Central

Nguyen, Tieuvi; Toussaint, Jimmy; Xue, Yan; Raval, Chirag; Cancel, Limary; Russell, Stewart; Shou, Yixin; Sedes, Omer; Sun, Yu; Yakobov, Roman; Tarbell, John M.; Jan, Kung-ming

2015-01-01

Aquaporin-1, a ubiquitous water channel membrane protein, is a major contributor to cell membrane osmotic water permeability. Arteries are the physiological system where hydrostatic dominates osmotic pressure differences. In the present study, we show that the walls of large conduit arteries constitute the first example where hydrostatic pressure drives aquaporin-1-mediated transcellular/transendothelial flow. We studied cultured aortic endothelial cell monolayers and excised whole aortas of male Sprague-Dawley rats with intact and inhibited aquaporin-1 activity and with normal and knocked down aquaporin-1 expression. We subjected these systems to transmural hydrostatic pressure differences at zero osmotic pressure differences. Impaired aquaporin-1 endothelia consistently showed reduced engineering flow metrics (transendothelial water flux and hydraulic conductivity). In vitro experiments with tracers that only cross the endothelium paracellularly showed that changes in junctional transport cannot explain these reductions. Percent reductions in whole aortic wall hydraulic conductivity with either chemical blocking or knockdown of aquaporin-1 differed at low and high transmural pressures. This observation highlights how aquaporin-1 expression likely directly influences aortic wall mechanics by changing the critical transmural pressure at which its sparse subendothelial intima compresses. Such compression increases transwall flow resistance. Our endothelial and historic erythrocyte membrane aquaporin density estimates were consistent. In conclusion, aquaporin-1 significantly contributes to hydrostatic pressure-driven water transport across aortic endothelial monolayers, both in culture and in whole rat aortas. This transport, and parallel junctional flow, can dilute solutes that entered the wall paracellularly or through endothelial monolayer disruptions. Lower atherogenic precursor solute concentrations may slow their intimal entrainment kinetics. PMID:25659484

Bicuspid aortic valves are associated with increased wall and turbulence shear stress levels compared to trileaflet aortic valves.

PubMed

Saikrishnan, Neelakantan; Mirabella, Lucia; Yoganathan, Ajit P

2015-06-01

Congenital bicuspid aortic valves (BAVs) are associated with accelerated disease progression, such as leaflet calcification and ascending aorta dilatation. Although common underlying genetic factors have been implicated in accelerated disease in BAV patients, several studies have suggested that altered hemodynamics also play a role in this disease process. The present study compares turbulence and wall shear stress (WSS) measurements between various BAV and trileaflet aortic valve (TAV) models to provide information for mechanobiological models of BAV disease. BAV and TAV models were constructed from excised porcine aortic valves to simulate parametric variations in BAV stenosis, hemodynamics and geometry. Particle image velocimetry experiments were conducted at physiological pressure conditions to characterize velocity fields in the ascending aorta. The velocity fields were post-processed to calculate turbulence, viscous and wall shear stresses in the ascending aorta. Stenosed BAV models showed the presence of eccentric systolic jets, causing increased WSS. Lower cardiac output resulted in a narrower jet, lower turbulence and lower viscous shear stress (VSS). The specific severe stenosis BAV model studied here showed reduced WSS due to reduction in non-fused leaflet mobility. Dilation of the aorta did not affect any turbulence or VSS, but reduced the WSS. In comparison with BAVs, TAVs have similar VSS values, but much smaller WSS and turbulence levels. These increased turbulence  and WSS levels in BAVs may play a key role in amplifying the biological responses of the ascending aorta wall and valvular leaflets, and support the hemodynamic underpinnings of BAV disease processes.

Impact of magnesium:calcium ratio on calcification of the aortic wall

PubMed Central

2017-01-01

Objective An inverse relationship between serum magnesium concentration and vascular calcification has been reported following observational clinical studies. Moreover, several studies have been suggesting a protective effect of magnesium on the vascular calcification. However, the exact mechanism remains elusive, and investigators have speculated among a myriad of potential actions. The effect of magnesium on calcification of the aortic wall is yet to be investigated. In the present study, the effects of magnesium and calcium on the metabolism of extracellular PPi, the main endogenous inhibitor of vascular calcification, were investigated in the rat aorta. Approach and results Calcium and magnesium have antagonist effects on PPi hydrolysis in the aortic wall. Km and Ki values for PPi hydrolysis in rat aortic rings were 1.1 mmol/L magnesium and 32 μmol/L calcium, respectively, but ATP hydrolysis was not affected with calcium. Calcium deposition in the rat aortic wall dramatically increased when the magnesium concentration was increased (ratio of Mg:Ca = 1:1; 1.5 mmol/L calcium and 1.5 mmol/L magnesium) respect to low magnesium concentration (ratio Mg:Ca = 1:3, 1.5 mmol/L calcium and 0.75 mmol/L magnesium). Conclusion Data from observational clinical studies showing that the serum magnesium concentration is inversely correlated with vascular calcification could be reinterpreted as a compensatory regulatory mechanism that reduces both PPi hydrolysis and vascular calcification. The impact of magnesium in vascular calcification in humans could be studied in association with calcium levels, for example, as the magnesium:calcium ratio. PMID:28570619

C-reactive protein in degenerative aortic valve stenosis

PubMed Central

Sanchez, Pedro L; Mazzone, AnnaMaria

2006-01-01

Degenerative aortic valve stenosis includes a range of disorder severity from mild leaflet thickening without valve obstruction, "aortic sclerosis", to severe calcified aortic stenosis. It is a slowly progressive active process of valve modification similar to atherosclerosis for cardiovascular risk factors, lipoprotein deposition, chronic inflammation, and calcification. Systemic signs of inflammation, as wall and serum C-reactive protein, similar to those found in atherosclerosis, are present in patients with degenerative aortic valve stenosis and may be expression of a common disease, useful in monitoring of stenosis progression. PMID:16774687

Evaluation of Aortic Blood Flow and Wall Shear Stress in Aortic Stenosis and Its Association With Left Ventricular Remodeling

PubMed Central

von Knobelsdorff-Brenkenhoff, Florian; Karunaharamoorthy, Achudhan; Trauzeddel, Ralf Felix; Barker, Alex J; Blaszczyk, Edyta; Markl, Michael; Schulz-Menger, Jeanette

2016-01-01

Background Aortic stenosis (AS) leads to variable stress for the left ventricle (LV) and consequently a broad range of LV remodeling. Study aim was to describe blood flow patterns in the ascending aorta of AS patients and determine their association with remodeling. Methods and Results Thirty-seven patients with AS (14 mild, 8 moderate, 15 severe; age 63±13 years) and 37 healthy controls (age 60±10 years) underwent 4D-flow MRI. Helical and vortical flow formations and flow eccentricity were assessed in the ascending aorta. Normalized flow displacement from the vessel center and peak systolic wall shear stress (WSSpeak) in the ascending aorta were quantified. LV remodeling was assessed based on LV mass index (LVMI-I) and the ratio of LV mass to enddiastolic volume (relative wall mass; RWM). Marked helical and vortical flow formation and eccentricity were more prevalent in patients with AS than in healthy subjects, and AS patients exhibited an asymmetric and elevated distribution of WSSpeak. In AS, aortic orifice area was strongly negatively associated with vortical flow formation (p=0.0274), eccentricity (p=0.0070) and flow displacement (p=0.0021). Bicuspid aortic valve was associated with more intense helical (p=0.0098) and vortical flow formation (p=0.0536), higher flow displacement (p=0.11) and higher WSSpeak (p=0.0926). LVM-I and RWM were significantly associated with aortic orifice area (p=0.0611, p=0.0058) and flow displacement (p=0.0058, p=0.0283). Conclusions In this pilot study, AS leads to abnormal blood flow pattern and WSSpeak in the ascending aorta. In addition to aortic orifice area, normalized flow displacement was significantly associated with LV remodeling. PMID:26917824

Functional Heart Valve Scaffolds Obtained by Complete Decellularization of Porcine Aortic Roots in a Novel Differential Pressure Gradient Perfusion System

PubMed Central

Sierad, Leslie Neil; Shaw, Eliza Laine; Bina, Alexander; Brazile, Bryn; Rierson, Nicholas; Patnaik, Sourav S.; Kennamer, Allison; Odum, Rebekah; Cotoi, Ovidiu; Terezia, Preda; Branzaniuc, Klara; Smallwood, Harrison; Deac, Radu; Egyed, Imre; Pavai, Zoltan; Szanto, Annamaria; Harceaga, Lucian; Suciu, Horatiu; Raicea, Victor; Olah, Peter; Simionescu, Agneta; Liao, Jun; Movileanu, Ionela

2015-01-01

There is a great need for living valve replacements for patients of all ages. Such constructs could be built by tissue engineering, with perspective of the unique structure and biology of the aortic root. The aortic valve root is composed of several different tissues, and careful structural and functional consideration has to be given to each segment and component. Previous work has shown that immersion techniques are inadequate for whole-root decellularization, with the aortic wall segment being particularly resistant to decellularization. The aim of this study was to develop a differential pressure gradient perfusion system capable of being rigorous enough to decellularize the aortic root wall while gentle enough to preserve the integrity of the cusps. Fresh porcine aortic roots have been subjected to various regimens of perfusion decellularization using detergents and enzymes and results compared to immersion decellularized roots. Success criteria for evaluation of each root segment (cusp, muscle, sinus, wall) for decellularization completeness, tissue integrity, and valve functionality were defined using complementary methods of cell analysis (histology with nuclear and matrix stains and DNA analysis), biomechanics (biaxial and bending tests), and physiologic heart valve bioreactor testing (with advanced image analysis of open–close cycles and geometric orifice area measurement). Fully acellular porcine roots treated with the optimized method exhibited preserved macroscopic structures and microscopic matrix components, which translated into conserved anisotropic mechanical properties, including bending and excellent valve functionality when tested in aortic flow and pressure conditions. This study highlighted the importance of (1) adapting decellularization methods to specific target tissues, (2) combining several methods of cell analysis compared to relying solely on histology, (3) developing relevant valve-specific mechanical tests, and (4) in vitro testing of valve functionality. PMID:26467108

Improvement of aortic valve stenosis by ApoA-I mimetic therapy is associated with decreased aortic root and valve remodelling in mice

PubMed Central

Trapeaux, J; Busseuil, D; Shi, Y; Nobari, S; Shustik, D; Mecteau, M; El-Hamamsy, I; Lebel, M; Mongrain, R; Rhéaume, E; Tardif, J-C

2013-01-01

Background and Purpose We have shown that infusions of apolipoprotein A-I (ApoA-I) mimetic peptide induced regression of aortic valve stenosis (AVS) in rabbits. This study aimed at determining the effects of ApoA-I mimetic therapy in mice with calcific or fibrotic AVS. Experimental Approach Apolipoprotein E-deficient (ApoE−/−) mice and mice with Werner progeria gene deletion (WrnΔhel/Δhel) received high-fat diets for 20 weeks. After developing AVS, mice were randomized to receive saline (placebo group) or ApoA-I mimetic peptide infusions (ApoA-I treated groups, 100 mg·kg−1 for ApoE−/− mice; 50 mg·kg−1 for Wrn mice), three times per week for 4 weeks. We evaluated effects on AVS using serial echocardiograms and valve histology. Key Results Aortic valve area (AVA) increased in both ApoE−/− and Wrn mice treated with the ApoA-I mimetic compared with placebo. Maximal sinus wall thickness was lower in ApoA-I treated ApoE−/− mice. The type I/III collagen ratio was lower in the sinus wall of ApoA-I treated ApoE−/− mice compared with placebo. Total collagen content was reduced in aortic valves of ApoA-I treated Wrn mice. Our 3D computer model and numerical simulations confirmed that the reduction in aortic root wall thickness resulted in improved AVA. Conclusions and Implications ApoA-I mimetic treatment reduced AVS by decreasing remodelling and fibrosis of the aortic root and valve in mice. PMID:23638718

Aortic outflow occlusion predicts rupture of abdominal aortic aneurysm.

PubMed

Crawford, Jeffrey D; Chivukula, Venkat Keshav; Haller, Stephen; Vatankhah, Nasibeh; Bohannan, Colin J; Moneta, Gregory L; Rugonyi, Sandra; Azarbal, Amir F

2016-12-01

Current threshold recommendations for elective abdominal aortic aneurysm (AAA) repair are based solely on maximal AAA diameter. Peak wall stress (PWS) has been demonstrated to be a better predictor than AAA diameter of AAA rupture risk. However, PWS calculations are time-intensive, not widely available, and therefore not yet clinically practical. In addition, PWS analysis does not account for variations in wall strength between patients. We therefore sought to identify surrogate clinical markers of increased PWS and decreased aortic wall strength to better predict AAA rupture risk. Patients treated at our institution from 2001 to 2014 for ruptured AAA (rAAA) were retrospectively identified and grouped into patients with small rAAA (maximum diameter <6 cm) or large rAAA (>6 cm). Patients with large (>6 cm) non-rAAA were also identified sequentially from 2009 for comparison. Demographics, vascular risk factors, maximal aortic diameter, and aortic outflow occlusion (AOO) were recorded. AOO was defined as complete occlusion of the common, internal, or external iliac artery. Computational fluid dynamics and finite element analysis simulations were performed to calculate wall stress distributions and to extract PWS. We identified 61 patients with rAAA, of which 15 ruptured with AAA diameter <60 mm (small rAAA group). Patients with small rAAAs were more likely to have peripheral arterial disease (PAD) and chronic obstructive pulmonary disease (COPD) than were patients in the large non-rAAA group. Patients with small rAAAs were also more likely to have AOO compared with non-rAAAs >60 mm (27% vs 8%; P = .047). Among all patients with rAAAs, those with AOO ruptured at smaller mean AAA diameters than in patients without AOO (62.1 ± 11.8 mm vs 72.5 ± 16.4 mm; P = .024). PWS calculations of a representative small rAAA and a large non-rAAA showed a substantial increase in PWS with AOO. We demonstrate that AOO, PAD, and COPD in AAA are associated with rAAAs at smaller diameters. AOO appears to increase PWS, whereas COPD and PAD may be surrogate markers of decreased aortic wall strength. We therefore recommend consideration of early, elective AAA repair in patients with AOO, PAD, or COPD to minimize risk of early rupture. Copyright © 2016. Published by Elsevier Inc.

Effects of increased left ventricular wall thickness on the myocardium in severe aortic stenosis with normal left ventricular ejection fraction: Two- and three-dimensional multilayer speckle tracking echocardiography.

PubMed

Cho, Eun Jeong; Park, Sung-Ji; Kim, Eun Kyoung; Lee, Ga Yeon; Chang, Sung-A; Choi, Jin-Oh; Lee, Sang-Chol; Park, Seung Woo

2017-04-01

The aim of this study was to determine the capability of real time three-dimensional echocardiography (RT3DE) and two-dimensional (2D) multilayer speckle tracking echocardiography (MSTE) for evaluation of early myocardial dysfunction triggered by increased left ventricular (LV) wall thickness in severe aortic stenosis (AS) with normal LV ejection fraction (EF≥55%). Conventional, RT3D STE and 2D MSTE were performed in 45 patients (mean 68.9±9.0 years) with severe AS (aortic valve area <1 cm 2 , aortic velocity Vmax >4 m/s or mean PG >40 mm Hg) and normal left ventricular ejection fraction (LVEF) without overt coronary artery disease and in 18 age-, sex-matched healthy controls. Global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were calculated using RT3DE and MSTE. The severe AS group had lower 3D GLS, GRS, GAS and 2D epicardium, and mid-wall and endocardium GLS compared to healthy controls. In MSTE analysis, 2D LS and CS values decreased from the endocardial layer toward the epicardial layer. Severe AS patients with increased LV wall thickness had lower 3D GLS and 2D epicardium, and mid-wall and endocardium GLS compared with severe AS patients without LV wall thickening. GLS on RT3D STE was correlated with GLS on 2D MSTE, left ventricular mass index, LVEF, left atrial volume index, and lnNT-proBNP. RT3DE and 2D MSTE can be used to identify subtle contractile dysfunction triggered by increased LV wall thickness in severe AS with normal LVEF. Therefore, RT3D STE and 2D MSTE may provide additional information that can facilitate decision-making regarding severe AS patients with increased LV wall thickness and normal LV function. © 2017, Wiley Periodicals, Inc.

Diuretics prevent Rho-kinase activation and expression of profibrotic/oxidative genes in the hypertensive aortic wall.

PubMed

Araos, Patricio; Mondaca, David; Jalil, Jorge E; Yañez, Cristián; Novoa, Ulises; Mora, Italo; Ocaranza, María Paz

2016-12-01

Diuretics are current antihypertensive drugs since they reduce blood pressure and cardiovascular risk. Increased vascular tone is modulated in a relevant way by the RhoA/Rho-kinase (ROCK) pathway, by acting on vascular smooth muscle cell contraction. This pathway has also proremodeling vascular effects. There are few data on the role of diuretics on both vascular ROCK activation and on proremodeling effects. We assessed the effects of hydrochlorothiazide (HCTZ) and spironolactone (spiro) alone and in combination with the ROCK inhibitor fasudil (FAS) on ROCK activation, gene expression of proremodeling markers and on hypertrophy in the aortic wall of hypertensive rats. Deoxycorticosterone acetate (DOCA)-salt hypertensive rats (male, Sprague-Dawley) were randomized to the specific ROCK inhibitor FAS, HCTZ, spiro or the combinations of FAS/HCTZ or FAS/spiro for 3 weeks. At the end of the study, ROCK activation (by western blot), gene expression of proremodeling markers (by reverse transcription polymerase chain reaction, RT-PCR) and vascular hypertrophy (by morphometry) were determined in the aortic wall. All treatments significantly reduced blood pressure. In the DOCA rats the p-myosin phosphatase target protein-1 (MYPT1)/t-MYPT1 ratio, index of ROCK activation was higher by 2.8 fold (p < 0.05) compared with control rats. All treatments reduced ROCK activation in the aortic wall to control levels (p < 0.05). Besides, significantly increased protein levels of transforming growth factor β1 (TGF-β 1 ), gene expression of TGF-β 1 , connective tissue growth factor (CTGF), p22 phox and gp91 phox subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, as well as increased media thickness and aortic media area/lumen area (AM/LA) in the untreated hypertensive rats were significantly reduced (p < 0.05) to control levels by all treatments. Similar effects were observed using both diuretics alone or in combination with FAS. In the aortic wall, both HCTZ and spiro in antihypertensive doses reduce ROCK activation, subsequent expression of genes that promote vascular remodeling and hypertrophy in this experimental model of hypertension. These effects could explain some of their clinical benefits in hypertensive patients. © The Author(s), 2016.

Diuretics prevent Rho-kinase activation and expression of profibrotic/oxidative genes in the hypertensive aortic wall

PubMed Central

Araos, Patricio; Mondaca, David; Jalil, Jorge E.; Yañez, Cristián; Novoa, Ulises; Mora, Italo; Ocaranza, María Paz

2016-01-01

Background: Diuretics are current antihypertensive drugs since they reduce blood pressure and cardiovascular risk. Increased vascular tone is modulated in a relevant way by the RhoA/Rho-kinase (ROCK) pathway, by acting on vascular smooth muscle cell contraction. This pathway has also proremodeling vascular effects. There are few data on the role of diuretics on both vascular ROCK activation and on proremodeling effects. We assessed the effects of hydrochlorothiazide (HCTZ) and spironolactone (spiro) alone and in combination with the ROCK inhibitor fasudil (FAS) on ROCK activation, gene expression of proremodeling markers and on hypertrophy in the aortic wall of hypertensive rats. Methods: Deoxycorticosterone acetate (DOCA)-salt hypertensive rats (male, Sprague–Dawley) were randomized to the specific ROCK inhibitor FAS, HCTZ, spiro or the combinations of FAS/HCTZ or FAS/spiro for 3 weeks. At the end of the study, ROCK activation (by western blot), gene expression of proremodeling markers (by reverse transcription polymerase chain reaction, RT-PCR) and vascular hypertrophy (by morphometry) were determined in the aortic wall. Results: All treatments significantly reduced blood pressure. In the DOCA rats the p-myosin phosphatase target protein-1 (MYPT1)/t-MYPT1 ratio, index of ROCK activation was higher by 2.8 fold (p < 0.05) compared with control rats. All treatments reduced ROCK activation in the aortic wall to control levels (p < 0.05). Besides, significantly increased protein levels of transforming growth factor β1 (TGF-β1), gene expression of TGF-β1, connective tissue growth factor (CTGF), p22 phox and gp91 phox subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, as well as increased media thickness and aortic media area/lumen area (AM/LA) in the untreated hypertensive rats were significantly reduced (p < 0.05) to control levels by all treatments. Similar effects were observed using both diuretics alone or in combination with FAS. Conclusions: In the aortic wall, both HCTZ and spiro in antihypertensive doses reduce ROCK activation, subsequent expression of genes that promote vascular remodeling and hypertrophy in this experimental model of hypertension. These effects could explain some of their clinical benefits in hypertensive patients. PMID:27587602

Percutaneous coronary angioplasty of a left anterior descending artery implanted on a Dacron coronary prosthesis on an aortic conduit.

PubMed

Drobinski, G; Thomas, D; Funck, F; Metzger, J P; Canny, M; Grosgogeat, Y

1986-08-01

Certain surgical techniques may make it difficult to catheterize the coronary ostia and perform percutaneous coronary angioplasty. We report the case of a 48 year old patient who developed unstable angina four years after a Bentall's procedure with reimplantation of the coronary arteries on a Dacron coronary prosthesis. The anginal pain was related to very severe stenosis of the proximal segment of the left anterior descending artery. The difficulties encountered during the dilatation procedure were due to: (a) the ectopic position of the ostium of the prosthesis on the anterior aortic wall; (b) the forces exerted on the aortic prosthesis wall and on the valvular prosthesis during positioning of the guiding catheter which were poorly tolerated and induced a vagal reaction; (c) the direction taken by the distal tip of the guiding catheter, perpendicular to the wall of the aortic prosthesis; (d) the sinuosity of the arterial trajectory: the left coronary segment of the coronary prosthesis was directed towards the left circumflex artery rather than towards the left anterior descending artery. Coronary angioplasty succeeded after relatively complex technical procedures: special guiding catheter, unusual intra-aortic manoeuvres for positioning the guiding catheter, dilatation catheter change on a 3-metre long guide wire in order to cross the stenotic segment; this was performed with a super low-profiled dilatation catheter. There were no complications and anginal pain disappeared.

18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.

PubMed

Courtois, Audrey; Nusgens, Betty V; Hustinx, Roland; Namur, Gauthier; Gomez, Pierre; Somja, Joan; Defraigne, Jean-Olivier; Delvenne, Philippe; Michel, Jean-Baptiste; Colige, Alain C; Sakalihasan, Natzi

2013-10-01

Rupture of abdominal aortic aneurysms (AAAs) leads to a significant morbidity and mortality in aging populations, and its prediction would be most beneficial to public health. Spots positive for uptake of (18)F-FDG detected by PET are found in 12% of AAA patients (PET+), who are most often symptomatic and at high rupture risk. Comparing the (18)F-FDG-positive site with a negative site from the same aneurysm and with samples collected from AAA patients with no (18)F-FDG uptake should allow the discrimination of biologic alterations that would help in identifying markers predictive of rupture. Biopsies of the AAA wall were obtained from patients with no (18)F-FDG uptake (PET0, n = 10) and from PET+ patients (n = 8), both at the site positive for uptake and at a distant negative site of the aneurysmal wall. Samples were analyzed by immunohistochemistry, quantitative real-time polymerase chain reaction, and zymography. The sites of the aneurysmal wall with a positive (18)F-FDG uptake were characterized by a strikingly increased number of adventitial inflammatory cells, highly proliferative, and by a drastic reduction of smooth muscle cells (SMCs) in the media as compared with their negative counterpart and with the PET0 wall. The expression of a series of genes involved in the maintenance and remodeling of the wall was significantly modified in the negative sites of PET+, compared with the PET0 wall, suggesting a systemic alteration of the aneurysmal wall. Furthermore, a striking increase of several matrix metalloproteinases (MMPs), notably the MMP1 and MMP13 collagenases, was observed in the positive sites, mainly in the adventitia. Moreover, PET+ patients were characterized by a higher circulating C-reactive protein. Positive (18)F-FDG uptake in the aneurysmal wall is associated with an active inflammatory process characterized by a dense infiltrate of proliferating leukocytes in the adventitia and an increased circulating C-reactive protein. Moreover, a loss of SMC in the media and alterations of the expression of genes involved in the remodeling of adventitia and collagen degradation potentially participate in the weakening of the aneurysmal wall preceding rupture.

Left ventricular remodeling and hypertrophy in patients with aortic stenosis: insights from cardiovascular magnetic resonance

PubMed Central

2012-01-01

Background Cardiovascular magnetic resonance (CMR) is the gold standard non-invasive method for determining left ventricular (LV) mass and volume but has not been used previously to characterise the LV remodeling response in aortic stenosis. We sought to investigate the degree and patterns of hypertrophy in aortic stenosis using CMR. Methods Patients with moderate or severe aortic stenosis, normal coronary arteries and no other significant valve lesions or cardiomyopathy were scanned by CMR with valve severity assessed by planimetry and velocity mapping. The extent and patterns of hypertrophy were investigated using measurements of the LV mass index, indexed LV volumes and the LV mass/volume ratio. Asymmetric forms of remodeling and hypertrophy were defined by a regional wall thickening ≥13 mm and >1.5-fold the thickness of the opposing myocardial segment. Results Ninety-one patients (61±21 years; 57 male) with aortic stenosis (aortic valve area 0.93±0.32cm2) were recruited. The severity of aortic stenosis was unrelated to the degree (r2=0.012, P=0.43) and pattern (P=0.22) of hypertrophy. By univariate analysis, only male sex demonstrated an association with LV mass index (P=0.02). Six patterns of LV adaption were observed: normal ventricular geometry (n=11), concentric remodeling (n=11), asymmetric remodeling (n=11), concentric hypertrophy (n=34), asymmetric hypertrophy (n=14) and LV decompensation (n=10). Asymmetric patterns displayed considerable overlap in appearances (wall thickness 17±2mm) with hypertrophic cardiomyopathy. Conclusions We have demonstrated that in patients with moderate and severe aortic stenosis, the pattern of LV adaption and degree of hypertrophy do not closely correlate with the severity of valve narrowing and that asymmetric patterns of wall thickening are common. Trial registration ClinicalTrials.gov Reference Number: NCT00930735 PMID:22839417

Comparison of idiopathic (isolated) aortitis and giant cell arteritis-related aortitis. A French retrospective multicenter study of 117 patients.

PubMed

Espitia, Olivier; Samson, Maxime; Le Gallou, Thomas; Connault, Jérôme; Landron, Cedric; Lavigne, Christian; Belizna, Cristina; Magnant, Julie; de Moreuil, Claire; Roblot, Pascal; Maillot, François; Diot, Elisabeth; Jégo, Patrick; Durant, Cécile; Masseau, A; Brisseau, Jean-Marie; Pottier, Pierre; Espitia-Thibault, Alexandra; Santos, Anabele Dos; Perrin, François; Artifoni, Mathieu; Néel, Antoine; Graveleau, Julie; Moreau, Philippe; Maisonneuve, Hervé; Fau, Georges; Serfaty, Jean-Michel; Hamidou, Mohamed; Agard, Christian

2016-06-01

The aim of the study was to compare clinical/imaging findings and outcome in patients with idiopathic (isolated aortitis, IA) and with giant cell arteritis (GCA)-related aortitis. Patients from 11 French internal medicine departments were retrospectively included. Aortitis was defined by aortic wall thickening >2mm and/or an aortic aneurysm on CT-scan, associated to inflammatory syndrome. Patients with GCA had at least 3 ACR criteria. Aortic events (aneurysm, dissection, aortic surgeries) were reported, and free of aortic events-survival were compared. Among 191 patients with non-infectious aortitis, 73 with GCA and 44 with IA were included. Patients with IA were younger (65 vs 70 years, p=0.003) and comprised more past/current smokers (43 vs 15%, p=0.0007). Aortic aneurisms were more frequent (38% vs 20%, p=0.03), and aortic wall thickening was more pronounced in IA. During follow-up (median=34 months), subsequent development of aortic aneurysm was significantly lower in GCA when compared to IA (p=0.009). GCA patients required significantly less aortic surgery during follow-up than IA patients (p=0.02). Mean age, sex ratio, inflammatory parameters, and free of aortic aneurism survival were equivalent in patients with IA ≥ 60 years when compared to patients with GCA-related aortitis. IA is more severe than aortitis related to GCA, with higher proportions of aortic aneurism at diagnosis and during follow-up. IA is a heterogeneous disease and its prognosis is worse in younger patients <60 years. Most patients with IA ≥ 60 years share many features with GCA-related aortitis. Copyright © 2016 Elsevier B.V. All rights reserved.

Microcirculatory perfusion shift in the gut wall layers induced by extracorporeal circulation.

PubMed

Kalder, Johannes; Ajah, Dieudonne; Keschenau, Paula; Kennes, Lieven N; Tolba, Rene; Kokozidou, Maria; Jacobs, Michael J; Koeppel, Thomas A

2015-02-01

Extracorporeal circulation (ECC) is regularly applied to maintain organ perfusion during major aortic and cardiovascular surgery. During thoracoabdominal aortic repair, ECC-driven selective visceral arterial perfusion (SVP) results in changed microcirculatory perfusion (shift from the muscularis toward the mucosal small intestinal layer) in conjunction with macrohemodynamic hypoperfusion. The underlying mechanism, however, is unclear. Therefore, the aim of this study was to assess in a porcine model whether ECC itself or the hypoperfusion induced by SVP is responsible for the mucosal/muscular shift in the small intestinal wall. A thoracoabdominal aortic approach was performed in 15 healthy pigs divided equally into three groups: group I, control; group II, thoracic aortic cross-clamping with distal aortic perfusion; and group III, thoracic aortic cross-clamping with distal aortic perfusion and SVP. Macrocirculatory and microcirculatory blood flow was assessed by transit time ultrasound volume flow measurement and fluorescent microspheres. In addition, markers for metabolism and intestinal ischemia-reperfusion injury were determined. ECC with a roller pump induced a significant switch from the muscularis and mucosal layer of the small intestine, even with adequate macrocirculation (mucosal/muscular perfusion ratio: group I vs II, P = .005; group I vs III, P = .0018). Furthermore, the oxygen extraction ratio increased significantly in groups II (>30%) and III (>40%) in the beginning of the ECC compared with the control (group I vs II, P = .0037; group I vs III, P = .0062). Lactate concentrations and pH values did not differ between groups I and II; but group III demonstrated a significant shifting toward a lactate-associated acidosis (lactate: group I vs III, P = .0031; pH: group I vs III, P = .0001). We demonstrated a significant shifting between the small intestinal gut wall layers induced by roller pump-driven ECC. The shift occurs independently of macrohemodynamics, with a significant effect on aerobic metabolism in the gut wall. Consequently, an optimal intestinal perfusion cannot be guaranteed by a roller pump; therefore, perfusion techniques need to be optimized. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

The conundrum of arterial stiffness, elevated blood pressure, and aging.

PubMed

AlGhatrif, Majd; Lakatta, Edward G

2015-02-01

Isolated systolic hypertension is a major health burden that is expanding with the aging of our population. There is evidence that central arterial stiffness contributes to the rise in systolic blood pressure (SBP); at the same time, central arterial stiffening is accelerated in patients with increased SBP. This bidirectional relationship created a controversy in the field on whether arterial stiffness leads to hypertension or vice versa. Given the profound interdependency of arterial stiffness and blood pressure, this question seems intrinsically challenging, or probably naïve. The aorta's function of dampening the pulsatile flow generated by the left ventricle is optimal within a physiological range of distending pressure that secures the required distal flow, keeps the aorta in an optimal mechanical conformation, and minimizes cardiac work. This homeostasis is disturbed by age-associated, minute alterations in aortic hemodynamic and mechanical properties that induce short- and long-term alterations in each other. Hence, it is impossible to detect an "initial insult" at an epidemiological level. Earlier manifestations of these alterations are observed in young adulthood with a sharp decline in aortic strain and distensibility accompanied by an increase in diastolic blood pressure. Subsequently, aortic mechanical reserve is exhausted, and aortic remodeling with wall stiffening and dilatation ensue. These two phenomena affect pulse pressure in opposite directions and different magnitudes. With early remodeling, there is an increase in pulse pressure, due to the dominance of arterial wall stiffness, which in turn accelerates aortic wall stiffness and dilation. With advanced remodeling, which appears to be greater in men, the effect of diameter becomes more pronounced and partially offsets the effect of wall stiffness leading to plateauing in pulse pressure in men and slower increase in pulse pressure (PP) than that of wall stiffness in women. The complex nature of the hemodynamic changes with aging makes the "one-size-fits-all" approach suboptimal and urges for therapies that address the vascular profile that underlies a given blood pressure, rather than the blood pressure values themselves.

Relationship of Aortic Wall Distensibility to Mitral and Aortic Valve Calcification: The Multi-Ethnic Study of Atherosclerosis.

PubMed

Cohoon, Kevin P; Criqui, Michael H; Budoff, Matthew J; Lima, Joao A; Blaha, Michael J; Decker, Paul A; Durazo, Ramon; Liu, Kiang; Kramer, Holly

2018-05-01

Data are limited on whether valvular calcification is associated with aortic wall stiffness. We tested whether aortic valve calcification (AVC) and/or mitral valve calcification (MVC) is inversely associated with aortic distensibility (AD). Cross-sectional study conducted in a subset of the Multi-Ethnic Study of Atherosclerosis (MESA) included 3676 MESA participants aged 44 to 84 years with AD measured with magnetic resonance imaging and with AVC and MVC measured with noncontrast cardiac computed tomography scans. Both AVC and MVC were divided into 3 categories: zero, < median values (low), and ≥ median values (high) for patients with nonzero values. Overall, 88% (n = 3256) and 92% (n = 3365) of participants had zero AVC and MVC, while 6% (n = 211) and 4% (n = 156) had low, and 6% (n = 209) and 4% (n = 155) had high values of AVC and MVC, respectively. The AVC was independently associated with AD after adjusting for age, gender, and ethnicity ( P = .035). No association was noted between AVC groups and AD after adjustment for all covariates or MVC groups and AD in any model.

Pathophysiological Factors Associated with Left Ventricular Perforation in Transcatheter Aortic Valve Implantation by Transfemoral Approach.

PubMed

Owais, Tamer; El Garhy, Mohammad; Fuchs, Jürgen; Disha, Kushtrim; Elkaffas, Sameh; Breuer, Martin; Lauer, Bernward; Kuntze, Thomas

2017-07-01

Left ventricular (LV) perforation is one of the rare and most serious complications of transcatheter aortic valve implantation (TAVI). The study aim was to determine the pathophysiological factors associated with this serious complication. A retrospective study was conducted of pathophysiological factors shown in echocardiograms and computed tomography angiograms performed preoperatively in patients who developed LV perforation during transfemoral TAVI (study group) with regards to anatomic and functional variables. Results were then compared with data acquired from a randomly selected sample of patients without perforation (control group). Among 963 TAVI cases, LV perforation occurred in 11 patients (three males, eight females; mean age 79 years). These patients showed complications of LV perforation that required emergency sternotomy and repair of injury to the left ventricle. Ten patients were rescued by the procedure, but one patient died during surgery. Focus on preoperative factors and intraoperative steps was established in favor to identify possible predictors of LV perforation. A LV cavity size <4.2 cm and a hypercontractile ventricle were identified in 10 patients (90%). Only one patient had a dilated cardiomyopathic left ventricle, with a cavity size of 6.1 cm and an ejection fraction of 10%. The present study results revealed other specific patient-related factors, namely a narrow aorto-mitral angle and a thin ventricular muscular wall despite long-standing aortic stenosis. All 11 patients had an average mid-LV muscular wall thickness of 5 mm. An inverse proportional relationship between the aorto-mitral angle and the incidence of perforation was noted, where in all 11 patients the wire had directed itself towards the anterior free wall of the left ventricle, where it induced injury. A small LV cavity, a hypercontractile state, a thin muscular wall, and a narrow aorto-mitral angle may be considered potential predictors of the occurrence of LV perforation during TAVI.

Suppressive effects of dietary EPA-rich fish oil on the degradation of elastin fibers in the aortic wall in nicotine-administered mice.

PubMed

Kugo, Hirona; Zaima, Nobuhiro; Onozato, Megumi; Miyamoto, Chie; Hashimoto, Keisuke; Yanagimoto, Kenichi; Moriyama, Tatsuya

2017-08-01

Abdominal aortic aneurysm (AAA) is a vascular disease involving gradual dilation of the abdominal aorta. Recent studies suggest that nicotine, which is a primary component in cigarette smoke, is closely associated with the development and rupture of an AAA. Nicotine accelerates AAA development through the weakening of the vascular wall by increasing oxidative stress and matrix metalloproteinase (MMP)-2 expression. However, little is known about preventing the AAA induced by nicotine. A non-surgical means of preventing the weakening of the vascular wall before the onset of AAA by functional food factors would be a valuable option over surgery. Fish oil is a functional food that is rich in n-3 polyunsaturated fatty acids that have an anti-inflammatory effect. In this study, we evaluated the effect of dietary fish oil on the weakening of the aortic wall due to nicotine administration in a mouse model. Histological analysis showed that the dietary fish oil suppressed the degradation of elastin fibers in the nicotine-administered mice. Additionally, the dietary fish oil suppressed the protein level of MMP-12, macrophage infiltration, and the oxidative stress in the vascular wall. These results suggest that fish oil could suppress the weakening of the vascular wall by suppressing the elastin fiber degradation caused by nicotine. By suppressing the nicotine induced weakening of the vascular wall, fish oil might help prevent the development of AAA.

Expression of platelet-derived growth factor B is upregulated in patients with thoracic aortic dissection.

PubMed

Meng, Weixin; Liu, Shangdian; Li, Dandan; Liu, Zonghong; Yang, Hui; Sun, Bo; Liu, Hongyu

2018-04-20

Thoracic aortic dissection (TAD) is a serious condition requiring urgent treatment to avoid catastrophic consequences. The inflammatory response is involved in the occurrence and development of TAD, possibly potentiated by platelet-derived growth factors (PDGFs). This study aimed to determine whether expression of PDGF-B (a subunit of PDGF-BB) was increased in TAD patients and to explore the factors responsible for its upregulation and subsequent effects on TAD. Full-thickness ascending aorta wall specimens from TAD patients (n = 15) and control patients (n = 10) were examined for expression of PDGF-B and its receptor (PDGFRB) and in terms of morphology, inflammation, and fibrosis. Blood samples from TAD and control patients were collected to detect plasma levels of PDGF-BB and soluble elastins. Expression levels of PDGF-B, PDGFRB, and collagen I were significantly enhanced in ascending aorta wall specimens from TAD patients compared with controls. Furthermore, soluble elastic fragments and PDGF-BB were significantly increased in plasma from TAD patients compared with controls, and numerous irregular elastic fibers and macrophages were seen in the ascending aorta wall in TAD patients. An increase in elastic fragments in the aorta wall might be responsible for inducing the activation and migration of macrophages to injured sites, leading to elevated expression of PDGF-B, which in turn induces deposition of collagen, disrupts extracellular matrix homeostasis, and increases the stiffness of the aorta wall, resulting in compromised aorta compliance. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Relation of murine thoracic aortic structural and cellular changes with aging to passive and active mechanical properties.

PubMed

Wheeler, Jason B; Mukherjee, Rupak; Stroud, Robert E; Jones, Jeffrey A; Ikonomidis, John S

2015-02-25

Maintenance of the structure and mechanical properties of the thoracic aorta contributes to aortic function and is dependent on the composition of the extracellular matrix and the cellular content within the aortic wall. Age-related alterations in the aorta include changes in cellular content and composition of the extracellular matrix; however, the precise roles of these age-related changes in altering aortic mechanical function are not well understood. Thoracic aortic rings from the descending segment were harvested from C57BL/6 mice aged 6 and 21 months. Thoracic aortic diameter and wall thickness were higher in the old mice. Cellular density was reduced in the medial layer of aortas from the old mice; concomitantly, collagen content was higher in old mice, but elastin content was similar between young and old mice. Stress relaxation, an index of compliance, was reduced in aortas from old mice and correlated with collagen fraction. Contractility of the aortic rings following potassium stimulation was reduced in old versus young mice. Furthermore, collagen gel contraction by aortic smooth muscle cells was reduced with age. These results demonstrate that numerous age-related structural changes occurred in the thoracic aorta and were related to alterations in mechanical properties. Aortic contractility decreased with age, likely because of a reduction in medial cell number in addition to a smooth muscle contractile deficit. Together, these unique findings provide evidence that the age-related changes in structure and mechanical function coalesce to provide an aortic substrate that may be predisposed to aortopathies. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Scan-rescan reproducibility of segmental aortic wall shear stress as assessed by phase-specific segmentation with 4D flow MRI in healthy volunteers.

PubMed

van der Palen, Roel L F; Roest, Arno A W; van den Boogaard, Pieter J; de Roos, Albert; Blom, Nico A; Westenberg, Jos J M

2018-05-26

The aim was to investigate scan-rescan reproducibility and observer variability of segmental aortic 3D systolic wall shear stress (WSS) by phase-specific segmentation with 4D flow MRI in healthy volunteers. Ten healthy volunteers (age 26.5 ± 2.6 years) underwent aortic 4D flow MRI twice. Maximum 3D systolic WSS (WSSmax) and mean 3D systolic WSS (WSSmean) for five thoracic aortic segments over five systolic cardiac phases by phase-specific segmentations were calculated. Scan-rescan analysis and observer reproducibility analysis were performed. Scan-rescan data showed overall good reproducibility for WSSmean (coefficient of variation, COV 10-15%) with moderate-to-strong intraclass correlation coefficient (ICC 0.63-0.89). The variability in WSSmax was high (COV 16-31%) with moderate-to-good ICC (0.55-0.79) for different aortic segments. Intra- and interobserver reproducibility was good-to-excellent for regional aortic WSSmax (ICC ≥ 0.78; COV ≤ 17%) and strong-to-excellent for WSSmean (ICC ≥ 0.86; COV ≤ 11%). In general, ascending aortic segments showed more WSSmax/WSSmean variability compared to aortic arch or descending aortic segments for scan-rescan, intraobserver and interobserver comparison. Scan-rescan reproducibility was good for WSSmean and moderate for WSSmax for all thoracic aortic segments over multiple systolic phases in healthy volunteers. Intra/interobserver reproducibility for segmental WSS assessment was good-to-excellent. Variability of WSSmax is higher and should be taken into account in case of individual follow-up or in comparative rest-stress studies to avoid misinterpretation.

Enhanced delineation of degradation in aortic walls through OCT

NASA Astrophysics Data System (ADS)

Real, Eusebio; Val-Bernal, José Fernando; Revuelta, José M.; Pontón, Alejandro; Calvo Díez, Marta; Mayorga, Marta; López-Higuera, José M.; Conde, Olga M.

2015-03-01

Degradation of the wall of human ascending thoracic aorta has been assessed through Optical Coherence Tomography (OCT). OCT images of the media layer of the aortic wall exhibit micro-structure degradation in case of diseased aortas from aneurysmal vessels or in aortas prone to aortic dissections. The degeneration in vessel walls appears as low-reflectivity areas due to the invasive appearance of acidic polysaccharides and mucopolysaccharides within a typical ordered microstructure of parallel lamellae of smooth muscle cells, elastin and collagen fibers. An OCT indicator of wall degradation can be generated upon the spatial quantification of the extension of degraded areas in a similar way as conventional histopathology. This proposed OCT marker offers a real-time clinical insight of the vessel status to help cardiovascular surgeons in vessel repair interventions. However, the delineation of degraded areas on the B-scan image from OCT is sometimes difficult due to presence of speckle noise, variable SNR conditions on the measurement process, etc. Degraded areas could be outlined by basic thresholding techniques taking advantage of disorders evidences in B-scan images, but this delineation is not always optimum and requires complex additional processing stages. This work proposes an optimized delineation of degraded spots in vessel walls, robust to noisy environments, based on the analysis of the second order variation of image intensity of backreflection to determine the type of local structure. Results improve the delineation of wall anomalies providing a deeper physiological perception of the vessel wall conditions. Achievements could be also transferred to other clinical scenarios: carotid arteries, aorto-iliac or ilio-femoral sections, intracranial, etc.

Strain measurement of abdominal aortic aneurysm with real-time 3D ultrasound speckle tracking.

PubMed

Bihari, P; Shelke, A; Nwe, T H; Mularczyk, M; Nelson, K; Schmandra, T; Knez, P; Schmitz-Rixen, T

2013-04-01

Abdominal aortic aneurysm rupture is caused by mechanical vascular tissue failure. Although mechanical properties within the aneurysm vary, currently available ultrasound methods assess only one cross-sectional segment of the aorta. This study aims to establish real-time 3-dimensional (3D) speckle tracking ultrasound to explore local displacement and strain parameters of the whole abdominal aortic aneurysm. Validation was performed on a silicone aneurysm model, perfused in a pulsatile artificial circulatory system. Wall motion of the silicone model was measured simultaneously with a commercial real-time 3D speckle tracking ultrasound system and either with laser-scan micrometry or with video photogrammetry. After validation, 3D ultrasound data were collected from abdominal aortic aneurysms of five patients and displacement and strain parameters were analysed. Displacement parameters measured in vitro by 3D ultrasound and laser scan micrometer or video analysis were significantly correlated at pulse pressures between 40 and 80 mmHg. Strong local differences in displacement and strain were identified within the aortic aneurysms of patients. Local wall strain of the whole abdominal aortic aneurysm can be analysed in vivo with real-time 3D ultrasound speckle tracking imaging, offering the prospect of individual non-invasive rupture risk analysis of abdominal aortic aneurysms. Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

External aortic wrap for repair of type 1 endoleak☆

PubMed Central

Dean, Anastasia; Yap, Swee Leong; Bhamidipaty, Venu; Pond, Franklin

2014-01-01

INTRODUCTION Type 1 endoleak is a rare complication after endovascular abdominal aortic aneurysm repair (EVAR) with a reported frequency up to 2.88%. It is a major risk factor for aneurysmal enlargement and rupture. PRESENTATION OF CASE We present a case of a 68 year old gentleman who was found to have a proximal type 1 endoleak with loss of graft wall apposition on routine surveillance imaging post-EVAR. An initial attempt at endovascular repair was unsuccessful. Given the patient's multiple medical co-morbidities, which precluded the possibility of conventional graft explantation and open repair, we performed a novel surgical technique which did not require aortic cross-clamping. A double-layered Dacron wrap was secured around the infra-renal aorta with Prolene sutures, effectively hoisting the posterior bulge to allow wall to graft apposition and excluding the endoleak. Post-operative CT angiogram showed resolution of the endoleak and a stable sac size. DISCUSSION Several anatomical factors need to be considered when this technique is proposed including aortic neck angulation, position of lumbar arteries and peri-aortic venous anatomy. While an external wrap technique has been investigated sporadically for vascular aneurysms, to our knowledge there is only one similar case in the literature. CONCLUSION Provided certain anatomical features are present, an external aortic wrap is a useful and successful option to manage type 1 endoleak in high-risk patients who are unsuitable for aortic clamping. PMID:25217878

Endovascular Treatment of Thoracic Aortic Dissection: Hemodynamic Shear Stress Study

NASA Astrophysics Data System (ADS)

Tang, Yik Sau; Lai, Siu Kai; Cheng, Stephen Wing Keung; Chow, Kwok Wing

2012-11-01

Thoracic Aortic Dissection (TAD), a life threatening cardiovascular disease, occurs when blood intrudes into the layers of the aortic wall, creating a new artificial channel (the false lumen) beside the original true lumen. The weakened false lumen wall may expand, enhancing the risk of rupture and resulting in high mortality. Endovascular treatment involves the deployment of a stent graft into the aorta, thus blocking blood from entering the false lumen. Due to the irregular geometry of the aorta, the stent graft, however, may fail to conform to the vessel curvature, and would create a ``bird-beak'' configuration, a wedge-shaped domain between the graft and the vessel wall. Computational fluid dynamics analysis is employed to study the hemodynamics of this pathological condition. With the `beaking' configuration, the local hemodynamic shear stress will drop below the threshold of safety reported earlier in the literature. The oscillating behavior of the shear stress might lead to local inflammation, atherosclerosis and other undesirable consequences. Supported by the Innovation and Technology Fund of the Hong Kong Government.

Identification of vessel wall anomalies in thoracic aortic aneurysms through optical coherence tomography and gradient-based strategies

NASA Astrophysics Data System (ADS)

Eguizabal, Alma; Real, Eusebio; Pontón, Alejandro; Calvo Diez, Marta; Val-Bernal, J. Fernando; Mayorga, Marta; Revuelta, José M.; López-Higuera, José M.; Conde, Olga M.

2014-05-01

Optical Coherence Tomography is a natural candidate for imaging biological structures just under tissue surface. Human thoracic aorta from aneurysms reveal elastin disorders and smooth muscle cell alterations when visualizing the media layer of the aortic wall, which is only some tens of microns in depth from surface. The resulting images require a suitable processing to enhance interesting disorder features and to use them as indicators for wall degradation, converting OCT into a hallmark for diagnosis of risk of aneurysm under intraoperative conditions. This work proposes gradient-based digital image processing approaches to conclude this risk. These techniques are believed to be useful in these applications as aortic wall disorders directly affect the refractive index of the tissue, having an effect on the gradient of the tissue reflectivity that conform the OCT image. Preliminary results show that the direction of the gradient contains information to estimate the tissue abnormality score. The detection of the edges of the OCT image is performed using the Canny algorithm. The edges delineate tissue disorders in the region of interest and isolate the abnormalities. These edges can be quantified to estimate a degradation score. Furthermore, the direction of the gradient seems to be a promising enhancement technique, as it detects areas of homogeneity in the region of interest. Automatic results from gradient-based strategies are finally compared to the histopathological global aortic score, which accounts for each risk factor presence and seriousness.

A Migrated Aortic Stent Graft Causing Erosive Spondylopathy

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

Gestrich, Christopher, E-mail: christopher.gestrich@ukb.uni-bonn.de; Probst, Chris, E-mail: chris.probst@ukb.uni-bonn.de; Wilhelm, Kai, E-mail: kai.wilhelm@ek-bonn.de

We report about a patient presenting with back pain 4 months after an uneventful endovascular implantation of an aortic stent graft. Computed tomography scan revealed a migration of the stent with consecutive endoleakage, kink formation, and movement of the stent toward the spine, which caused destruction of the aortic wall as well as vertebral necrosis. Explantation of the stent and replacement of the native aorta relieved the patient of his symptoms.

Hemodynamic Study of Flow Remodeling Stent Graft for the Treatment of Highly Angulated Abdominal Aortic Aneurysm

PubMed Central

Yeow, Siang Lin; Leo, Hwa Liang

2016-01-01

This study investigates the effect of a novel flow remodeling stent graft (FRSG) on the hemodynamic characteristics in highly angulated abdominal aortic aneurysm based on computational fluid dynamics (CFD) approach. An idealized aortic aneurysm with varying aortic neck angulations was constructed and CFD simulations were performed on nonstented models and stented models with FRSG. The influence of FRSG intervention on the hemodynamic performance is analyzed and compared in terms of flow patterns, wall shear stress (WSS), and pressure distribution in the aneurysm. The findings showed that aortic neck angulations significantly influence the velocity flow field in nonstented models, with larger angulations shifting the mainstream blood flow towards the center of the aorta. By introducing FRSG treatment into the aneurysm, erratic flow recirculation pattern in the aneurysm sac diminishes while the average velocity magnitude in the aneurysm sac was reduced in the range of 39% to 53%. FRSG intervention protects the aneurysm against the impacts of high velocity concentrated flow and decreases wall shear stress by more than 50%. The simulation results highlighted that FRSG may effectively treat aneurysm with high aortic neck angulations via the mechanism of promoting thrombus formation and subsequently led to the resorption of the aneurysm. PMID:27247612

Pulsatile extracorporeal circulation during on-pump cardiac surgery enhances aortic wall shear stress.

PubMed

Assmann, Alexander; Benim, Ali Cemal; Gül, Fethi; Lux, Philipp; Akhyari, Payam; Boeken, Udo; Joos, Franz; Feindt, Peter; Lichtenberg, Artur

2012-01-03

Controversy on superiority of pulsatile versus non-pulsatile extracorporeal circulation in cardiac surgery still continues. Stroke as one of the major adverse events during cardiopulmonary bypass is, in the majority of cases, caused by mobilization of aortic arteriosclerotic plaques that is inducible by pathologically elevated wall shear stress values. The present study employs computational fluid dynamics to evaluate the aortic blood flow and wall shear stress profiles under the influence of antegrade or retrograde perfusion with pulsatile versus non-pulsatile extracorporeal circulation. While, compared to physiological flow, a non-pulsatile perfusion resulted in generally decreased blood velocities and only moderately increased shear forces (48 Pa versus 20 Pa antegradely and 127 Pa versus 30 Pa retrogradely), a pulsatile perfusion extensively enhanced the occurrence of turbulences, maximum blood flow speed and maximum wall shear stress (1020 Pa versus 20 Pa antegradely and 1178 Pa versus 30 Pa retrogradely). Under these circumstances arteriosclerotic embolism has to be considered. Further simulations and experimental work are necessary to elucidate the impact of our findings on the scientific discourse of pulsatile versus non-pulsatile extracorporeal circulation. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Arterial involvements in hereditary dysplasia of the connective tissue].

PubMed

Beylot, C; Doutre, M S; Beylot-Barry, M; Busquet, M

1994-03-01

Arterial involvement is an important feature of the diagnosis and, above all, prognosis of heritable disorders of connective tissue. In pseudoxanthoma elasticum, a progressive occlusive syndrome is associated with hemorrhage and especially with gastrointestinal bleeding. Aneurysms are uncommon. Hypertension occurs frequently. Cutaneous signs (yellowish pseudo xanthomatous papules of the large folds) the ocular changes (angioid streaks) and pathology showing numerous, thickened, fragmented, disorganized, calcified elastic fibers in the deep dermis and arterial walls, allow the diagnosis to be made. In the heterogeneous group of Ehlers-Danlos syndromes, type IV is characterized by sudden spontaneous rupture of the large arteries. Aneurysms and carotido-cavernous fistulae are rather frequent. Owing to friability of the arterial walls, arteriograms and other procedure requiring arterial puncture may prove hazardous and surgery difficult. Such patients have an acrogeric morphotype, and thin, fragile skin, but cutaneous hyperelasticity and joint hyperlaxity are usually minimal. Pathology evidences collagen hypoplasia in the skin and arterial walls. The severity of Marfan syndrome is due to aortic involvement. A fusiform aneurysm of the ascending aorta represents a vital risk of rupture. Aortic root dilatation is associated and responsible of severe aortic regurgitation. Aortic dissection is also a serious threat. Improved surgical techniques for repairing a dilated or dissected aortic root with simultaneous replacement of the aortic valve increases the life expectancy of such patients. Dolichomorphism is the characteristic skeletal abnormality, particularly with arachnodactyly and upward ectopia lentis, which is almost bilateral, is a very frequent feature of Marfan syndrome. The most typical histological finding is aortic cystic median necrosis. The basic defect in Marfan syndrome concerns the fibrillin, whose gene is located on chromosome 15. The three diseases detailed in this paper constitute the main areas of this subject, but arterial involvement may occur in other inheritable disorders of connective tissue (osteogenesis imperfecta, cutis laxa, Werner syndrome, Menkes syndrome, etc).

Implementation of visual data mining for unsteady blood flow field in an aortic aneurysm.

PubMed

Morizawa, Seiichiro; Shimoyama, Koji; Obayashi, Shigeru; Funamoto, Kenichi; Hayase, Toshiyuki

2011-12-01

This study was performed to determine the relations between the features of wall shear stress and aneurysm rupture. For this purpose, visual data mining was performed in unsteady blood flow simulation data for an aortic aneurysm. The time-series data of wall shear stress given at each grid point were converted to spatial and temporal indices, and the grid points were sorted using a self-organizing map based on the similarity of these indices. Next, the results of cluster analysis were mapped onto the real space of the aortic aneurysm to specify the regions that may lead to aneurysm rupture. With reference to previous reports regarding aneurysm rupture, the visual data mining suggested specific hemodynamic features that cause aneurysm rupture. GRAPHICAL ABSTRACT:

Marfan syndrome, magnesium status and medical prevention of cardiovascular complications by hemodynamic treatments and antisense gene therapy.

PubMed

Igondjo-Tchen, S; Pagès, N; Bac, P; Godeau, G; Durlach, J

2003-03-01

The medical management of Marfan Syndrome (MFS) mainly relies on early prevention of the aortic complications. Hemodynamic treatments try to diminish the forcefulness of cardiac contractions and to reduce blood pressure: for example long term administration of propranolol may significantly reduce the rate of increase in aortic ratio (aortic diameter/expected aortic diameter). Retardation of aortic dilatation may be most often observed by early treatment started when the baseline end-diastolic aortic root diameter is < 40 mm. It seems better to use beta-blockers without intrinsic sympathomimetic activity. Successful acceptance of beta-blockers may be limited by side-effects, but the efficiency of alternative hypotensive agents (calcium channel inhibitors, ACE inhibitors) is not yet validated. Gene therapy might constitute an etiologic specific treatment of MFS. FBN1-RZ1 hammerhead antisense ribozyme is able to suppress expression of the mutant FBN1 allele. The use of ribozymes as systemic therapeutic agents will depend on efficient delivery to its target, but the various proposed vectors raise yet unsolved problems. A hydrogel angioplasty balloon might be a possible vector for delivering an antisense ribozyme in the aortic wall specifically. Ribozymes--as deoxyribonucleotides--may be taken up by tissue upon local application. Further research should study ex vivo local application of antisense ribozyme on human aortic wall, before assessing in vivo efficiency and tolerance of this aortic local vectorisation. It is always necessary to maintain a balanced magnesium intake in patients with MFS. Firstly to prevent the multiple noxious effects of magnesium deficiency on cardiovascular targets. Secondly to ensure the best efficiency and the least toxicity of the hemodynamic drugs used as long term prophylactic treatment for cardiovascular complications and of the etiologic antisense magnesium-dependent gene therapy, in the future.

Investigation of pulsatile flowfield in healthy thoracic aorta models.

PubMed

Wen, Chih-Yung; Yang, An-Shik; Tseng, Li-Yu; Chai, Jyh-Wen

2010-02-01

Cardiovascular disease is the primary cause of morbidity and mortality in the western world. Complex hemodynamics plays a critical role in the development of aortic dissection and atherosclerosis, as well as many other diseases. Since fundamental fluid mechanics are important for the understanding of the blood flow in the cardiovascular circulatory system of the human body aspects, a joint experimental and numerical study was conducted in this study to determine the distributions of wall shear stress and pressure and oscillatory WSS index, and to examine their correlation with the aortic disorders, especially dissection. Experimentally, the Phase-Contrast Magnetic Resonance Imaging (PC-MRI) method was used to acquire the true geometry of a normal human thoracic aorta, which was readily converted into a transparent thoracic aorta model by the rapid prototyping (RP) technique. The thoracic aorta model was then used in the in vitro experiments and computations. Simulations were performed using the computational fluid dynamic (CFD) code ACE+((R)) to determine flow characteristics of the three-dimensional, pulsatile, incompressible, and Newtonian fluid in the thoracic aorta model. The unsteady boundary conditions at the inlet and the outlet of the aortic flow were specified from the measured flowrate and pressure results during in vitro experiments. For the code validation, the predicted axial velocity reasonably agrees with the PC-MRI experimental data in the oblique sagittal plane of the thoracic aorta model. The thorough analyses of the thoracic aorta flow, WSSs, WSS index (OSI), and wall pressures are presented. The predicted locations of the maxima of WSS and the wall pressure can be then correlated with that of the thoracic aorta dissection, and thereby may lead to a useful biological significance. The numerical results also suggest that the effects of low WSS and high OSI tend to cause wall thickening occurred along the inferior wall of the aortic arch and the anterior wall of the brachiocephalic artery, similar implication reported in a number of previous studies.

In vitro investigation of a novel elastic vascular prosthesis for valve-sparing aortic root and ascending aorta replacement.

PubMed

Scharfschwerdt, Michael; Leonhard, Moritz; Lehmann, Judith; Richardt, Doreen; Goldmann, Helmut; Sievers, Hans-Hinrich

2016-05-01

Prosthetic replacement of the thoracic aorta with common Dacron prostheses impairs the aortic 'windkessel' and, in valve-sparing procedures, also aortic valve function. Elastic graft material may overcome these deficiencies. Fresh porcine aortas including the root were set up in a mock circulation before and after replacement of the ascending part with a novel vascular prosthesis providing elastic behaviours. In a first series (n = 14), haemodynamics and leaflet motions of the aortic valve were investigated and also cyclic changes of aortic dimensions at different levels of the root. In a second series (n = 7), intravascular pressure and dimensions of the proximal descending aorta were measured and the corresponding wall tension was calculated. Haemodynamics of the aortic valve remain comparable after replacement. Though the novel prosthesis does not feature such high distensibility as the native aorta, the dynamic of the root was significantly increased compared with common Dacron prostheses at the commissural level, preserving 'windkessel' function. Thus, wall tension of the residual aorta remained unchanged; nevertheless, maximum pressure-time differential dp/dt increased by 13%. The use of the novel elastic prosthesis for replacement of the ascending aorta seems to be beneficial, especially with regard to the preservation of the aortic windkessel. Further studies will be needed to clarify long-term utilization of the material in vivo. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Regional and directional compliance of the healthy aorta: an ex vivo study in a porcine model.

PubMed

Krüger, Tobias; Veseli, Kujtim; Lausberg, Henning; Vöhringer, Luise; Schneider, Wilke; Schlensak, Christian

2016-07-01

To gain differential knowledge about the physiological compliance and wall strength of the different regions of the aorta, including the ascending aorta, arch and descending aorta in both the circumferential and longitudinal directions, and to generate a hypothesis on the pathophysiological mechanisms that lead to Type A aortic dissection. Fresh tissue specimens from 22 ex vivo porcine aortas were analysed on a tensile tester. Regional and directional compliance, failure stress and failure strain were recorded. Aortic compliance appeared as a linear function of the natural logarithm (ln) of wall stress. Compliance significantly decreased along the length of the aorta. In the ascending aorta, longitudinal compliance significantly (P = 0.003) exceeded circumferential compliance, and the outer curvature was more compliant than the inner curvature (P = 0.03). In the descending aorta, this relationship is reversed: the circumferential compliance exceeded the longitudinal compliance, and the outer aspect was more compliant (P = 0.003). The median circumferential failure stress of all aortic segments was in the range of 2000-2750 kPa, whereas the longitudinal failure stress in the ascending aorta and the arch had values of 750-1000 kPa, which were significantly lower (P < 0.05). Surprisingly, the longitudinal failure stress of the inner aspect of the descending aorta was extraordinarily high (2000 kPa). Failure strain, similar to compliance, was highest in the ascending aorta and decreased along the aorta. The aorta appears to be a complex organ with distinct regional and directional differences in compliance and wall strength that is designed to effectively absorb the kinetic energy of cardiac systole and to cushion the momentum of systolic impact. Under normotensive conditions and a preconditioned physiological morphology, the aortic wall works in the steep part of the logarithmic strain-stress function; under hypertensive conditions and pathological morphology, the wall reacts in an non-compliant manner. The high longitudinal compliance and low failure stress of the ascending aorta and subsequent pathological changes may be the main determinants of the recurrent patho-anatomy of Type A aortic dissection. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Regional and directional compliance of the healthy aorta: an ex vivo study in a porcine model†

PubMed Central

Krüger, Tobias; Veseli, Kujtim; Lausberg, Henning; Vöhringer, Luise; Schneider, Wilke; Schlensak, Christian

2016-01-01

OBJECTIVES To gain differential knowledge about the physiological compliance and wall strength of the different regions of the aorta, including the ascending aorta, arch and descending aorta in both the circumferential and longitudinal directions, and to generate a hypothesis on the pathophysiological mechanisms that lead to Type A aortic dissection. METHODS Fresh tissue specimens from 22 ex vivo porcine aortas were analysed on a tensile tester. Regional and directional compliance, failure stress and failure strain were recorded. RESULTS Aortic compliance appeared as a linear function of the natural logarithm (ln) of wall stress. Compliance significantly decreased along the length of the aorta. In the ascending aorta, longitudinal compliance significantly (P = 0.003) exceeded circumferential compliance, and the outer curvature was more compliant than the inner curvature (P = 0.03). In the descending aorta, this relationship is reversed: the circumferential compliance exceeded the longitudinal compliance, and the outer aspect was more compliant (P = 0.003). The median circumferential failure stress of all aortic segments was in the range of 2000–2750 kPa, whereas the longitudinal failure stress in the ascending aorta and the arch had values of 750–1000 kPa, which were significantly lower (P < 0.05). Surprisingly, the longitudinal failure stress of the inner aspect of the descending aorta was extraordinarily high (2000 kPa). Failure strain, similar to compliance, was highest in the ascending aorta and decreased along the aorta. CONCLUSION The aorta appears to be a complex organ with distinct regional and directional differences in compliance and wall strength that is designed to effectively absorb the kinetic energy of cardiac systole and to cushion the momentum of systolic impact. Under normotensive conditions and a preconditioned physiological morphology, the aortic wall works in the steep part of the logarithmic strain–stress function; under hypertensive conditions and pathological morphology, the wall reacts in an non-compliant manner. The high longitudinal compliance and low failure stress of the ascending aorta and subsequent pathological changes may be the main determinants of the recurrent patho-anatomy of Type A aortic dissection. PMID:26993474

Microarray analysis to identify the similarities and differences of pathogenesis between aortic occlusive disease and abdominal aortic aneurysm.

PubMed

Wang, Guofu; Bi, Lechang; Wang, Gaofeng; Huang, Feilai; Lu, Mingjing; Zhu, Kai

2018-06-01

Objectives Expression profile of GSE57691 was analyzed to identify the similarities and differences between aortic occlusive disease and abdominal aortic aneurysm. Methods The expression profile of GSE57691 was downloaded from Gene Expression Omnibus database, including 20 small abdominal aortic aneurysm samples, 29 large abdominal aortic aneurysm samples, 9 aortic occlusive disease samples, and 10 control samples. Using the limma package in R, the differentially expressed genes were screened. Followed by enrichment analysis was performed for the differentially expressed genes using database for annotation, visualization, and integrated discovery online tool. Based on string online tool and Cytoscape software, protein-protein interaction network and module analyses were carried out. Moreover, integrated TF platform database and Cytoscape software were used for constructing transcriptional regulatory networks. Results As a result, 1757, 354, and 396 differentially expressed genes separately were identified in aortic occlusive disease, large abdominal aortic aneurysm, and small abdominal aortic aneurysm samples. UBB was significantly enriched in proteolysis related pathways with a high degree in three groups. SPARCL1 was another gene shared by these groups and regulated by NFIA, which had a high degree in transcriptional regulatory network. ACTB, a significant upregulated gene in abdominal aortic aneurysm samples, could be regulated by CLIC4, which was significantly enriched in cell motions. ACLY and NFIB were separately identified in aortic occlusive disease and small abdominal aortic aneurysm samples, and separately enriched in lipid metabolism and negative regulation of cell proliferation. Conclusions The downregulated UBB, NFIA, and SPARCL1 might play key roles in both aortic occlusive disease and abdominal aortic aneurysm, while the upregulated ACTB might only involve in abdominal aortic aneurysm. ACLY and NFIB were specifically involved in aortic occlusive disease and small abdominal aortic aneurysm separately.

Analysis of flow patterns in a patient-specific aortic dissection model.

PubMed

Cheng, Z; Tan, F P P; Riga, C V; Bicknell, C D; Hamady, M S; Gibbs, R G J; Wood, N B; Xu, X Y

2010-05-01

Aortic dissection is the most common acute catastrophic event affecting the thoracic aorta. The majority of patients presenting with an uncomplicated type B dissection are treated medically, but 25% of these patients develop subsequent aneurysmal dilatation of the thoracic aorta. This study aimed at gaining more detailed knowledge of the flow phenomena associated with this condition. Morphological features and flow patterns in a dissected aortic segment of a presurgery type B dissection patient were analyzed based on computed tomography images acquired from the patient. Computational simulations of blood flow in the patient-specific model were performed by employing a correlation-based transitional version of Menter's hybrid k-epsilon/k-omega shear stress transport turbulence model implemented in ANSYS CFX 11. Our results show that the dissected aorta is dominated by locally highly disturbed, and possibly turbulent, flow with strong recirculation. A significant proportion (about 80%) of the aortic flow enters the false lumen, which may further increase the dilatation of the aorta. High values of wall shear stress have been found around the tear on the true lumen wall, perhaps increasing the likelihood of expanding the tear. Turbulence intensity in the tear region reaches a maximum of 70% at midsystolic deceleration phase. Incorporating the non-Newtonian behavior of blood into the same transitional flow model has yielded a slightly lower peak wall shear stress and higher maximum turbulence intensity without causing discernible changes to the distribution patterns. Comparisons between the laminar and turbulent flow simulations show a qualitatively similar distribution of wall shear stress but a significantly higher magnitude with the transitional turbulence model.

CXCR6 promotes atherosclerosis by supporting T-cell homing, interferon-gamma production, and macrophage accumulation in the aortic wall.

PubMed

Galkina, Elena; Harry, Brian L; Ludwig, Andreas; Liehn, Elisa A; Sanders, John M; Bruce, Anthony; Weber, Christian; Ley, Klaus

2007-10-16

T lymphocytes are thought to be important in atherosclerosis, but very little is known about the mechanisms of lymphocyte recruitment into atherosclerosis-prone aortas. In this study we tested the hypothesis that CXCR6, a chemokine receptor that is expressed on a subset of CD4+ T helper 1 cells and natural killer T cells, is involved in lymphocyte homing into the aortic wall and modulates the development and progression of atherosclerosis. To investigate the role of CXCR6 in the development and progression of atherosclerosis, we bred CXCR6-deficient (CXCR6(GFP/GFP)) mice with apolipoprotein E-deficient (ApoE(-/-)) mice. We found that CXCR6(GFP/GFP)/ApoE(-/-) mice fed a Western diet for 17 weeks or a chow diet for 56 weeks had decreased atherosclerosis compared with ApoE(-/-) controls. Flow cytometry analysis of the aortas from CXCR6(GFP/GFP)/ApoE(-/-) mice showed that the reduction of atherosclerosis was accompanied by a decreased percentage of CXCR6+ T cells within the aortas. Short-term homing experiments demonstrated that CXCR6 is involved in the recruitment of CXCR6+ leukocytes into the atherosclerosis-prone aortic wall. The reduced percentage of CXCR6+ T cells within the aortas resulted in significantly diminished production of interferon-gamma and reduction of CD11b+/CD68+ macrophages in the aorta. These data provide evidence for a proatherosclerotic role of CXCR6. Absence of CXCR6 alters the recruitment of CXCR6+ leukocytes and modulates the local immune response within the aortic wall.

A Structural Finite Element Model for Lamellar Unit of Aortic Media Indicates Heterogeneous Stress Field After Collagen Recruitment

PubMed Central

Thunes, James R.; Pal, Siladitya; Fortunato, Ronald N.; Phillippi, Julie A.; Gleason, Thomas G.; Vorp, David A.; Maiti, Spandan

2016-01-01

Incorporation of collagen structural information into the study of biomechanical behavior of ascending thoracic aortic (ATA) wall tissue should provide better insight into the pathophysiology of ATA. Structurally motivated constitutive models that include fiber dispersion and recruitment can successfully capture overall mechanical response of the arterial wall tissue. However, these models cannot examine local microarchitectural features of the collagen network, such as the effect of fiber disruptions and interaction between fibrous and non-fibrous components, which may influence emergent biomechanical properties of the tissue. Motivated by this need, we developed a finite element based three-dimensional structural model of the lamellar units of the ATA media that directly incorporates the collagen fiber microarchitecture. The fiber architecture was computer generated utilizing network features, namely fiber orientation distribution, intersection density and areal concentration, obtained from image analysis of multiphoton microscopy images taken from human aneurysmal ascending thoracic aortic media specimens with bicuspid aortic valve (BAV) phenotype. Our model reproduces the typical J-shaped constitutive response of the aortic wall tissue. We found that the stress state in the non-fibrous matrix was homogeneous until the collagen fibers were recruited, but became highly heterogeneous after that event. The degree of heterogeneity was dependent upon local network architecture with high stresses observed near disrupted fibers. The magnitude of non-fibrous matrix stress at higher stretch levels was negatively correlated with local fiber density. The localized stress concentrations, elucidated by this model, may be a factor in the degenerative changes in aneurysmal ATA tissue. PMID:27113538

Hybrid ECG-gated versus non-gated 512-slice CT angiography of the aorta and coronary artery: image quality and effect of a motion correction algorithm.

PubMed

Lee, Ji Won; Kim, Chang Won; Lee, Geewon; Lee, Han Cheol; Kim, Sang-Pil; Choi, Bum Sung; Jeong, Yeon Joo

2018-02-01

Background Using the hybrid electrocardiogram (ECG)-gated computed tomography (CT) technique, assessment of entire aorta, coronary arteries, and aortic valve can be possible using single-bolus contrast administration within a single acquisition. Purpose To compare the image quality of hybrid ECG-gated and non-gated CT angiography of the aorta and evaluate the effect of a motion correction algorithm (MCA) on coronary artery image quality in a hybrid ECG-gated aorta CT group. Material and Methods In total, 104 patients (76 men; mean age = 65.8 years) prospectively randomized into two groups (Group 1 = hybrid ECG-gated CT; Group 2 = non-gated CT) underwent wide-detector array aorta CT. Image quality, assessed using a four-point scale, was compared between the groups. Coronary artery image quality was compared between the conventional reconstruction and motion correction reconstruction subgroups in Group 1. Results Group 1 showed significant advantages over Group 2 in aortic wall, cardiac chamber, aortic valve, coronary ostia, and main coronary arteries image quality (all P < 0.001). All Group 1 patients had diagnostic image quality of the aortic wall and left ostium. The MCA significantly improved the image quality of the three main coronary arteries ( P < 0.05). Moreover, per-vessel interpretability improved from 92.3% to 97.1% with the MCA ( P = 0.013). Conclusion Hybrid ECG-gated CT significantly improved the heart and aortic wall image quality and the MCA can further improve the image quality and interpretability of coronary arteries.

Two C-C Family Chemokines, Eotaxin and RANTES, Are Novel Independent Plasma Biomarkers for Abdominal Aortic Aneurysm.

PubMed

Jones, Gregory T; Phillips, L Victoria; Williams, Michael J A; van Rij, Andre M; Kabir, Tasnuva D

2016-04-28

Inflammation of the aortic wall is recognised as a key pathogenesis of abdominal aortic aneurysm (AAA). This study was undertaken to determine whether inflammatory cytokines could be used as biomarkers for the presence of AAA. Tissue profiles of 27 inflammatory cytokine were examined in AAA (n=14) and nonaneurysmal (n=14) aortic tissues. Three cytokines, regulated upon activation normally T-cell expressed and secreted (RANTES), eotaxin, and macrophage inflammatory protein 1 beta (MIP-1b), had increased expression in AAA, particularly within the adventitial layer of the aortic wall. Basic fibroblast growth factor (bFGF) had reduced expression in all layers of the AAA wall. Examination of the circulating plasma profiles of AAA (n=442) and AAA-free controls (n=970) suggested a (risk factor adjusted) AAA-association with eotaxin, RANTES, and high sensitivity C-reactive protein (hsCRP). A plasma inflammatory cytokine score, calculated using these three markers, suggested a strong risk association with AAA (odds ratio, 4.8; 95% CI, 3.5-6.7; P<0.0001), independent of age, sex, history of ischemic heart disease, and smoking. Contrary to reports suggesting a distinct T helper 2-associated inflammatory profile in AAA, this current study suggests a more-generalized pattern of inflammation, albeit with some potentially distinct features, including elevated plasma eotaxin and decreased plasma RANTES. In combination with hsCRP, these markers may have potential utility as AAA biomarkers. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Impact of isotropic constitutive descriptions on the predicted peak wall stress in abdominal aortic aneurysms.

PubMed

Man, V; Polzer, S; Gasser, T C; Novotny, T; Bursa, J

2018-03-01

Biomechanics-based assessment of Abdominal Aortic Aneurysm (AAA) rupture risk has gained considerable scientific and clinical momentum. However, computation of peak wall stress (PWS) using state-of-the-art finite element models is time demanding. This study investigates which features of the constitutive description of AAA wall are decisive for achieving acceptable stress predictions in it. Influence of five different isotropic constitutive descriptions of AAA wall is tested; models reflect realistic non-linear, artificially stiff non-linear, or artificially stiff pseudo-linear constitutive descriptions of AAA wall. Influence of the AAA wall model is tested on idealized (n=4) and patient-specific (n=16) AAA geometries. Wall stress computations consider a (hypothetical) load-free configuration and include residual stresses homogenizing the stresses across the wall. Wall stress differences amongst the different descriptions were statistically analyzed. When the qualitatively similar non-linear response of the AAA wall with low initial stiffness and subsequent strain stiffening was taken into consideration, wall stress (and PWS) predictions did not change significantly. Keeping this non-linear feature when using an artificially stiff wall can save up to 30% of the computational time, without significant change in PWS. In contrast, a stiff pseudo-linear elastic model may underestimate the PWS and is not reliable for AAA wall stress computations. Copyright © 2018 IPEM. Published by Elsevier Ltd. All rights reserved.

The interactions between bloodstream and vascular structure on aortic dissecting aneurysmal model: A numerical study

NASA Astrophysics Data System (ADS)

Chen, Zeng-Sheng; Fan, Zhan-Ming; Zhang, Xi-Wen

2013-06-01

Stent-graft implantation is an important means of clinical treatment for aortic dissecting aneurysm (ADA). However, researches on fluid dynamics effects of stent were rare. Computer simulation was used to investigate the interactions between bloodstream and vascular structure in a stented ADA, which endures the periodic pulse velocity and pressure. We obtained and analyzed the flow velocity distribution, the wall displacement and wall stress in the ADA. By comparing the different results between a non-stented and a stented ADA, we found that the insertion of a vascular graft can make the location of maximum stress and displacement move from the aneurysm lumen wall to the artery wall, accompanied with a greatly decrease in value. These results imply that the placement of a stent-graft of any kind to occlude ADA will result in a decreased chance of rupture.

The Relationship Between Surface Curvature and Abdominal Aortic Aneurysm Wall Stress.

PubMed

de Galarreta, Sergio Ruiz; Cazón, Aitor; Antón, Raúl; Finol, Ender A

2017-08-01

The maximum diameter (MD) criterion is the most important factor when predicting risk of rupture of abdominal aortic aneurysms (AAAs). An elevated wall stress has also been linked to a high risk of aneurysm rupture, yet is an uncommon clinical practice to compute AAA wall stress. The purpose of this study is to assess whether other characteristics of the AAA geometry are statistically correlated with wall stress. Using in-house segmentation and meshing algorithms, 30 patient-specific AAA models were generated for finite element analysis (FEA). These models were subsequently used to estimate wall stress and maximum diameter and to evaluate the spatial distributions of wall thickness, cross-sectional diameter, mean curvature, and Gaussian curvature. Data analysis consisted of statistical correlations of the aforementioned geometry metrics with wall stress for the 30 AAA inner and outer wall surfaces. In addition, a linear regression analysis was performed with all the AAA wall surfaces to quantify the relationship of the geometric indices with wall stress. These analyses indicated that while all the geometry metrics have statistically significant correlations with wall stress, the local mean curvature (LMC) exhibits the highest average Pearson's correlation coefficient for both inner and outer wall surfaces. The linear regression analysis revealed coefficients of determination for the outer and inner wall surfaces of 0.712 and 0.516, respectively, with LMC having the largest effect on the linear regression equation with wall stress. This work underscores the importance of evaluating AAA mean wall curvature as a potential surrogate for wall stress.

Aortic valve stenosis and aortic diameters determine the extent of increased wall shear stress in bicuspid aortic valve disease.

PubMed

Farag, Emile S; van Ooij, Pim; Planken, R Nils; Dukker, Kayleigh C P; de Heer, Frederiek; Bouma, Berto J; Robbers-Visser, Danielle; Groenink, Maarten; Nederveen, Aart J; de Mol, Bas A J M; Kluin, Jolanda; Boekholdt, S Matthijs

2018-02-16

Use of 4-dimensional flow magnetic resonance imaging (4D-flow MRI) derived wall shear stress (WSS) heat maps enables identification of regions in the ascending aorta with increased WSS. These regions are subject to dysregulation of the extracellular matrix and elastic fiber degeneration, which is associated with aortic dilatation and dissection. To evaluate the effect of the presence of aortic valve stenosis and the aortic diameter on the peak WSS and surface area of increased WSS in the ascending aorta. Prospective. In all, 48 bicuspid aortic valve (BAV) patients (38.1 ± 12.4 years) and 25 age- and gender-matched healthy individuals. Time-resolved 3D phase contrast MRI with three-directional velocity encoding at 3.0T. Peak systolic velocity, WSS, and aortic diameters were assessed in the ascending aorta and 3D heat maps were used to identify regions with elevated WSS. Comparisons between groups were performed by t-tests. Correlations were investigated by univariate and multivariate regression analysis. Elevated WSS was present in 15 ± 11% (range; 1-35%) of the surface area of the ascending aorta of BAV patients with aortic valve stenosis (AS) (n = 10) and in 6 ± 8% (range; 0-31%) of the ascending aorta of BAV patients without AS (P = 0.005). The mid-ascending aortic diameter negatively correlated with the peak ascending aortic WSS (R = -0.413, P = 0.004) and the surface area of elevated WSS (R = -0.419, P = 0.003). Multivariate linear regression analysis yielded that the height of peak WSS and the amount of elevated WSS depended individually on the presence of aortic valve stenosis and the diameter of the ascending aorta. The extent of increased WSS in the ascending aorta of BAV patients depends on the presence of aortic valve stenosis and aortic dilatation and is most pronounced in the presence of AS and a nondilated ascending aorta. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. © 2018 The Authors Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Computer model analysis of the radial artery pressure waveform.

PubMed

Schwid, H A; Taylor, L A; Smith, N T

1987-10-01

Simultaneous measurements of aortic and radial artery pressures are reviewed, and a model of the cardiovascular system is presented. The model is based on resonant networks for the aorta and axillo-brachial-radial arterial system. The model chosen is a simple one, in order to make interpretation of the observed relationships clear. Despite its simplicity, the model produces realistic aortic and radial artery pressure waveforms. It demonstrates that the resonant properties of the arterial wall significantly alter the pressure waveform as it is propagated from the aorta to the radial artery. Although the mean and end-diastolic radial pressures are usually accurate estimates of the corresponding aortic pressures, the systolic pressure at the radial artery is often much higher than that of the aorta due to overshoot caused by the resonant behavior of the radial artery. The radial artery dicrotic notch is predominantly dependent on the axillo-brachial-radial arterial wall properties, rather than on the aortic valve or peripheral resistance. Hence the use of the radial artery dicrotic notch as an estimate of end systole is unreliable. The rate of systolic upstroke, dP/dt, of the radial artery waveform is a function of many factors, making it difficult to interpret. The radial artery waveform usually provides accurate estimates for mean and diastolic aortic pressures; for all other measurements it is an inadequate substitute for the aortic pressure waveform. In the presence of low forearm peripheral resistance the mean radial artery pressure may significantly underestimate the mean aortic pressure, as explained by a voltage divider model.

Fluid-structure interaction in abdominal aortic aneurysms: Structural and geometrical considerations

NASA Astrophysics Data System (ADS)

Mesri, Yaser; Niazmand, Hamid; Deyranlou, Amin; Sadeghi, Mahmood Reza

2015-08-01

Rupture of the abdominal aortic aneurysm (AAA) is the result of the relatively complex interaction of blood hemodynamics and material behavior of arterial walls. In the present study, the cumulative effects of physiological parameters such as the directional growth, arterial wall properties (isotropy and anisotropy), iliac bifurcation and arterial wall thickness on prediction of wall stress in fully coupled fluid-structure interaction (FSI) analysis of five idealized AAA models have been investigated. In particular, the numerical model considers the heterogeneity of arterial wall and the iliac bifurcation, which allows the study of the geometric asymmetry due to the growth of the aneurysm into different directions. Results demonstrate that the blood pulsatile nature is responsible for emerging a time-dependent recirculation zone inside the aneurysm, which directly affects the stress distribution in aneurismal wall. Therefore, aneurysm deviation from the arterial axis, especially, in the lateral direction increases the wall stress in a relatively nonlinear fashion. Among the models analyzed in this investigation, the anisotropic material model that considers the wall thickness variations, greatly affects the wall stress values, while the stress distributions are less affected as compared to the uniform wall thickness models. In this regard, it is confirmed that wall stress predictions are more influenced by the appropriate structural model than the geometrical considerations such as the level of asymmetry and its curvature, growth direction and its extent.

Natural history of severe aortic stenosis: Diastolic wall strain as a novel prognostic marker.

PubMed

Obasare, Edinrin; Bhalla, Vikas; Gajanana, Deepakraj; Rodriguez Ziccardi, Mary; Codolosa, Jose N; Figueredo, Vincent M; Morris, Dennis Lynn; Pressman, Gregg S

2017-04-01

Diastolic wall strain (DWS) has been proposed as a simple noninvasive measure of left ventricular (LV) stiffness. This study investigated DWS as a possible predictor of mortality in severe aortic stenosis (AS). 138 patients with severe AS (indexed aortic valve area [AVA]<0.6 cm 2 /m 2 ) and normal ejection fraction (>55%) were included. 52 patients (38%) had aortic valve interventions or poor image quality (n=5) and were excluded leaving 86 in the study group (84±8 years, 70% female, 69% African American). DWS was defined as (LVPWs-LVPWd)/LVPWs where LVPWs=left ventricular posterior wall thickness in systole and LVPWd=left ventricular wall thickness in diastole. Follow-up extended 2.0±1.9 years (median 1.6 years). Mean DWS for the group was 0.21±0.11 (normal=0.4±0.07). In patients who died, DWS was significantly lower than in survivors (0.18±0.09 vs 0.24±0.11, P=.02). By contrast, traditional measures of diastolic dysfunction did not predict death. Regression analysis showed DWS predicted death even after adjusting for age, sex, race, indexed AVA, symptoms (angina, shortness of breath, dizziness, syncope), and clinical factors (creatinine, smoking, diabetes, hypertension, hyperlipidemia) (HR 2.5 [95% CI 1.02-5.90], P<.05). The best cutoff value for DWS of 0.25 had a sensitivity of 42% and specificity of 83% for predicting death. DWS is an independent predictor of all-cause mortality in patients with severe AS, even after accounting for traditional clinical and echocardiographic parameters. © 2017, Wiley Periodicals, Inc.

TGFβ (Transforming Growth Factor-β) Blockade Induces a Human-Like Disease in a Nondissecting Mouse Model of Abdominal Aortic Aneurysm.

PubMed

Lareyre, Fabien; Clément, Marc; Raffort, Juliette; Pohlod, Stefanie; Patel, Meghana; Esposito, Bruno; Master, Leanne; Finigan, Alison; Vandestienne, Marie; Stergiopulos, Nikolaos; Taleb, Soraya; Trachet, Bram; Mallat, Ziad

2017-11-01

Current experimental models of abdominal aortic aneurysm (AAA) do not accurately reproduce the major features of human AAA. We hypothesized that blockade of TGFβ (transforming growth factor-β) activity-a guardian of vascular integrity and immune homeostasis-would impair vascular healing in models of nondissecting AAA and would lead to sustained aneurysmal growth until rupture. Here, we test this hypothesis in the elastase-induced AAA model in mice. We analyze AAA development and progression using ultrasound in vivo, synchrotron-based ultrahigh resolution imaging ex vivo, and a combination of biological, histological, and flow cytometry-based cellular and molecular approaches in vitro. Systemic blockade of TGFβ using a monoclonal antibody induces a transition from a self-contained aortic dilatation to a model of sustained aneurysmal growth, associated with the formation of an intraluminal thrombus. AAA growth is associated with wall disruption but no medial dissection and culminates in fatal transmural aortic wall rupture. TGFβ blockade enhances leukocyte infiltration both in the aortic wall and the intraluminal thrombus and aggravates extracellular matrix degradation. Early blockade of IL-1β or monocyte-dependent responses substantially limits AAA severity. However, blockade of IL-1β after disease initiation has no effect on AAA progression to rupture. Endogenous TGFβ activity is required for the healing of AAA. TGFβ blockade may be harnessed to generate new models of AAA with better relevance to the human disease. We expect that the new models will improve our understanding of the pathophysiology of AAA and will be useful in the identification of new therapeutic targets. © 2017 American Heart Association, Inc.

Increasing the feasibility of minimally invasive procedures in type A aortic dissections: a framework for segmentation and quantification.

PubMed

Morariu, Cosmin Adrian; Terheiden, Tobias; Dohle, Daniel Sebastian; Tsagakis, Konstantinos; Pauli, Josef

2016-02-01

Our goal is to provide precise measurements of the aortic dimensions in case of dissection pathologies. Quantification of surface lengths and aortic radii/diameters together with the visualization of the dissection membrane represents crucial prerequisites for enabling minimally invasive treatment of type A dissections, which always also imply the ascending aorta. We seek a measure invariant to luminance and contrast for aortic outer wall segmentation. Therefore, we propose a 2D graph-based approach using phase congruency combined with additional features. Phase congruency is extended to 3D by designing a novel conic directional filter and adding a lowpass component to the 3D Log-Gabor filterbank for extracting the fine dissection membrane, which separates the true lumen from the false one within the aorta. The result of the outer wall segmentation is compared with manually annotated axial slices belonging to 11 CTA datasets. Quantitative assessment of our novel 2D/3D membrane extraction algorithms has been obtained for 10 datasets and reveals subvoxel accuracy in all cases. Aortic inner and outer surface lengths, determined within 2 cadaveric CT datasets, are validated against manual measurements performed by a vascular surgeon on excised aortas of the body donors. This contribution proposes a complete pipeline for segmentation and quantification of aortic dissections. Validation against ground truth of the 3D contour lengths quantification represents a significant step toward custom-designed stent-grafts.

Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data.

PubMed

Vasan, Ramachandran S; Glazer, Nicole L; Felix, Janine F; Lieb, Wolfgang; Wild, Philipp S; Felix, Stephan B; Watzinger, Norbert; Larson, Martin G; Smith, Nicholas L; Dehghan, Abbas; Grosshennig, Anika; Schillert, Arne; Teumer, Alexander; Schmidt, Reinhold; Kathiresan, Sekar; Lumley, Thomas; Aulchenko, Yurii S; König, Inke R; Zeller, Tanja; Homuth, Georg; Struchalin, Maksim; Aragam, Jayashri; Bis, Joshua C; Rivadeneira, Fernando; Erdmann, Jeanette; Schnabel, Renate B; Dörr, Marcus; Zweiker, Robert; Lind, Lars; Rodeheffer, Richard J; Greiser, Karin Halina; Levy, Daniel; Haritunians, Talin; Deckers, Jaap W; Stritzke, Jan; Lackner, Karl J; Völker, Uwe; Ingelsson, Erik; Kullo, Iftikhar; Haerting, Johannes; O'Donnell, Christopher J; Heckbert, Susan R; Stricker, Bruno H; Ziegler, Andreas; Reffelmann, Thorsten; Redfield, Margaret M; Werdan, Karl; Mitchell, Gary F; Rice, Kenneth; Arnett, Donna K; Hofman, Albert; Gottdiener, John S; Uitterlinden, Andre G; Meitinger, Thomas; Blettner, Maria; Friedrich, Nele; Wang, Thomas J; Psaty, Bruce M; van Duijn, Cornelia M; Wichmann, H-Erich; Munzel, Thomas F; Kroemer, Heyo K; Benjamin, Emelia J; Rotter, Jerome I; Witteman, Jacqueline C; Schunkert, Heribert; Schmidt, Helena; Völzke, Henry; Blankenberg, Stefan

2009-07-08

Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n = 4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10(-7) to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort. Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size. In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1% of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance). We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease.

Biomechanical analysis of wrapping of the moderately dilated ascending aorta.

PubMed

Plonek, Tomasz; Rylski, Bartosz; Dumanski, Andrzej; Siedlaczek, Przemyslaw; Kustrzycki, Wojciech

2015-08-01

External wrapping is a surgical method performed to prevent the dilatation of the aorta and to decrease the risk of its dissection and rupture. However, it is also believed to cause degeneration of the aortic wall. A biomechanical analysis was thus performed to assess the stress of the aortic wall subjected to external wrapping. A stress analysis using the finite elements method was carried out on three models: a non-dilated aorta, a moderately dilated aorta and a wrapped aorta. The models were subjected to a pulsatile flow (120/80 mmHg) and a systolic aortic annulus motion of 11 mm. The finite elements analysis showed that the stress exerted on the outer surface of the ascending aorta in the wrapping model (0.05-0.8 MPa) was similar to that observed in the normal aorta (0.03-0.7 MPa) and was lower than in the model of a moderately dilated aorta (0.06-1.4 MPa). The stress on the inner surface of the ascending aorta ranged from 0.2 MPa to 0.4 MPa in the model of the normal aorta, from 0.3 to 1.3 MPa in the model of the dilated aorta and from 0.05 MPa to 0.4 MPa in the wrapping model. The results of this study suggest that the aortic wall is subjected to similar stress following a wrapping procedure to the one present in the normal aorta.

Chasing the reflected wave back into the heart: a new hypothesis while the jury is still out

PubMed Central

Codreanu, Ion; Robson, Matthew D; Rider, Oliver J; Pegg, Tammy J; Jung, Bernd A; Dasanu, Constantin A; Clarke, Kieran; Holloway, Cameron J

2011-01-01

Background: Arterial stiffness directly influences cardiac function and is independently associated with cardiovascular risk. However, the influence of the aortic reflected pulse pressure wave on left ventricular function has not been well characterized. The aim of this study was to obtain detailed information on regional ventricular wall motion patterns corresponding to the propagation of the reflected aortic wave on ventricular segments. Methods: Left ventricular wall motion was investigated in a group of healthy volunteers (n = 14, age 23 ± 3 years), using cardiac magnetic resonance navigator-gated tissue phase mapping. The left ventricle was divided into 16 segments and regional wall motion was studied in high temporal detail. Results: Corresponding to the expected timing of the reflected aortic wave reaching the left ventricle, a characteristic “notch” of regional myocardial motion was seen in all radial, circumferential, and longitudinal velocity graphs. This notch was particularly prominent in septal segments adjacent to the left ventricular outflow tract on radial velocity graphs and in anterior and posterior left ventricular segments on circumferential velocity graphs. Similarly, longitudinal velocity graphs demonstrated a brief deceleration in the upward recoil motion of the entire ventricle at the beginning of diastole. Conclusion: These results provide new insights into the possible influence of the reflected aortic waves on ventricular segments. Although the association with the reflected wave appears to us to be unambiguous, it represents a novel research concept, and further studies enabling the actual recording of the pulse wave are required. PMID:21731888

Aortic operation after previous coronary artery bypass grafting: management of patent grafts for myocardial protection.

PubMed

Nakajima, Masato; Tsuchiya, Koji; Fukuda, Shoji; Morimoto, Hironobu; Mitsumori, Yoshitaka; Kato, Kaori

2006-04-01

Aortic surgery for progressive aortic valve disease or aortic aneurysm after previous coronary artery bypass grafting (CABG) is a challenging procedure. We report the outcome of aortic reoperation after previous CABG and evaluate our management of patent grafts and our methods for obtaining myocardial protection. From February 2001 to July 2003, 6 patients with progressive aortic valve disease and aneurysm of the thoracic aorta were operated on. The group comprised 3 men and 3 women with a mean age of 67.6 years. There were 4 patients with an aneurysm of the aortic arch, 1 with chronic ascending aortic dissection, and 1 with progressive aortic valve stenosis. The interval between previous CABG and aortic surgery was 74.0 +/- 44.2 months. All reoperations were performed via median resternotomy. Myocardial protection was obtained by hypothermic perfusion of patent in-situ arterial grafts following cold-blood cardioplegia administration via the aortic root under aortic cross clamping. The operative procedure was aortic arch replacement in 4 patients, ascending aortic replacement with double CABG in 1, and aortic valve replacement in 1. All patients survived the reoperation. Postoperative maximum creatine kinase-MB was 49.2 +/- 29.8 and no new Q-waves occurred in the electrocardiogram nor were any new wall motion abnormalities recognized on echocardiography. There were no late deaths during a follow-up of 30.7 months. Reoperative aortic procedures after CABG can be performed safely with myocardial protection via hypothermic perfusion of a patent in-situ arterial graft.

Adipocytes and abdominal aortic aneurysm: Putative potential role of adipocytes in the process of AAA development.

PubMed

Kugo, Hirona; Moriyama, Tatsuya; Zaima, Nobuhiro

2018-01-15

Background Adipose tissue plays a role in the storage of excess energy as triglycerides (TGs). Excess fat accumulation causes various metabolic and cardiovascular diseases. It has been reported that ectopic fat deposition and excess TG accumulation in non-adipose tissue might be important predictors of cardiometabolic and vascular risk. For example, ectopic fat in perivascular tissue promotes atherosclerotic plaque formation in the arterial wall. Objective Recently, it has been reported that ectopic fat (adipocyte) in the vascular wall of an abdominal aortic aneurysm (AAA) is present in both human and experimental animal models. The pathological significance of adipocytes in the AAA wall has not been fully understood. In this review, we summarized the functions of adipocytes and discussed potential new drugs that target vascular adipocytes for AAA treatment. Result Previous studies suggest that adipocytes in vascular wall play an important role in the development of AAA. Conclusion Adipocytes in the vascular wall could be novel targets for the development of AAA therapeutic drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Relationship Between Pulsatile Flow Impingement and Intraluminal Thrombus Deposition in Abdominal Aortic Aneurysms.

PubMed

Lozowy, Richard J; Kuhn, David C S; Ducas, Annie A; Boyd, April J

2017-03-01

Direct numerical simulations were performed on four patient-specific abdominal aortic aneurysm (AAA) geometries and the resulting pulsatile blood flow dynamics were compared to aneurysm shape and correlated with intraluminal thrombus (ILT) deposition. For three of the cases, turbulent vortex structures impinged/sheared along the anterior wall and along the posterior wall a zone of recirculating blood formed. Within the impingement region the AAA wall was devoid of ILT and remote to this region there was an accumulation of ILT. The high wall shear stress (WSS) caused by the impact of vortexes is thought to prevent the attachment of ILT. WSS from impingement is comparable to peak-systolic WSS in a normal-sized aorta and therefore may not damage the wall. Expansion occurred to a greater extent in the direction of jet impingement and the wall-normal force from the continuous impact of vortexes may contribute to expansion. It was shown that the impingement region has low oscillatory shear index (OSI) and recirculation zones can have either low or high OSI. No correlation could be identified between OSI and ILT deposition since different flow dynamics can have similar OSI values.

Saccular aortic aneurysm that resembled a mediastinal neoplasm

PubMed Central

Nose, Naohiro; Kataoka, Hiroumi; Hamada, Masakatsu; Kosako, Yukio; Matsuno, Yasuji; Ishii, Takahiro

2012-01-01

INTRODUCTION Saccular aortic arch aneurysms in unusual sites may be misdiagnosed as a neoplasm. We present the case of a rare saccular aortic arch aneurysm between trachea and esophagus that resembled a mediastinal neoplasm in the preoperative findings. PRESENTATION OF CASE A 63-year-old male with an abnormal mediastinal shadow on chest X-ray was referred to the hospital. An axial plain computed tomogram of the chest revealed mediastinal soft tissue next to the right side of the aortic arch resembling a neoplasm originating from the gap between the trachea and the esophagus. The coronal view constructed by enhanced 64-row multi detector computed tomography revealed the soft tissue was an aneurysm arising from the inner side of the aortic arch. An aortic arch replacement was performed via a median sternotomy. DISCUSSION A thoracic aortic aneurysm sometimes behaves like a mediastinal neoplasm. The multiple cross-sectional image from multidetector computed tomography was useful for the correct diagnosis of such an aneurysm. CONCLUSION The possibility of an aneurysm should be considered whenever a mass in contact with the aortic wall is identified. PMID:22995656

Multimodal optical measurement in vitro of surface deformations and wall thickness of the pressurized aortic arch

NASA Astrophysics Data System (ADS)

Genovese, Katia; Humphrey, Jay D.

2015-04-01

Computational modeling of arterial mechanics continues to progress, even to the point of allowing the study of complex regions such as the aortic arch. Nevertheless, most prior studies assign homogeneous and isotropic material properties and constant wall thickness even when implementing patient-specific luminal geometries obtained from medical imaging. These assumptions are not due to computational limitations, but rather to the lack of spatially dense sets of experimental data that describe regional variations in mechanical properties and wall thickness in such complex arterial regions. In this work, we addressed technical challenges associated with in vitro measurement of overall geometry, full-field surface deformations, and regional wall thickness of the porcine aortic arch in its native anatomical configuration. Specifically, we combined two digital image correlation-based approaches, standard and panoramic, to track surface geometry and finite deformations during pressurization, with a 360-deg fringe projection system to contour the outer and inner geometry. The latter provided, for the first time, information on heterogeneous distributions of wall thickness of the arch and associated branches in the unloaded state. Results showed that mechanical responses vary significantly with orientation and location (e.g., less extensible in the circumferential direction and with increasing distance from the heart) and that the arch exhibits a nearly linear increase in pressure-induced strain up to 40%, consistent with other findings on proximal porcine aortas. Thickness measurements revealed strong regional differences, thus emphasizing the need to include nonuniform thicknesses in theoretical and computational studies of complex arterial geometries.

A numerical framework for studying the biomechanical behavior of abdominal aortic aneurysm

NASA Astrophysics Data System (ADS)

Jalalahmadi, Golnaz; Linte, Cristian; Helguera, María.

2017-03-01

Abdominal aortic aneurysm (AAA) is known as a leading cause of death in the United States. AAA is an abnormal dilation of the aorta, which usually occurs below the renal arteries and causes an expansion at least 1.5 times its normal diameter. It has been shown that biomechanical parameters of the aortic tissue coupled with a set of specific geometric parameters characterizing the vessel expansion, affect the risk of aneurysm rupture. Here, we developed a numerical framework that incorporates both biomechanical and geometrical factors to study the behavior of abdominal aortic aneurysm. Our workflow enables the extraction of the aneurysm geometry from both clinical quality, as well as low-resolution MR images. We used a two-parameter, hyper-elastic, isotropic, incompressible material to model the vessel tissue. Our numerical model was tested using both synthetic and mouse data and we evaluated the effects of the geometrical and biomechanical properties on the developed peak wall stress. In addition, we performed several parameter sensitivity studies to investigate the effect of different factors affecting the AAA and its behavior and rupture. Lastly, relationships between different geometrical and biomechanical parameters and peak wall stress were determined. These studies help us better understand vessel tissue response to various loading, geometry and biomechanics conditions, and we plan to further correlate these findings with the pathophysiological conditions from a patient population diagnosed with abdominal aortic aneurysms.

Aortic Wall Extracellular Matrix Proteins Correlate with Syntax Score in Patients Undergoing Coronary Artery Bypass Surgery

PubMed Central

Chiong, Terri; Cheow, Esther S. H.; Woo, Chin C.; Lin, Xiao Y.; Khin, Lay W.; Lee, Chuen N.; Hartman, Mikael; Sze, Siu K.; Sorokin, Vitaly A.

2016-01-01

Aims: The SYNTAX score correlate with major cardiovascular events post-revascularization, although the histopathological basis is unclear. We aim to evaluate the association between syntax score and extracellular matrix histological characteristics of aortic punch tissue obtained during coronary artery bypass surgery (CABG). This analysis compares coronary artery bypass surgery patients with High and Low syntax score which were followed up for one year period. Methods and Results: Patients with High (score ≥ 33, (n=77)) and Low Syntax Scores (score ≤ 22, (n=71)) undergoing elective CABG were recruited prospectively. Baseline clinical characteristics and surgical risks were well matched. At 1 year, EMACCE (Sum of cardiovascular death, stroke, congestive cardiac failure, and limb, gut and myocardial ischemia) was significantly elevated in the High syntax group (P=0.022). Mass spectrometry (MS)-based quantitative iTRAQ proteomic results validated on independent cohort by immunohistochemistry (IHC) revealed that the High syntax group had significantly upraised Collagen I (P<0.0001) and Elastin (P<0.0001) content in ascending aortic wall. Conclusion: This study shows that aortic extracellular matrix (ECM) differ between High and Low syntax groups with up-regulation of Collagen I and Elastin level in High Syntax Score group. This identifies aortic punches collected during CABG as another biomarker source related with atherosclerosis severity and possible clinical outcome. PMID:27347220

The role of jet eccentricity in generating disproportionately elevated transaortic pressure gradients in patients with aortic stenosis.

PubMed

Abbas, Amr E; Franey, Laura M; Lester, Steven; Raff, Gilbert; Gallagher, Michael J; Hanzel, George; Safian, Robert D; Pibarot, Philippe

2015-02-01

In patients with aortic stenosis (AS) and eccentric transaortic flow, greater pressure loss occurs as the jet collides with the aortic wall together with delayed and diminished pressure recovery. This leads to the elevated transaortic valve pressure gradients noted on both Doppler and cardiac catheterization. Such situations may present a diagnostic dilemma where traditional measures of stenosis severity indicate severe AS, while imaging modalities of the aortic valve geometric aortic valve area (GOA) suggest less than severe stenosis. In this study, we present a series of cases exemplifying this clinical dilemma and demonstrate how color M-mode, 2D and 3D transthoracic (TTE) and transesophageal (TEE) echocardiography, cardiac computed tomography angiography (CTA), and magnetic resonance imaging (MRI), may be used to resolve such discrepancies. © 2014, Wiley Periodicals, Inc.

Advances in aortic disease management: a year in review.

PubMed

Garg, Vinay; Ouzounian, Maral; Peterson, Mark D

2016-03-01

The medical and surgical management of aortic disease is continually changing in search for improved outcomes. Our objective is to highlight recent advances in a few select areas pertaining to aortic disease and aortic surgery: the genetics of aortopathy, medical therapy of aortic aneurysms, advances in cardiac imaging, and operative strategies for the aortic arch. As our understanding of the genetic basis for aortopathy continues to improve, routine genetic testing may be of value in assessing patients with genetically triggered forms of aortic disease. With regard to medical advances, treating patients with Marfan syndrome with either losartan or atenolol at an earlier stage in their disease course improves outcomes. In addition, novel imaging indices such as wall shear stress and aortic stiffness assessed by MRI may become useful markers of aortopathy and warrant further study. With regard to the optimal technique for cerebral perfusion in aortic arch surgery, high-quality data are still lacking. Finally, in patients with complex, multilevel aortic disease, the frozen elephant trunk is a viable single-stage option compared with the conventional elephant trunk, although with an increased risk for spinal cord injury. Based on recent advances, continued studies in genetics, cardiac imaging, and surgical trials will further elucidate the etiology of aortopathy and ultimately guide management, both medically and surgically.

Combining two potential causes of metalloproteinase secretion causes abdominal aortic aneurysms in rats: a new experimental model

PubMed Central

Mata, Karina M; Prudente, Paula S; Rocha, Fabio S; Prado, Cibele M; Floriano, Elaine M; Elias, Jorge; Rizzi, Elen; Gerlach, Raquel F; Rossi, Marcos A; Ramos, Simone G

2011-01-01

Progress in understanding the pathophysiology of abdominal aortic aneurysms (AAA) is dependent in part on the development and application of effective animal models that recapitulate key aspects of the disease. The objective was to produce an experimental model of AAA in rats by combining two potential causes of metalloproteinase (MMP) secretion: inflammation and turbulent blood flow. Male Wistar rats were randomly divided in four groups: Injury, Stenosis, Aneurysm and Control (40/group). The Injury group received a traumatic injury to the external aortic wall. The Stenosis group received an extrinsic stenosis at a corresponding location. The Aneurysm group received both the injury and stenosis simultaneously, and the Control group received a sham operation. Animals were euthanized at days 1, 3, 7 and 15. Aorta and/or aneurysms were collected and the fragments were fixed for morphologic, immunohistochemistry and morphometric analyses or frozen for MMP assays. AAAs had developed by day 3 in 60–70% of the animals, reaching an aortic dilatation ratio of more than 300%, exhibiting intense wall remodelling initiated at the adventitia and characterized by an obvious inflammatory infiltrate, mesenchymal proliferation, neoangiogenesis, elastin degradation and collagen deposition. Immunohistochemistry and zymography studies displayed significantly increased expressions of MMP-2 and MMP-9 in aneurysm walls compared to other groups. The haemo-dynamic alterations caused by the stenosis may have provided additional contribution to the MMPs liberation. This new model illustrated that AAA can be multifactorial and confirmed the key roles of MMP-2 and MMP-9 in this dynamic remodelling process. PMID:21039990

Abdominal aortic aneurysms: an autoimmune disease?

PubMed

Jagadesham, Vamshi P; Scott, D Julian A; Carding, Simon R

2008-12-01

Abdominal aortic aneurysms (AAAs) are a multifactorial degenerative vascular disorder. One of the defining features of the pathophysiology of aneurysmal disease is inflammation. Recent developments in vascular and molecular cell biology have increased our knowledge on the role of the adaptive and innate immune systems in the initiation and propagation of the inflammatory response in aortic tissue. AAAs share many features of autoimmune disease, including genetic predisposition, organ specificity and chronic inflammation. Here, this evidence is used to propose that the chronic inflammation observed in AAAs is a consequence of a dysregulated autoimmune response against autologous components of the aortic wall that persists inappropriately. Identification of the molecular and cellular targets involved in AAA formation will allow the development of therapeutic agents for the treatment of AAA.

Mechanism of smart baroreception in the aortic arch

NASA Astrophysics Data System (ADS)

Kember, G. C.; Armour, J. A.; Zamir, M.

2006-09-01

A mechanism is proposed by which the patch of baroreceptors along the inner curvature of the arch of the aorta can sense hemodynamic events occurring downstream from the aortic arch, in the periphery of the arterial tree. Based on a solution of equations governing the elastic movements of the aortic wall, it is shown that the pressure distribution along the patch of baroreceptors has the same functional form as the distribution of strain along the patch. The significance of these findings are discussed, particularly as they relate to the possibility of a neuromechanical basis of essential hypertension.

The effects of hypoxemia on myocardial blood flow during exercise.

PubMed

Paridon, S M; Bricker, J T; Dreyer, W J; Reardon, M; Smith, E O; Porter, C B; Michael, L; Fisher, D J

1989-03-01

We evaluated the adequacy of regional and transmural blood flow during exercise and rapid pacing after 1 wk of hypoxemia. Seven mature mongrel dogs were made hypoxemic (mean O2 saturation = 72.4%) by anastomosis of left pulmonary artery to left atrial appendage. Catheters were placed in the left atrium, right atrium, pulmonary artery, and aorta. Atrial and ventricular pacing wires were placed. An aortic flow probe was placed to measure cardiac output. Ten nonshunted dogs, similarly instrumented, served as controls. Recovery time was approximately 1 wk. Cardiac output, mean aortic pressure, and oxygen saturation were measured at rest, with ventricular pacing, atrial pacing, and with treadmill exercise. Ventricular and atrial pace and exercise were at a heart rate of 200. Right ventricular free wall, left ventricular free wall, and septal blood flow were measured with radionuclide-labeled microspheres. Cardiac output, left atrial blood pressure, and aortic blood pressure were similar between the two groups of dogs in all testing states. Myocardial blood flow was significantly higher in the right and left ventricular free wall in the hypoxemic animals during resting and exercise testing states. Myocardial oxygen delivery was similar between the two groups of animals. Pacing resulted in an increase in myocardial blood flow in the control animals but not the hypoxemic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of the aortoatrial continuity as means of providing left ventricular assist support without entering the ventricle: a feasibility study.

PubMed

Friedman, Paul A; Kushwaha, Sudhir S; Bruce, Charles J; Park, Soon J; Ladewig, Dorothy J; Mikell, Susan B; Johnson, Susan B; Suddendorf, Scott H; Danielsen, Andrew J; Asirvatham, Samuel J

2011-06-01

Left ventricular assist devices (LVADs) are increasingly used to treat patients with refractory heart failure. Current-generation LVADs have major limitations, including the need for open chest surgery, limiting their widespread use. We hypothesized that the aortoatrial continuity could be used as a unique anatomic vantage point for entirely percutaneous LVAD placement. Forty human autopsied hearts were examined to ascertain the presence and define the dimensions of the continuity between the posterior aortic wall and the left atrium. In all cases, a "septum" between the aorta and left atrium was identified. In 3 animal experiments, a custom mechanical shunt was deployed in the wall between the left atrium and noncoronary cusp. With continuous intracardiac ultrasound imaging, and at necropsy, there was no evidence of device dislodgement, pericardial effusion, or aortic or coronary artery trauma noted. It is feasible to use the wall between the aorta and left atrium as an access route for a potentially entirely percutaneous LVAD. Such a system obviates the need for accessing the left ventricle, minimizing complications. In the future, such devices may allow widespread treatment of heart failure, malignant cardiac arrhythmia, and severe aortic and mitral valvular disease. Copyright © 2011 Elsevier Inc. All rights reserved.

Jet length/velocity ratio: a new index for echocardiographic evaluation of chronic aortic regurgitation.

PubMed

Güvenç, Tolga Sinan; Karaçimen, Denizhan; Erer, Hatice Betül; İlhan, Erkan; Sayar, Nurten; Karakuş, Gültekin; Çekirdekçi, Elif; Eren, Mehmet

2015-01-01

Management of aortic regurgitation depends on the assessment for severity. Echocardiography remains as the most widely available tool for evaluation of aortic regurgitation. In this manuscript, we describe a novel parameter, jet length/velocity ratio, for the diagnosis of severe aortic regurgitation. A total of 30 patients with aortic regurgitation were included to this study. Severity of aortic regurgitation was assessed with an aortic regurgitation index incorporating five echocardiographic parameters. Jet length/velocity ratio is calculated as the ratio of maximum jet penetrance to mean velocity of regurgitant flow. Jet length/velocity ratio was significantly higher in patients with severe aortic regurgitation (2.03 ± 0.53) compared to patients with less than severe aortic regurgitation (1.24 ± 0.32, P < 0.001). Correlation of jet length/velocity ratio with aortic regurgitation index was very good (r(2) = 0.86) and correlation coefficient was higher for jet length/velocity ratio compared to vena contracta, jet width/LVOT ratio and pressure half time. For a cutoff value of 1.61, jet length/velocity ratio had a sensitivity of 92% and specificity of 88%, with an AUC value of 0.955. Jet length/velocity ratio is a novel parameter that can be used to assess severity of chronic aortic regurgitation. Main limitation for usage of this novel parameter is jet impringement to left ventricular wall. © 2014, Wiley Periodicals, Inc.

Cardiovascular risk indicators and perceived race/ethnic discrimination in the Dallas Heart Study.

PubMed

Albert, Michelle A; Ravenell, Joseph; Glynn, Robert J; Khera, Amit; Halevy, Nitsan; de Lemos, James A

2008-12-01

The objective of the study was to evaluate the association between race/ethnic (r/e) discrimination and subclinical cardiovascular disease (CVD). Although r/e discrimination is a chronic stressor that might have negative health effects, cardiovascular data related to experiences with discrimination among different r/e groups in the United States remain sparse. Using data from the Dallas Heart Study, we assessed the association between perceived r/e discrimination and traditional CVD risk factors, C-reactive protein (CRP), aortic plaque area and wall thickness, and coronary calcium (CAC) score among black, white, and Hispanic participants. Prevalent CAC was defined as a CAC score > or =10 Agatston units; CRP elevation was defined as > or =3 mg/L. Participants were asked, "Have you ever been discriminated against due to your race/ethnicity? (responses: yes, no, or don't know)". Blacks reported r/e discrimination more frequently than whites or Hispanics (P < .0001). Blacks who reported r/e discrimination were more likely to be college graduates, to have a family history of myocardial infarction, and to be more physically active than blacks who did not report r/e discrimination (each P < .05). Hispanics who reported r/e discrimination had a higher prevalence of smoking (P < .01) and were more likely to be born in the United States. In models that adjusted for traditional CVD risk factors and medication use, we generally found no association between reports of r/e discrimination and aortic wall thickness, aortic plaque area, prevalent CAC, or elevated CRP in any of the r/e groups. Among blacks, stratification by gender and education did not change the observed relationship between perceived r/e discrimination and CAC or CRP. Although perceived r/e discrimination is associated with certain health characteristics that may result in negative health outcomes, in general, we found no association of r/e discrimination with either subclinical atherosclerosis as determined by CAC score, aortic wall thickness and aortic plaque area, or inflammation as assessed by elevated CRP levels.

Fluid, solid and fluid-structure interaction simulations on patient-based abdominal aortic aneurysm models.

PubMed

Kelly, Sinead; O'Rourke, Malachy

2012-04-01

This article describes the use of fluid, solid and fluid-structure interaction simulations on three patient-based abdominal aortic aneurysm geometries. All simulations were carried out using OpenFOAM, which uses the finite volume method to solve both fluid and solid equations. Initially a fluid-only simulation was carried out on a single patient-based geometry and results from this simulation were compared with experimental results. There was good qualitative and quantitative agreement between the experimental and numerical results, suggesting that OpenFOAM is capable of predicting the main features of unsteady flow through a complex patient-based abdominal aortic aneurysm geometry. The intraluminal thrombus and arterial wall were then included, and solid stress and fluid-structure interaction simulations were performed on this, and two other patient-based abdominal aortic aneurysm geometries. It was found that the solid stress simulations resulted in an under-estimation of the maximum stress by up to 5.9% when compared with the fluid-structure interaction simulations. In the fluid-structure interaction simulations, flow induced pressure within the aneurysm was found to be up to 4.8% higher than the value of peak systolic pressure imposed in the solid stress simulations, which is likely to be the cause of the variation in the stress results. In comparing the results from the initial fluid-only simulation with results from the fluid-structure interaction simulation on the same patient, it was found that wall shear stress values varied by up to 35% between the two simulation methods. It was concluded that solid stress simulations are adequate to predict the maximum stress in an aneurysm wall, while fluid-structure interaction simulations should be performed if accurate prediction of the fluid wall shear stress is necessary. Therefore, the decision to perform fluid-structure interaction simulations should be based on the particular variables of interest in a given study.

Improvement in conformability of the latest generation of thoracic stent grafts.

PubMed

Canaud, Ludovic; Cathala, Philipe; Joyeux, Frédéric; Branchereau, Pascal; Marty-Ané, Charles; Alric, Pierre

2013-04-01

Poor aortic arch apposition increases the risk of technical failure after thoracic endovascular repair. The aim of this study was to assess the conformability of the latest generation of thoracic stent grafts in relation to the degree of device oversizing and aortic arch angulation. A benchtop pulsatile flow model was designed to test stent graft anchorage in a 2-cm-long proximal landing zone at varying landing zone angles (from 140° down to 70°) and stent graft oversizing (12%-28%). The experiments were performed using 10 human thoracic cadaveric aortas and four stent grafts: C-TAG, Zenith TX2 Pro-Form, Valiant Captivia, and Relay. Device-wall apposition was measured as a function of landing zone angulation and oversizing during static and dynamic (60 pulses/min, 300/150 mm Hg) tests. The Valiant stent graft remained apposed to the aortic wall at each increment of neck angulation and device oversizing. Lack of apposition of the proximal anchorage segment was observed with the C-TAG above 120° landing zone angulation (1-2 mm) and with the Relay above 110° landing zone angulation (1-4 mm). Lack of "body" apposition (1-4 mm) was first observed with the Zenith Pro-Form stent graft above 110° angulation (P = .001). When the device was not apposed to the aortic wall, an increase in stent graft oversizing significantly (P = .01) decreased device-wall apposition. The requirement for close conformability has influenced the design of next-generation devices. Manufacturers have modified devices and/or their deployment system to specifically address this problem. When compared with the results of our previous experimental test, this study demonstrates that these alterations have resulted in a marked improvement in the performance of commercially available stent graft systems. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Understanding the pathogenesis of abdominal aortic aneurysms

PubMed Central

Kuivaniemi, Helena; Ryer, Evan J.; Elmore, James R.; Tromp, Gerard

2016-01-01

Summary An aortic aneurysm is a dilatation in which the aortic diameter is ≥ 3.0 cm. If left untreated, the aortic wall continues to weaken and becomes unable to withstand the forces of the luminal blood pressure resulting in progressive dilatation and rupture, a catastrophic event associated with a mortality of 50 – 80%. Smoking and positive family history are important risk factors for the development of abdominal aortic aneurysms (AAA). Several genetic risk factors have also been identified. On the histological level, visible hallmarks of AAA pathogenesis include inflammation, smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. We expect that large genetic, genomic, epigenetic, proteomic and metabolomic studies will be undertaken by international consortia to identify additional risk factors and biomarkers, and to enhance our understanding of the pathobiology of AAA. Collaboration between different research groups will be important in overcoming the challenges to develop pharmacological treatments for AAA. PMID:26308600

Wall stress reduction in abdominal aortic aneurysms as a result of polymeric endoaortic paving.

PubMed

Ashton, John H; Ayyalasomayajula, Avinash; Simon, Bruce R; Vande Geest, Jonathan P

2011-06-01

Polymeric endoaortic paving (PEAP) may improve endovascular repair of abdominal aortic aneurysms (AAA) since it has the potential to treat patients with complex AAA geometries while reducing the incidence of migration and endoleak. Polycaprolactone (PCL)/polyurethane (PU) blends are proposed as PEAP materials due to their range of mechanical properties, thermoformability, and resistance to biodegradation. In this study, the reduction in AAA wall stress that can be achieved using PEAP was estimated and compared to that resulting from stent-grafts. This was accomplished by mechanically modeling the anisotropic response of PCL/PU blends and implementing these results into finite element model (FEM) simulations. We found that at the maximum diameter of the AAA, the 50/50 and 10/90 PCL/PU blends reduced wall stress by 99 and 98%, respectively, while a stent-graft reduced wall stress by 99%. Our results also show that wall stress reduction increases with increasing PEAP thickness and PCL content in the blend ratio. These results indicate that PEAP can reduce AAA wall stress as effectively as a stent-graft. As such, we propose that PEAP may provide an improved treatment alternative for AAA, since many of the limitations of stent-grafts have the potential to be solved using this approach.

Disturbed P53-MDM2 Feedback Loop Contributes to Thoracic Aortic Dissection Formation and May be a Result of TRIM25 Overexpression.

PubMed

Gong, Bin; Wang, Zhiwei; Zhang, Min; Hu, Zhipeng; Ren, Zongli; Tang, Zheng; Jiang, Wanli; Cheng, Lianghao; Huang, Jun; Ren, Wei; Wang, Qingtao

2017-04-01

The development of thoracic aortic dissection (TAD) is attributed to a broad range of degenerative, genetic, structural, oxidative, apoptotic, and acquired disease states. In this study, we examined the role of the disturbed p53-MDM2 (murine double minute 2) feedback loop in the formation of TAD, and one of a potential feedback loop regulator, TRIM25 (tripartite motif protein-25). Surgical specimens of the aorta from TAD patients (n = 10) and controls (n = 10) were tested for α-smooth muscle actin (α-SMA), p53, MDM2, and TRIM25 by western blot, immunohistochemical staining, and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), respectively. When compared with controls, western blot shows that the protein levels of p53, MDM2, and TRIM25 were increased significantly in the aortic media of TAD patients. qRT-PCR further verified that the mRNA expression of MDM2 and TRIM25 was also increased 6- and 4-folds, respectively, in the TAD media of the aortic wall. Immunohistochemistry results showed significantly decreased staining of α-SMA, smooth muscle cells, and more collagen deposition in the media of the aortic wall from patients with TAD. This study provided a new insight into the disturbed p53-MDM2 feedback loop in the pathogenesis of TAD, and this may be because of the TRIM25 overexpression. Copyright © 2016 Elsevier Inc. All rights reserved.

Ascending aortic curvature as an independent risk factor for type A dissection, and ascending aortic aneurysm formation: a mathematical model.

PubMed

Poullis, Michael P; Warwick, Richard; Oo, Aung; Poole, Robert J

2008-06-01

To develop a mathematical model to demonstrate that ascending aortic curvature is an independent risk factor for type A dissections, in addition to hypertension, bicuspid aortic valve, aneurysm of ascending aorta, and intrinsic aortic tissue abnormalities, like Marfan's syndrome. A steady state one-dimensional flow analysis was performed, utilising Newton's third law of motion. Five different clinical scenarios were evaluated: (1) effect of aortic curvature; (2) effect of beta-blockers, (3) effect of patient size, (4) forces on a Marfan's aorta, and (5) site of entry flap in aortic dissection. Aortic curvature increases the forces exerted on the ascending aorta by a factor of over 10-fold. Aortic curvature can cause patients with a systolic blood pressure of 8 0mmHg to have greater forces exerted on their aorta despite smaller diameters and lower cardiac outputs, than patients with systolic blood pressures of 120 mmHg. In normal diameter aortas, beta-blockers have minimal effect compared with aortic curvature. Aortic curvature may help to explain why normal diameter aortas can dissect, and also that the point of the entry tear may be potentially predictable. Aortic curvature has major effects on the forces exerted on the aorta in patients with Marfan's syndrome. Aortic curvature is relatively more important that aortic diameter, blood pressure, cardiac output, beta-blocker use, and patient size with regard to the force acting on the aortic wall. This may explain why some patients with normal diameter ascending aortas with or without Marfan's syndrome develop type A dissections and aneurysms. Aortic curvature may also help to explain the site of entry tear in acute type A dissection. Further clinical study is needed to validate this study's finding.

Nanoparticulate delivery of agents for induced elastogenesis in three-dimensional collagenous matrices.

PubMed

Venkataraman, Lavanya; Sivaraman, Balakrishnan; Vaidya, Pratik; Ramamurthi, Anand

2016-12-01

The degradation of elastic matrix in the infrarenal aortic wall is a critical parameter underlying the formation and progression of abdominal aortic aneurysms. It is mediated by the chronic overexpression of matrix metalloprotease (MMP)-2 and MMP-9, leading to a progressive loss of elasticity and weakening of the aortic wall. Delivery of therapeutic agents to inhibit MMPs, while concurrently coaxing cell-based regenerative repair of the elastic matrix represents a potential strategy for slowing or arresting abdominal aortic aneurysm growth. Previous studies have demonstrated elastogenic induction of healthy and aneurysmal aortic smooth muscle cells and inhibition of MMPs, following exogenous delivery of elastogenic factors such as transforming growth factor (TGF)-β1, as well as MMP-inhibitors such as doxycycline (DOX) in two-dimensional culture. Based on these findings, and others that demonstrated elastogenic benefits of nanoparticulate delivery of these agents in two-dimensional culture, poly(lactide-co-glycolide) nanoparticles were developed for localized, controlled and sustained delivery of DOX and TGF-β1 to human aortic smooth muscle cells within a three-dimensional gels of type I collagen, which closely simulate the arterial tissue microenvironment. DOX and TGF-β1 released from these nanoparticles influenced elastogenic outcomes positively within the collagen constructs over 21 days of culture, which were comparable to that induced by exogenous supplementation of DOX and TGF-β1 within the culture medium. However, this was accomplished at doses ~20-fold lower than the exogenous dosages of the agents, illustrating that their localized, controlled and sustained delivery from nanoparticles embedded within a three-dimensional scaffold is an efficient strategy for directed elastogenesis. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

A Methodology to Detect Abnormal Relative Wall Shear Stress on the Full Surface of the Thoracic Aorta Using 4D Flow MRI

PubMed Central

van Ooij, Pim; Potters, Wouter V.; Nederveen, Aart J.; Allen, Bradley D.; Collins, Jeremy; Carr, James; Malaisrie, S. Chris; Markl, Michael; Barker, Alex J.

2014-01-01

Purpose To compute cohort-averaged wall shear stress (WSS) maps in the thoracic aorta of patients with aortic dilatation or valvular stenosis and to detect abnormal regional WSS. Methods Systolic WSS vectors, estimated from 4D flow MRI data, were calculated along the thoracic aorta lumen in 10 controls, 10 patients with dilated aortas and 10 patients with aortic valve stenosis. 3D segmentations of each aorta were co-registered by group and used to create a cohort-specific aortic geometry. The WSS vectors of each subject were interpolated onto the corresponding cohort-specific geometry to create cohort-averaged WSS maps. A Wilcoxon rank sum test was used to generate aortic P-value maps (P<0.05) representing regional relative WSS differences between groups. Results Cohort-averaged systolic WSS maps and P-value maps were successfully created for all cohorts and comparisons. The dilation cohort showed significantly lower WSS on 7% of the ascending aorta surface, whereas the stenosis cohort showed significantly higher WSS aorta on 34% the ascending aorta surface. Conclusions The findings of this study demonstrated the feasibility of generating cohort-averaged WSS maps for the visualization and identification of regionally altered WSS in the presence of disease, as compared to healthy controls. PMID:24753241

Hemodynamics in an Aorta with Bicuspid and Trileaflet Valves

NASA Astrophysics Data System (ADS)

Gilmanov, Anvar; Sotiropoulos, Fotis

2015-11-01

Bicuspid aortic valve (BAV) is a congenital heart defect that has been associated with serious aortopathies, such as ascending aortic aneurysm, aortic stenosis, aortic regurgitation, infective endocarditis, aortic dissection, calcific aortic valve and dilatation of ascending aorta. Two main hypotheses - the genetic and the hemodynamic are discussed in literature to explain the development and progression of aortopathies in patients with BAV. In this study we seek to investigate the possible role of hemodynamic factors as causes of BAV-associated aortopathy. We employ the Curvilinear Immersed Boundary (CURVIB) method coupled with an efficient thin-shell finite element (TS-FE) formulation for tissues to carry out fluid-structure interaction simulations of a healthy tri-leaflet aortic valve (TAV) and a BAV placed in the same anatomic aorta. The computed results reveal major differences between the TAV and BAV flow patterns. These include: the dynamics of the aortic valve vortex ring formation and break up; the large scale flow patterns in the ascending aorta; and the shear stress magnitude on the aortic wall. The computed results are in qualitative agreement with in vivo Magnetic Resonance Imaging (MRI) data and suggest that the linkages between BAV aortopathy and hemodynamics deserve further investigation. This work is supported by the Lillehei Heart Institute at the University of Minnesota and the Minnesota Supercomputing Institute.

Enhancing 4D PC-MRI in an aortic phantom considering numerical simulations

NASA Astrophysics Data System (ADS)

Kratzke, Jonas; Schoch, Nicolai; Weis, Christian; Müller-Eschner, Matthias; Speidel, Stefanie; Farag, Mina; Beller, Carsten J.; Heuveline, Vincent

2015-03-01

To date, cardiovascular surgery enables the treatment of a wide range of aortic pathologies. One of the current challenges in this field is given by the detection of high-risk patients for adverse aortic events, who should be treated electively. Reliable diagnostic parameters, which indicate the urge of treatment, have to be determined. Functional imaging by means of 4D phase contrast-magnetic resonance imaging (PC-MRI) enables the time-resolved measurement of blood flow velocity in 3D. Applied to aortic phantoms, three dimensional blood flow properties and their relation to adverse dynamics can be investigated in vitro. Emerging "in silico" methods of numerical simulation can supplement these measurements in computing additional information on crucial parameters. We propose a framework that complements 4D PC-MRI imaging by means of numerical simulation based on the Finite Element Method (FEM). The framework is developed on the basis of a prototypic aortic phantom and validated by 4D PC-MRI measurements of the phantom. Based on physical principles of biomechanics, the derived simulation depicts aortic blood flow properties and characteristics. The framework might help identifying factors that induce aortic pathologies such as aortic dilatation or aortic dissection. Alarming thresholds of parameters such as wall shear stress distribution can be evaluated. The combined techniques of 4D PC-MRI and numerical simulation can be used as complementary tools for risk-stratification of aortic pathology.

Endovascular treatment of traumatic thoracic aortic injuries: short- and medium-term Follow-up.

PubMed

Fernandez, Valentín; Mestres, Gaspar; Maeso, Jordi; Domínguez, José Manuel; Aloy, M Carmen; Matas, Manel

2010-02-01

Successful thoracic endovascular aortic repair (TEVAR) with low rates of complications has been referred to in the treatment of traumatic thoracic aortic injuries; however, we still do not know the long-term behavior. In this series, short- and intermediate-term results of TEVAR of traumatic aortic injuries are analyzed. The clinical charts and courses of 20 patients (mean age, 31.8 years; age range, 15-65 years; 14 [70%] men) with traumatic thoracic aortic injuries treated with TEVAR were retrospectively reviewed. Mean delay from trauma to intervention was 15 days (range, 0-180 days). The initial success rate was 100%, with no deaths or intraoperative leaks, although in 4 (20%) patients, injuries were repaired in the arterial access site. The mean postoperative follow-up was 43.53 months (range, 5.5-108.0 months). Four (20%) patients required reintervention: 2 postoperative revascularizations of the left subclavian artery (20% of the patients in whom the ostium was intentionally occluded) and 2 aortic reinterventions (endovascular treatment of a collapsed stent graft and open repair after thrombosis of another stent graft). All reinterventions were successfully performed and no additional complications were registered during follow-up. Asymptomatic findings related to the stent graft included lack of proximal device-wall apposition in 8 patients (40%), intragraft mural thrombus formation during the first 6 months in 7 patients (35%), and an asymptomatic fracture of the longitudinal reinforcing bar of the stent graft 4 years later in 1 patient (5%). Although not completely exempt of complications, TEVAR provides a reliable method for the treatment of traumatic thoracic aortic injuries with good results in the short- and medium-term follow-up. All complications have been treated successfully. Long-term evolution of lack of proximal device-wall apposition and intragraft mural thrombus formation should be closely monitored to prevent long-term complications. Copyright 2006 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

Adventitial adipogenic degeneration is an unidentified contributor to aortic wall weakening in the abdominal aortic aneurysm.

PubMed

Doderer, Stefan A; Gäbel, Gabor; Kokje, Vivianne B C; Northoff, Bernd H; Holdt, Lesca M; Hamming, Jaap F; Lindeman, Jan H N

2018-06-01

The processes driving human abdominal aortic aneurysm (AAA) progression are not fully understood. Although antiinflammatory and proteolytic strategies effectively quench aneurysm progression in preclinical models, so far all clinical interventions failed. These observations hint at an incomplete understanding of the processes involved in AAA progression and rupture. Interestingly, strong clinical and molecular associations exist between popliteal artery aneurysms (PAAs) and AAAs; however, PAAs have an extremely low propensity to rupture. We thus reasoned that differences between these aneurysms may provide clues toward (auxiliary) processes involved in AAA-related wall debilitation. A better understanding of the pathophysiologic processes driving AAA growth can contribute to pharmaceutical treatments in the future. Aneurysmal wall samples were collected during open elective and emergency repair. Control perirenal aorta was obtained during kidney transplantation, and reference popliteal tissue obtained from the anatomy department. This study incorporates various techniques including (immuno)histochemistry, Western Blot, quantitative polymerase chain reaction, microarray, and cell culture. Histologic evaluation of AAAs, PAAs, and control aorta shows extensive medial (PAA) and transmural fibrosis (AAA), and reveals abundant adventitial adipocytes aggregates as an exclusive phenomenon of AAAs (P < .001). Quantitative polymerase chain reaction, immunohistochemistry, Western blotting, and microarray analysis showed enrichment of adipogenic mediators (C/EBP family P = .027; KLF5 P < .000; and peroxisome proliferator activated receptor-γ, P = .032) in AAA tissue. In vitro differentiation tests indicated a sharply increased adipogenic potential of AAA adventitial mesenchymal cells (P < .0001). Observed enrichment of adipocyte-related genes and pathways in ruptured AAA (P < .0003) supports an association between the extent of fatty degeneration and rupture. This translational study identifies extensive adventitial fatty degeneration as an ignored and distinctive feature of AAA disease. Enrichment of adipocyte genesis and adipocyte-related genes in ruptured AAA point to an association between the extent of fatty degeneration and rupture. This observation may (partly) explain the failure of medical therapy and could provide a lead for pharmaceutical alleviation of AAA progression. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Enhanced caspase activity contributes to aortic wall remodeling and early aneurysm development in a murine model of Marfan syndrome.

PubMed

Emrich, Fabian C; Okamura, Homare; Dalal, Alex R; Penov, Kiril; Merk, Denis R; Raaz, Uwe; Hennigs, Jan K; Chin, Jocelyn T; Miller, Miquell O; Pedroza, Albert J; Craig, Juliana K; Koyano, Tiffany K; Blankenberg, Francis G; Connolly, Andrew J; Mohr, Friedrich W; Alvira, Cristina M; Rabinovitch, Marlene; Fischbein, Michael P

2015-01-01

Rupture and dissection of aortic root aneurysms remain the leading causes of death in patients with the Marfan syndrome, a hereditary connective tissue disorder that affects 1 in 5000 individuals worldwide. In the present study, we use a Marfan mouse model (Fbn1(C1039G/+)) to investigate the biological importance of apoptosis during aneurysm development in Marfan syndrome. Using in vivo single-photon emission computed tomographic-imaging and ex vivo autoradiography for Tc99m-annexin, we discovered increased apoptosis in the Fbn1(C1039G/+) ascending aorta during early aneurysm development peaking at 4 weeks. Immunofluorescence colocalization studies identified smooth muscle cells (SMCs) as the apoptotic cell population. As biological proof of concept that early aortic wall apoptosis plays a role in aneurysm development in Marfan syndrome, Fbn1(C1039G/+) mice were treated daily from 2 to 6 weeks with either (1) a pan-caspase inhibitor, Q-VD-OPh (20 mg/kg), or (2) vehicle control intraperitoneally. Q-VD-OPh treatment led to a significant reduction in aneurysm size and decreased extracellular matrix degradation in the aortic wall compared with control mice. In vitro studies using Fbn1(C1039G/+) ascending SMCs showed that apoptotic SMCs have increased elastolytic potential compared with viable cells, mostly because of caspase activity. Moreover, in vitro (1) cell membrane isolation, (2) immunofluorescence staining, and (3) scanning electron microscopy studies illustrate that caspases are expressed on the exterior cell surface of apoptotic SMCs. Caspase inhibition attenuates aneurysm development in an Fbn1(C1039G/+) Marfan mouse model. Mechanistically, during apoptosis, caspases are expressed on the cell surface of SMCs and likely contribute to elastin degradation and aneurysm development in Marfan syndrome. © 2014 American Heart Association, Inc.

The influence of the aortic valve angle on the hemodynamic features of the thoracic aorta

NASA Astrophysics Data System (ADS)

Ha, Hojin; Kim, Guk Bae; Kweon, Jihoon; Lee, Sang Joon; Kim, Young-Hak; Kim, Namkug; Yang, Dong Hyun

2016-08-01

Since the first observation of a helical flow pattern in aortic blood flow, the existence of helical blood flow has been found to be associated with various pathological conditions such as bicuspid aortic valve, aortic stenosis, and aortic dilatation. However, an understanding of the development of helical blood flow and its clinical implications are still lacking. In our present study, we hypothesized that the direction and angle of aortic inflow can influence helical flow patterns and related hemodynamic features in the thoracic aorta. Therefore, we investigated the hemodynamic features in the thoracic aorta and various aortic inflow angles using patient-specific vascular phantoms that were generated using a 3D printer and time-resolved, 3D, phase-contrast magnetic resonance imaging (PC-MRI). The results show that the rotational direction and strength of helical blood flow in the thoracic aorta largely vary according to the inflow direction of the aorta, and a higher helical velocity results in higher wall shear stress distributions. In addition, right-handed rotational flow conditions with higher rotational velocities imply a larger total kinetic energy than left-handed rotational flow conditions with lower rotational velocities.

The influence of the aortic valve angle on the hemodynamic features of the thoracic aorta.

PubMed

Ha, Hojin; Kim, Guk Bae; Kweon, Jihoon; Lee, Sang Joon; Kim, Young-Hak; Kim, Namkug; Yang, Dong Hyun

2016-08-26

Since the first observation of a helical flow pattern in aortic blood flow, the existence of helical blood flow has been found to be associated with various pathological conditions such as bicuspid aortic valve, aortic stenosis, and aortic dilatation. However, an understanding of the development of helical blood flow and its clinical implications are still lacking. In our present study, we hypothesized that the direction and angle of aortic inflow can influence helical flow patterns and related hemodynamic features in the thoracic aorta. Therefore, we investigated the hemodynamic features in the thoracic aorta and various aortic inflow angles using patient-specific vascular phantoms that were generated using a 3D printer and time-resolved, 3D, phase-contrast magnetic resonance imaging (PC-MRI). The results show that the rotational direction and strength of helical blood flow in the thoracic aorta largely vary according to the inflow direction of the aorta, and a higher helical velocity results in higher wall shear stress distributions. In addition, right-handed rotational flow conditions with higher rotational velocities imply a larger total kinetic energy than left-handed rotational flow conditions with lower rotational velocities.

Aortic Wave Dynamics and Its Influence on Left Ventricular Workload

NASA Astrophysics Data System (ADS)

Pahlevan, Niema; Gharib, Morteza

2010-11-01

Clinical and epidemiologic studies have shown that hypertension plays a key role in development of left ventricular (LV) hypertrophy and ultimately heart failure mostly due to increased LV workload. Therefore, it is crucial to diagnose and treat abnormal high LV workload at early stages. The pumping mechanism of the heart is pulsatile, thus it sends pressure and flow wave into the compliant aorta. The wave dynamics in the aorta is dominated by interplay of heart rate (HR), aortic rigidity, and location of reflection sites. We hypothesized that for a fixed cardiac output (CO) and peripheral resistance (PR), interplay of HR and aortic compliance can create conditions that minimize LV power requirement. We used a computational approach to test our hypothesis. Finite element method with direct coupling method of fluid-structure interaction (FSI) was used. Blood was assumed to be incompressible Newtonian fluid and aortic wall was considered elastic isotropic. Simulations were performed for various heart rates and aortic rigidities while inflow wave, CO, and PR were kept constant. For any aortic compliance, LV power requirement becomes minimal at a specific heart rate. The minimum shifts to higher heart rates as aortic rigidity increases.

The influence of the aortic valve angle on the hemodynamic features of the thoracic aorta

PubMed Central

Ha, Hojin; Kim, Guk Bae; Kweon, Jihoon; Lee, Sang Joon; Kim, Young-Hak; Kim, Namkug; Yang, Dong Hyun

2016-01-01

Since the first observation of a helical flow pattern in aortic blood flow, the existence of helical blood flow has been found to be associated with various pathological conditions such as bicuspid aortic valve, aortic stenosis, and aortic dilatation. However, an understanding of the development of helical blood flow and its clinical implications are still lacking. In our present study, we hypothesized that the direction and angle of aortic inflow can influence helical flow patterns and related hemodynamic features in the thoracic aorta. Therefore, we investigated the hemodynamic features in the thoracic aorta and various aortic inflow angles using patient-specific vascular phantoms that were generated using a 3D printer and time-resolved, 3D, phase-contrast magnetic resonance imaging (PC-MRI). The results show that the rotational direction and strength of helical blood flow in the thoracic aorta largely vary according to the inflow direction of the aorta, and a higher helical velocity results in higher wall shear stress distributions. In addition, right-handed rotational flow conditions with higher rotational velocities imply a larger total kinetic energy than left-handed rotational flow conditions with lower rotational velocities. PMID:27561388

Ultrasonic delineation of aortic microstructure: The relative contribution of elastin and collagen to aortic elasticity

NASA Astrophysics Data System (ADS)

Marsh, Jon N.; Takiuchi, Shin; Lin, Shiow Jiuan; Lanza, Gregory M.; Wickline, Samuel A.

2004-05-01

Aortic elasticity is an important factor in hemodynamic health, and compromised aortic compliance affects not only arterial dynamics but also myocardial function. A variety of pathologic processes (e.g., diabetes, Marfan's syndrome, hypertension) can affect aortic elasticity by altering the microstructure and composition of the elastin and collagen fiber networks within the tunica media. Ultrasound tissue characterization techniques can be used to obtain direct measurements of the stiffness coefficients of aorta by measurement of the speed of sound in specific directions. In this study we sought to define the contributions of elastin and collagen to the mechanical properties of aortic media by measuring the magnitude and directional dependence of the speed of sound before and after selective isolation of either the collagen or elastin fiber matrix. Formalin-fixed porcine aortas were sectioned for insonification in the circumferential, longitudinal, or radial direction and examined using high-frequency (50 MHz) ultrasound microscopy. Isolation of the collagen or elastin fiber matrices was accomplished through treatment with NaOH or formic acid, respectively. The results suggest that elastin is the primary contributor to aortic medial stiffness in the unloaded state, and that there is relatively little anisotropy in the speed of sound or stiffness in the aortic wall.

Particle Image Velocimetry studies of bicuspid aortic valve hemodynamics

NASA Astrophysics Data System (ADS)

Saikrishnan, Neelakantan; Yap, Choon-Hwai; Yoganathan, Ajit P.

2010-11-01

Bicuspid aortic valves (BAVs) are a congenital anomaly of the aortic valve with two fused leaflets, affecting about 1-2% of the population. BAV patients have much higher incidence of valve calcification & aortic dilatation, which may be related to altered mechanical forces from BAV hemodynamics. This study aims to characterize BAV hemodynamics using Particle Image Velocimetry(PIV). BAV models are constructed from normal explanted porcine aortic valves by suturing two leaflets together. The valves are mounted in an acrylic chamber with two sinuses & tested in a pulsatile flow loop at physiological conditions. 2D PIV is performed to obtain flow fields in three planes downstream of the valve. The stenosed BAV causes an eccentric jet, resulting in a very strong vortex in the normal sinus. The bicuspid sinus vortex appears much weaker, but more unstable. Unsteady oscillatory shear stresses are also observed, which have been associated with adverse biological response; characterization of the hemodynamics of BAVs will provide the first step to understanding these processes better. Results from multiple BAV models of varying levels of stenosis will be presented & higher stenosis corresponded to stronger jets & increased aortic wall shear stresses.

Blood flow dynamic improvement with aneurysm repair detected by a patient-specific model of multiple aortic aneurysms.

PubMed

Sughimoto, Koichi; Takahara, Yoshiharu; Mogi, Kenji; Yamazaki, Kenji; Tsubota, Ken'ichi; Liang, Fuyou; Liu, Hao

2014-05-01

Aortic aneurysms may cause the turbulence of blood flow and result in the energy loss of the blood flow, while grafting of the dilated aorta may ameliorate these hemodynamic disturbances, contributing to the alleviation of the energy efficiency of blood flow delivery. However, evaluating of the energy efficiency of blood flow in an aortic aneurysm has been technically difficult to estimate and not comprehensively understood yet. We devised a multiscale computational biomechanical model, introducing novel flow indices, to investigate a single male patient with multiple aortic aneurysms. Preoperative levels of wall shear stress and oscillatory shear index (OSI) were elevated but declined after staged grafting procedures: OSI decreased from 0.280 to 0.257 (first operation) and 0.221 (second operation). Graftings may strategically counter the loss of efficient blood delivery to improve hemodynamics of the aorta. The energy efficiency of blood flow also improved postoperatively. Novel indices of pulsatile pressure index (PPI) and pulsatile energy loss index (PELI) were evaluated to characterize and quantify energy loss of pulsatile blood flow. Mean PPI decreased from 0.445 to 0.423 (first operation) and 0.359 (second operation), respectively; while the preoperative PELI of 0.986 dropped to 0.820 and 0.831. Graftings contributed not only to ameliorate wall shear stress or oscillatory shear index but also to improve efficient blood flow. This patient-specific modeling will help in analyzing the mechanism of aortic aneurysm formation and may play an important role in quantifying the energy efficiency or loss in blood delivery.

Induction of Macrophage Chemotaxis by Aortic Extracts from Patients with Marfan Syndrome Is Related to Elastin Binding Protein

PubMed Central

Guo, Gao; Gehle, Petra; Doelken, Sandra; Martin-Ventura, José Luis; von Kodolitsch, Yskert; Hetzer, Roland; Robinson, Peter N.

2011-01-01

Marfan syndrome is an autosomal dominantly inherited disorder of connective tissue with prominent skeletal, ocular, and cardiovascular manifestations. Aortic aneurysm and dissection are the major determinants of premature death in untreated patients. In previous work, we showed that extracts of aortic tissues from the mgR mouse model of Marfan syndrome showed increased chemotactic stimulatory activity related to the elastin-binding protein. Aortic samples were collected from 6 patients with Marfan syndrome and 8 with isolated aneurysms of the ascending aorta. Control samples were obtained from 11 organ donors without known vascular or connective tissue diseases. Soluble proteins extracted from the aortic samples of the two patient groups were compared against buffer controls and against the aortic samples from controls with respect to the ability to induce macrophage chemotaxis as measured using a modified Boyden chamber, as well as the reactivity to a monoclonal antibody BA4 against bioactive elastin peptides using ELISA. Samples from Marfan patients displayed a statistically significant increase in chemotactic inductive activity compared to control samples. Additionally, reactivity to BA4 was significantly increased. Similar statistically significant increases were identified for the samples from patients with idiopathic thoracic aortic aneurysm. There was a significant correlation between the chemotactic index and BA4 reactivity, and the increases in chemotactic activity of extracts from Marfan patients could be inhibited by pretreatment with lactose, VGVAPG peptides, or BA4, which indicates the involvement of EBP in mediating the effects. Our results demonstrate that aortic extracts of patients with Marfan syndrome can elicit macrophage chemotaxis, similar to our previous study on aortic extracts of the mgR mouse model of Marfan syndrome (Guo et al., Circulation 2006; 114:1855-62). PMID:21647416

A pull-back algorithm to determine the unloaded vascular geometry in anisotropic hyperelastic AAA passive mechanics.

PubMed

Riveros, Fabián; Chandra, Santanu; Finol, Ender A; Gasser, T Christian; Rodriguez, Jose F

2013-04-01

Biomechanical studies on abdominal aortic aneurysms (AAA) seek to provide for better decision criteria to undergo surgical intervention for AAA repair. More accurate results can be obtained by using appropriate material models for the tissues along with accurate geometric models and more realistic boundary conditions for the lesion. However, patient-specific AAA models are generated from gated medical images in which the artery is under pressure. Therefore, identification of the AAA zero pressure geometry would allow for a more realistic estimate of the aneurysmal wall mechanics. This study proposes a novel iterative algorithm to find the zero pressure geometry of patient-specific AAA models. The methodology allows considering the anisotropic hyperelastic behavior of the aortic wall, its thickness and accounts for the presence of the intraluminal thrombus. Results on 12 patient-specific AAA geometric models indicate that the procedure is computational tractable and efficient, and preserves the global volume of the model. In addition, a comparison of the peak wall stress computed with the zero pressure and CT-based geometries during systole indicates that computations using CT-based geometric models underestimate the peak wall stress by 59 ± 64 and 47 ± 64 kPa for the isotropic and anisotropic material models of the arterial wall, respectively.

Aortic Wall Inflammation Predicts Abdominal Aortic Aneurysm Expansion, Rupture, and Need for Surgical Repair.

PubMed

2017-08-29

Ultrasmall superparamagnetic particles of iron oxide (USPIO) detect cellular inflammation on magnetic resonance imaging (MRI). In patients with abdominal aortic aneurysm, we assessed whether USPIO-enhanced MRI can predict aneurysm growth rates and clinical outcomes. In a prospective multicenter open-label cohort study, 342 patients with abdominal aortic aneurysm (diameter ≥40 mm) were classified by the presence of USPIO enhancement and were monitored with serial ultrasound and clinical follow-up for ≥2 years. The primary end point was the composite of aneurysm rupture or repair. Participants (85% male, 73.1±7.2 years) had a baseline aneurysm diameter of 49.6±7.7 mm, and USPIO enhancement was identified in 146 (42.7%) participants, absent in 191 (55.8%), and indeterminant in 5 (1.5%). During follow-up (1005±280 days), 17 (5.0%) abdominal aortic aneurysm ruptures, 126 (36.8%) abdominal aortic aneurysm repairs, and 48 (14.0%) deaths occurred. Compared with those without uptake, patients with USPIO enhancement have increased rates of aneurysm expansion (3.1±2.5 versus 2.5±2.4 mm/year, P =0.0424), although this was not independent of current smoking habit ( P =0.1993). Patients with USPIO enhancement had higher rates of aneurysm rupture or repair (47.3% versus 35.6%; 95% confidence intervals, 1.1-22.2; P =0.0308). This finding was similar for each component of rupture (6.8% versus 3.7%, P =0.1857) or repair (41.8% versus 32.5%, P =0.0782). USPIO enhancement was associated with reduced event-free survival for aneurysm rupture or repair ( P =0.0275), all-cause mortality ( P =0.0635), and aneurysm-related mortality ( P =0.0590). Baseline abdominal aortic aneurysm diameter ( P <0.0001) and current smoking habit ( P =0.0446) also predicted the primary outcome, and the addition of USPIO enhancement to the multivariate model did not improve event prediction (c-statistic, 0.7935-0.7936). USPIO-enhanced MRI is a novel approach to the identification of aortic wall cellular inflammation in patients with abdominal aortic aneurysms and predicts the rate of aneurysm growth and clinical outcome. However, it does not provide independent prediction of aneurysm expansion or clinical outcomes in a model incorporating known clinical risk factors. URL: http://www.isrctn.com. Unique identifier: ISRCTN76413758. © 2017 The Authors.

Descending aortic injury by a thoracic pedicle screw during posterior reconstructive surgery: a case report.

PubMed

Watanabe, Kei; Yamazaki, Akiyoshi; Hirano, Toru; Izumi, Tomohiro; Sano, Atsuki; Morita, Osamu; Kikuchi, Ren; Ito, Takui

2010-09-15

Case report. To describe an iatrogenic aortic injury by pedicle screw instrumentation during posterior reconstructive surgery of spinal deformity. Iatrogenic major vascular injuries during anterior instrumentation procedures have been reported by several authors, but there have been few reports regarding iatrogenic major vascular injuries during posterior instrumentation procedures. A 57-year-old woman with thoracolumbar kyphosis due to osteoporotic T12 vertebral fracture underwent posterior correction and fusion (T10-L2), using segmental pedicle screw construct concomitant with T12 pedicle subtraction osteotomy. Postoperative routine plain radiographs and computed tomography myelography demonstrated a misplaced left T10 pedicle screw, which was in contact with the posteromedial aspect of the thoracic aorta, and suspected penetration of the aortic wall. The patient underwent removal of the pedicle screw, and repair of the penetrated aortic wall through a simultaneous anterior-posterior approach. The patient tolerated the procedure well without neurologic sequelae, and was discharged several days after removal of a left tube thoracostomy. Plain radiographs demonstrated solid fusion at the osteotomy site and no loosening of hardware. Preoperative neurologic symptoms improved completely at 18-months follow-up. Use of pedicle screw instrumentation has the potential to cause major vascular injury during posterior spinal surgery, and measures to prevent this complication must be taken. Timely diagnosis and treatment are essential to prevent both early and delayed complications and death.

Catching a floating thrombus; a case report on the treatment of a large thrombus in the ascending aorta.

PubMed

de Maat, Gijs Eduard; Vigano, Giorgio; Mariani, Massimo Alessandro; Natour, Ehsan

2017-05-19

The ascending aorta is an uncommon site for non-infective thrombus. In non-aneurysmal and non-atherosclerotic vessels this condition becomes extremely rare, while it represents a source of potential cerebral and peripheral embolic events. Currently, there is no consensus in the guidelines on how to treat a free floating thrombus in ascending aorta, therefore we present our decision making process and therapeutic strategy. A healthy 48-year-old man was hospital admitted with acute abdominal pain. CT-scan showed a right renal embolism in presence of a defect in the distal ascending aorta suggestive for thrombus. After heart team discussion the patient was scheduled for surgery and successfully underwent an emergent thrombus removal. Also, owing to multiple aortic wall insertions, the ascending aorta was replaced. The patient's recovery was uneventful and histological examination showed no signs of connective tissue disorders of aortic wall while confirmed the thrombotic nature of the mass. We present a patient with a floating thrombus in the ascending aorta who underwent an ascending aorta replacement. While angio-CT scan led to a prompt diagnosis, intraoperative epi-aortic echocardiography allowed to define precise location of thrombus, minimizing operative risk. This case demonstrates that multi-disciplinary heart team discussion is essential to define a successful strategy, that surgical treatment is feasible with specific tools such as epi-aortic echocardiography.

Acute myocardial infarction due to spontaneous, localized, acute dissection of the sinus of Valsalva detected by intravascular ultrasound and electrocardiogram-gated computed tomography.

PubMed

Ichihashi, Taku; Ito, Tsuyoshi; Murai, Shunsuke; Ikehara, Noriyuki; Fujita, Hiroshi; Suda, Hisao; Ohte, Nobuyuki

2016-09-01

A 58-year-old man was referred to our hospital because of chest pain. The 12-lead electrocardiogram (ECG) revealed ST-segment elevation in II, III, and a Vf with advanced heart block. Transthoracic echocardiography demonstrated aortic root dilatation at the sinus of Valsalva, moderate aortic regurgitation, and decreased wall motion in the inferior part of the left ventricle. Non-ECG-gated enhanced computed tomography (CT) did not reveal an aortic dissection. The patient underwent emergent coronary angiography, which revealed a severely narrowed ostium of the right coronary artery (RCA). Percutaneous coronary intervention (PCI) was performed under intravascular ultrasound (IVUS) guidance. IVUS images demonstrated an intimal flap extending from the aortic wall to the proximal RCA, suggesting that a periaortic hematoma in the false lumen compressed the ostium of the RCA, leading to acute myocardial infarction. To recover hemodynamic stability, the RCA ostium was stented. Subsequent ECG-gated enhanced CT clearly depicted the entry point and extension of the dissection localized within the sinus of Valsalva. The dissection likely involved the left main coronary artery and an emergent Bentall procedure was performed. Intraoperative findings confirmed an intimal tear and extension of the dissection. Thus, ECG-gated CT can clearly depict the entry site and extension of a dissection occurring in the localized area that cannot be detected by conventional CT.

Detection of atheroma using Photofrin IIr and laser-induced fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Vari, Sandor G.; Papazoglou, Theodore G.; van der Veen, Maurits J.; Papaioannou, Thanassis; Fishbein, Michael C.; Chandra, Mudjianto; Beeder, Clain; Shi, Wei-Qiang; Grundfest, Warren S.

1991-06-01

The goal of this study was to investigate laser induced fluorescence spectroscopy (LIFS) as a method of localization of atherosclerotic lesions not visible by angiography using Photofrin IIr enhanced fluorescence. Twenty-four New Zealand White rabbits divided into six groups varying in type of arterial wall lesion and Photofrin IIr administration time (i.v.) were used. Aortic wall fluorescence signals were acquired from the aortic arch to iliac bifurcation. The output of a He-Cd laser (442 nm, 17 mW) was directed at the arterial wall through a 400 micron fiber. The fluorescence signal created in the arterial wall was collected via the same fiber and analyzed by an optical multi-channel analyzer (OMA). The ratio of fluorescence intensities at 630 nm (Photofrin IIr) and 540 nm (autofluorescence of artery wall) was analyzed (I630nm/I540nm). Intensity ratio values 24 hours after administration of Photofrin IIr were found to be as follows: in normal artery wall of 0.30 +/- 0.14 (n equals 3), in mechanically damaged wall of 0.91 +/- 0.65 (n equals 2) and, in atheromatous tissue, 0.88 +/- 0.54 (n equals 4). The intensity ratio of atheromatous tissue without Photofrin IIr was 0.23 +/- 0.04 (n equals 7). These results suggest that the use of Photofrin IIr allows in vivo atheroma detection by LIFS because of its ability to accumulate in atheroma. In addition, accumulation of Photofrin IIr was found in artery walls traumatized by balloon catheter intervention. Using this method, a catheter-based LIFS system may be developed for atheroma detection.

Adventitial Tertiary Lymphoid Organs as Potential Source of MicroRNA Biomarkers for Abdominal Aortic Aneurysm

PubMed Central

Spear, Rafaelle; Boytard, Ludovic; Blervaque, Renaud; Chwastyniak, Maggy; Hot, David; Vanhoutte, Jonathan; Staels, Bart; Lemoine, Yves; Lamblin, Nicolas; Pruvot, François-René; Haulon, Stephan; Amouyel, Philippe; Pinet, Florence

2015-01-01

Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with marked changes in the cellular composition of the aortic wall. This study aims to identify microRNA (miRNA) expression in aneurysmal inflammatory cells isolated by laser microdissection from human tissue samples. The distribution of inflammatory cells (neutrophils, B and T lymphocytes, mast cells) was evaluated in human AAA biopsies. We observed in half of the samples that adventitial tertiary lymphoid organs (ATLOs) with a thickness from 0.5 to 2 mm were located exclusively in the adventitia. Out of the 850 miRNA that were screened by microarray in isolated ATLOs (n = 2), 164 miRNAs were detected in ATLOs. The three miRNAs (miR-15a-3p, miR-30a-5p and miR-489-3p) with the highest expression levels were chosen and their expression quantified by RT-PCR in isolated ATLOs (n = 4), M1 (n = 2) and M2 macrophages (n = 2) and entire aneurysmal biopsies (n = 3). Except for the miR-30a-5p, a similar modulation was found in ATLOs and the two subtypes of macrophages. The modulated miRNAs were then evaluated in the plasma of AAA patients for their potential as AAA biomarkers. Our data emphasize the potential of miR-15a-3p and miR-30a-5p as biomarkers of AAA but also as triggers of ATLO evolution. Further investigations will be required to evaluate their targets in order to better understand AAA pathophysiology. PMID:25993295

Computational predictions of damage propagation preceding dissection of ascending thoracic aortic aneurysms.

PubMed

Mousavi, S Jamaleddin; Farzaneh, Solmaz; Avril, Stéphane

2018-04-01

Dissections of ascending thoracic aortic aneurysms (ATAAs) cause significant morbidity and mortality worldwide. They occur when a tear in the intima-media of the aorta permits the penetration of the blood and the subsequent delamination and separation of the wall in 2 layers, forming a false channel. To predict computationally the risk of tear formation, stress analyses should be performed layer-specifically and they should consider internal or residual stresses that exist in the tissue. In the present paper, we propose a novel layer-specific damage model based on the constrained mixture theory, which intrinsically takes into account these internal stresses and can predict appropriately the tear formation. The model is implemented in finite-element commercial software Abaqus coupled with user material subroutine. Its capability is tested by applying it to the simulation of different exemplary situations, going from in vitro bulge inflation experiments on aortic samples to in vivo overpressurizing of patient-specific ATAAs. The simulations reveal that damage correctly starts from the intimal layer (luminal side) and propagates across the media as a tear but never hits the adventitia. This scenario is typically the first stage of development of an acute dissection, which is predicted for pressures of about 2.5 times the diastolic pressure by the model after calibrating the parameters against experimental data performed on collected ATAA samples. Further validations on a larger cohort of patients should hopefully confirm the potential of the model in predicting patient-specific damage evolution and possible risk of dissection during aneurysm growth for clinical applications. Copyright © 2017 John Wiley & Sons, Ltd.

The risk of stanford type-A aortic dissection with different tear size and location: a numerical study.

PubMed

Shi, Yue; Zhu, Minjia; Chang, Yu; Qiao, Huanyu; Liu, Yongmin

2016-12-28

This study is to investigate the influence of hemodynamics on Stanford type-A aortic dissection with different tear size and location, to provide some support for the relationships between the risks (rupture, reverse tearing and further tearing) and tear size and location for clinical treatment. Four numerical models of Stanford type-A aortic dissection were established, with different size and location of the tears. The ratio of the area between the entry and re-entry tears(RA) is various within the model; while, the size and the location of the re-entry in the distal descending aorta are fixed. In model A11 and A21, the entry tears are located near the ascending aorta. The RA in these models are 1 and 2, respectively; In the model B11 and B21, the entry tears are located near the proximal descending aorta and the RA in these models are again assigned to 1 and 2, respectively. Then hemodynamics in these models was solved with numerically and the flow patterns and loading distributions were investigated. The flow velocity of the true lumen in model A21, B21 is lower than that in A11, B11, respectively; the time-averaged wall shear stress (TAWSS) of the false lumen in model A21 and B21 is higher, and for ascending aorta false lumen, A11, A21 are higher than B11, B21, respectively. False lumen intimal wall pressure of A11, A21 are always higher than the true lumen ones. The variation of the RA can significantly affect the dynamics of blood within the aortic dissection. When the entry tear size is larger than the re-entry tear ones, the false lumen, proximal descending aorta and the wall near re-entry tear are prone to cracking. Entry tear location can significantly alter the hemodynamics of aortic dissection as well. When entry tear location is closer to proximal ascending aorta, false lumen continues to expand and compress the true lumen resulting in the true lumen reduction. For proximal ascending aorta, high pressure in false lumen predicts a higher risk of reverse tear.

Pulse wave imaging in normal, hypertensive and aneurysmal human aortas in vivo: a feasibility study

NASA Astrophysics Data System (ADS)

Li, Ronny X.; Luo, Jianwen; Balaram, Sandhya K.; Chaudhry, Farooq A.; Shahmirzadi, Danial; Konofagou, Elisa E.

2013-07-01

Arterial stiffness is a well-established biomarker for cardiovascular risk, especially in the case of hypertension. The progressive stages of an abdominal aortic aneurysm (AAA) have also been associated with varying arterial stiffness. Pulse wave imaging (PWI) is a noninvasive, ultrasound imaging-based technique that uses the pulse wave-induced arterial wall motion to map the propagation of the pulse wave and measure the regional pulse wave velocity (PWV) as an index of arterial stiffness. In this study, the clinical feasibility of PWI was evaluated in normal, hypertensive, and aneurysmal human aortas. Radiofrequency-based speckle tracking was used to estimate the pulse wave-induced displacements in the abdominal aortic walls of normal (N = 15, mean age 32.5 ± 10.2 years), hypertensive (N = 13, mean age 60.8 ± 15.8 years), and aneurysmal (N = 5, mean age 71.6 ± 11.8 years) human subjects. Linear regression of the spatio-temporal variation of the displacement waveform in the anterior aortic wall over a single cardiac cycle yielded the slope as the PWV and the coefficient of determination r2 as an approximate measure of the pulse wave propagation uniformity. The aortic PWV measurements in all normal, hypertensive, and AAA subjects were 6.03 ± 1.68, 6.69 ± 2.80, and 10.54 ± 6.52 m s-1, respectively. There was no significant difference (p = 0.15) between the PWVs of the normal and hypertensive subjects while the PWVs of the AAA subjects were significantly higher (p < 0.001) compared to those of the other two groups. Also, the average r2 in the AAA subjects was significantly lower (p < 0.001) than that in the normal and hypertensive subjects. These preliminary results suggest that the regional PWV and the pulse wave propagation uniformity (r2) obtained using PWI, in addition to the PWI images and spatio-temporal maps that provide qualitative visualization of the pulse wave, may potentially provide valuable information for the clinical characterization of aneurysms and other vascular pathologies that regionally alter the arterial wall mechanics.

Aortic Valve Disease and Vascular Mechanics: Two-Dimensional Speckle Tracking Echocardiographic Analysis.

PubMed

Leite, Luís; Teixeira, Rogério; Oliveira-Santos, Manuel; Barbosa, António; Martins, Rui; Castro, Graça; Gonçalves, Lino; Pego, Mariano

2016-08-01

Degenerative aortic valve disease (AVD) is a complex disorder that goes beyond valve itself, also undermining aortic wall. We aimed to assess the ascending aortic mechanics with two-dimensional speckle tracking echocardiography (2DSTE) in patients with aortic regurgitation (AR) and hypothesized a relationship with degree of AR. Aortic mechanics were then compared with those of similarly studied healthy controls and patients with aortic stenosis (AS); finally, we aimed to assess the prognostic significance of vascular mechanics in AVD. Overall, 73 patients with moderate-to-severe AR and 22 healthy subjects were enrolled, alongside a previously examined cohort (N = 45) with moderate-to-severe AS. Global circumferential ascending aortic strain (CAAS) and strain rate (CAASR) served as indices of aortic deformation; corrected CAAS was calculated as CAAS/pulse pressure (PP). Median clinical follow-up was 438 days. In patients with severe (vs. moderate) AR, CAASR (1.53 ± 0.29/sec vs. 1.90 ± 0.62/sec, P < 0.05) and corrected CAAS (0.14 ± 0.06%/mmHg vs. 0.19 ± 0.08%/mmHg, P < 0.05) were significantly lower, whereas CAAS did not differ significantly. Measurers of aortic mechanics (CAAS, corrected CAAS, CAASR) differed significantly (all P < 0.01) in patients with AS and AR and in healthy subjects, with lower values seen in patients with AS. In follow-up, survival rate of AVD patients with baseline CAASR >0.88/sec was significantly higher (log rank, 97.4% vs. 73.0%; P = 0.03). Quantitative measures of aortic mechanics were lower for AS patients, suggesting a more significant derangement of aortic elastic properties. In the context of AVD, vascular mechanics assessment proved useful in gauging clinical prognosis. © 2016, Wiley Periodicals, Inc.

Smooth Muscle Cells Isolated from Thoracic Aortic Aneurysms Exhibit Increased Genomic Damage, but Similar Tendency for Apoptosis

PubMed Central

Serhatli, Muge; Kacar, Omer; Adiguzel, Zelal; Tuncer, Altug; Hayran, Mutlu; Baysal, Kemal

2012-01-01

Aortic aneurysms (AA) are characterized by structural deterioration leading to progressive dilation. During the development of AA, two key structural changes are pronounced, one being degradation of extracellular matrix and the other loss of smooth muscle cells (SMCs) through apoptosis. Reactive oxygen species (ROS) are produced above physiological levels in dilated (aneurismal) part of the aorta compared to the nondilated part and they are known to be associated with both the extracellular matrix degradation and the loss of SMCs. In this study, we hypothesized that aneurismal SMCs are more prone to apoptosis and that at least some cells undergo apoptosis due to elevated ROS in the aortic wall. To test this hypothesis, we first isolated SMCs from thoracic aneurismal tissue and compared their apoptotic tendency with normal SMCs in response to H2O2, oxidized sterol, or UV treatment. Exposed cells exhibited morphological changes characteristic of apoptosis, such as cell shrinkage, membrane blebbing, chromatin condensation, and DNA fragmentation. Terminal deoxynucleotidyl transferased UTP nick end labeling (TUNEL) further confirmed the fragmentation of nuclear DNA in these cells. Vascular SMCs were analyzed for their micronuclei (MN) and binucleate (BN) frequency as indicators of genomic abnormality. These data were then compared to patient parameters, including age, gender, hypertension, or aortic diameter for existing correlations. While the tendency for apoptosis was not significantly different compared to normal cells, both the %MN and %BN were higher in aneurismal SMCs. The data suggest that there is increased DNA damage in TAA samples, which might play a pivotal role in disease development. PMID:22871164

The effect of vessel material properties and pulsatile wall motion on the fixation of a proximal stent of an endovascular graft.

PubMed

Corbett, T J; Molony, D S; Callanan, A; McGloughlin, T M

2011-01-01

Migration is a serious failure mechanism associated with endovascular abdominal aortic aneurysm (AAA) repair (EVAR). The effect of vessel material properties and pulsatile wall motion on stent fixation has not been previously investigated. A proximal stent from a commercially available stent graft was implanted into the proximal neck of silicone rubber abdominal aortic aneurysm models of varying proximal neck stiffness (β=25.39 and 20.44). The stent was then dislodged by placing distal force on the stent struts. The peak force to completely dislodge the stent was measured using a loadcell. Dislodgment was performed at ambient pressure with no flow (NF) and during pulsatile flow (PF) at pressures of 120/80 mmHg and 140/100 mmHg to determine if pulsatile wall motions affected the dislodgement force. An imaging analysis was performed at ambient pressure and at pressures of 120 mmHg and 140 mmHg to investigate diameter changes on the model due to the radial force of the stent and internal pressurisation. Stent displacement forces were ~50% higher in the stiffer model (7.16-8.4 N) than in the more compliant model (3.67-4.21 N). The mean displacement force was significantly reduced by 10.95-12.83% from the case of NF to the case of PF at 120/80 mmHg. A further increase in pressure to 140/120 mmHg had no significant effect on the displacement force. The imaging analysis showed that the diameter in the region of the stent was 0.37 mm greater in the less stiff model at all the pressures which could reduce the fixation of the stent. The results suggest that the fixation of passively fixated aortic stents could be comprised in more compliant walls and that pulsatile motions of the wall can reduce the maximum stent fixation. Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.

The effect of simvastatin, aspirin, and their combination in reduction of atheroma plaque

NASA Astrophysics Data System (ADS)

Kurniati, Neng Fisheri; Permatasari, Anita

2015-09-01

Atherosclerosis is one of the risk factors of cardiovascular disease. Atherosclerosis is a chronic inflammatory disease caused by high level of cholesterol especially low density lipoprotein (LDL) and accumulation of neutrophil and macrophage in the artery wall. Thickness of aortic wall is an early stage of atherosclerosis plaque formation. Identification of atherosclerosis plaque formation was done by measuring level of total cholesterol, triglycerides, HDL, LDL, interleukin-18 (IL-18), myeloperoxidase (MPO) and measuring the thickness of aortic wall. Atherosclerosis's model induced by high fat diet and CCT (cholesterol, cholic acid, and propyltiouracil) oral administration. Rats induced cholesterol divided into positive control, simvastatin 25 mg/kg bw, aspirin 20 mg/kg bw, and combination simvastatin 25 mg/kg and aspirin 20 mg/kg bw group for 3 weeks. In the third week, therapy was given to atherosclerosis's model. Then, in the fourth and fifth week, therapy was given but induction of high cholesterol was stopped due to the massive loss of body weight. Total cholesterol, triglycerides, HDL, LDL, MPO, and IL-18 measured by uv-vis spectrophotometry and ELISA. In the end of therapy, aorta's rats was isolated to identify the thickness of aorta wall. In the fourth week, after 1 week of treatment, only combination group showed significantly higher total cholesterol, LDL and MPO compared to positive control group. Level of triglycerides and HDL in all groups did not significantly differ compared to positive control group. After 2 weeks continuing drug treatment, the level of total cholesterol, MPO, and IL-18 were decreased in all groups, and aspirin group showed the lowest level. The level of triglycerides was decreased in simvastatin and aspirin group, and aspirin group showed the lowest. Only combination group showed the lowest level of LDL. Based on histopathology result, the thickness of aortic wall was reduced in all groups and aspirin group showed the lowest.

A simple, effective and clinically applicable method to compute abdominal aortic aneurysm wall stress.

PubMed

Joldes, Grand Roman; Miller, Karol; Wittek, Adam; Doyle, Barry

2016-05-01

Abdominal aortic aneurysm (AAA) is a permanent and irreversible dilation of the lower region of the aorta. It is a symptomless condition that if left untreated can expand to the point of rupture. Mechanically-speaking, rupture of an artery occurs when the local wall stress exceeds the local wall strength. It is therefore desirable to be able to non-invasively estimate the AAA wall stress for a given patient, quickly and reliably. In this paper we present an entirely new approach to computing the wall tension (i.e. the stress resultant equal to the integral of the stresses tangent to the wall over the wall thickness) within an AAA that relies on trivial linear elastic finite element computations, which can be performed instantaneously in the clinical environment on the simplest computing hardware. As an input to our calculations we only use information readily available in the clinic: the shape of the aneurysm in-vivo, as seen on a computed tomography (CT) scan, and blood pressure. We demonstrate that tension fields computed with the proposed approach agree well with those obtained using very sophisticated, state-of-the-art non-linear inverse procedures. Using magnetic resonance (MR) images of the same patient, we can approximately measure the local wall thickness and calculate the local wall stress. What is truly exciting about this simple approach is that one does not need any information on material parameters; this supports the development and use of patient-specific modelling (PSM), where uncertainty in material data is recognised as a key limitation. The methods demonstrated in this paper are applicable to other areas of biomechanics where the loads and loaded geometry of the system are known. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tenascin C protects aorta from acute dissection in mice

PubMed Central

Kimura, Taizo; Shiraishi, Kozoh; Furusho, Aya; Ito, Sohei; Hirakata, Saki; Nishida, Norifumi; Yoshimura, Koichi; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Ikeda, Yasuhiro; Miyamoto, Takanobu; Ueno, Takafumi; Hamano, Kimikazu; Hiroe, Michiaki; Aonuma, Kazutaka; Matsuzaki, Masunori; Imaizumi, Tsutomu; Aoki, Hiroki

2014-01-01

Acute aortic dissection (AAD) is caused by the disruption of intimomedial layer of the aortic walls, which is immediately life-threatening. Although recent studies indicate the importance of proinflammatory response in pathogenesis of AAD, the mechanism to keep the destructive inflammatory response in check is unknown. Here, we report that induction of tenascin-C (TNC) is a stress-evoked protective mechanism against the acute hemodynamic and humoral stress in aorta. Periaortic application of CaCl2 caused stiffening of abdominal aorta, which augmented the hemodynamic stress and TNC induction in suprarenal aorta by angiotensin II infusion. Deletion of Tnc gene rendered mice susceptible to AAD development upon the aortic stress, which was accompanied by impaired TGFβ signaling, insufficient induction of extracellular matrix proteins and exaggerated proinflammatory response. Thus, TNC works as a stress-evoked molecular damper to maintain the aortic integrity under the acute stress. PMID:24514259

Massive aggrecan and versican accumulation in thoracic aortic aneurysm and dissection

PubMed Central

Cikach, Frank S.; Koch, Christopher D.; Mead, Timothy J.; Galatioto, Josephine; Willard, Belinda B.; Emerton, Kelly B.; Eagleton, Matthew J.; Blackstone, Eugene H.; Ramirez, Francesco; Roselli, Eric E.; Apte, Suneel S.

2018-01-01

Proteoglycan accumulation is a hallmark of medial degeneration in thoracic aortic aneurysm and dissection (TAAD). Here, we defined the aortic proteoglycanome using mass spectrometry, and based on the findings, investigated the large aggregating proteoglycans aggrecan and versican in human ascending TAAD and a mouse model of severe Marfan syndrome. The aortic proteoglycanome comprises 20 proteoglycans including aggrecan and versican. Antibodies against these proteoglycans intensely stained medial degeneration lesions in TAAD, contrasting with modest intralamellar staining in controls. Aggrecan, but not versican, was increased in longitudinal analysis of Fbn1mgR/mgR aortas. TAAD and Fbn1mgR/mgR aortas had increased aggrecan and versican mRNAs, and reduced expression of a key proteoglycanase gene, ADAMTS5, was seen in TAAD. Fbn1mgR/mgR mice with ascending aortic dissection and/or rupture had dramatically increased aggrecan staining compared with mice without these complications. Thus, aggrecan and versican accumulation in ascending TAAD occurs via increased synthesis and/or reduced proteolytic turnover, and correlates with aortic dissection/rupture in Fbn1mgR/mgR mice. Tissue swelling imposed by aggrecan and versican is proposed to be profoundly deleterious to aortic wall mechanics and smooth muscle cell homeostasis, predisposing to type-A dissections. These proteoglycans provide potential biomarkers for refined risk stratification and timing of elective aortic aneurysm repair. PMID:29515038

Massive aggrecan and versican accumulation in thoracic aortic aneurysm and dissection.

PubMed

Cikach, Frank S; Koch, Christopher D; Mead, Timothy J; Galatioto, Josephine; Willard, Belinda B; Emerton, Kelly B; Eagleton, Matthew J; Blackstone, Eugene H; Ramirez, Francesco; Roselli, Eric E; Apte, Suneel S

2018-03-08

Proteoglycan accumulation is a hallmark of medial degeneration in thoracic aortic aneurysm and dissection (TAAD). Here, we defined the aortic proteoglycanome using mass spectrometry, and based on the findings, investigated the large aggregating proteoglycans aggrecan and versican in human ascending TAAD and a mouse model of severe Marfan syndrome. The aortic proteoglycanome comprises 20 proteoglycans including aggrecan and versican. Antibodies against these proteoglycans intensely stained medial degeneration lesions in TAAD, contrasting with modest intralamellar staining in controls. Aggrecan, but not versican, was increased in longitudinal analysis of Fbn1mgR/mgR aortas. TAAD and Fbn1mgR/mgR aortas had increased aggrecan and versican mRNAs, and reduced expression of a key proteoglycanase gene, ADAMTS5, was seen in TAAD. Fbn1mgR/mgR mice with ascending aortic dissection and/or rupture had dramatically increased aggrecan staining compared with mice without these complications. Thus, aggrecan and versican accumulation in ascending TAAD occurs via increased synthesis and/or reduced proteolytic turnover, and correlates with aortic dissection/rupture in Fbn1mgR/mgR mice. Tissue swelling imposed by aggrecan and versican is proposed to be profoundly deleterious to aortic wall mechanics and smooth muscle cell homeostasis, predisposing to type-A dissections. These proteoglycans provide potential biomarkers for refined risk stratification and timing of elective aortic aneurysm repair.

Thoracic aorta 3D hemodynamics in pediatric and young adult patients with bicuspid aortic valve.

PubMed

Allen, Bradley D; van Ooij, Pim; Barker, Alex J; Carr, Maria; Gabbour, Maya; Schnell, Susanne; Jarvis, Kelly B; Carr, James C; Markl, Michael; Rigsby, Cynthia; Robinson, Joshua D

2015-10-01

To evaluate the 3D hemodynamics in the thoracic aorta of pediatric and young adult bicuspid aortic valve (BAV) patients. 4D flow MRI was performed in 30 pediatric and young adult BAV patients (age: 13.9 ± 4.4 (range: [3.4, 20.7]) years old, M:F = 17:13) as part of this Institutional Review Board-approved study. Nomogram-based aortic root Z-scores were calculated to assess aortic dilatation and degree of aortic stenosis (AS) severity was assessed on MRI. Data analysis included calculation of time-averaged systolic 3D wall shear stress (WSSsys ) along the entire aorta wall, and regional quantification of maximum and mean WSSsys and peak systolic velocity (velsys ) in the ascending aorta (AAo), arch, and descending aorta (DAo). The 4D flow MRI AAo velsys was also compared with echocardiography peak velocity measurements. There was a positive correlation with both mean and max AAo WSSsys and peak AAo velsys (mean: r = 0.84, P < 0.001, max: r = 0.94, P < 0.001) and AS (mean: rS  = 0.43, P = 0.02, max: rS  = 0.70, P < 0.001). AAo peak velocity was significantly higher when measured with echo compared with 4D flow MRI (2.1 ± 0.98 m/s versus 1.27 ± 0.49 m/s, P < 0.001). In pediatric and young adult patients with BAV, AS and peak ascending aorta velocity are associated with increased AAo WSS, while aortic dilation, age, and body surface area do not significantly impact AAo hemodynamics. Prospective studies are required to establish the role of WSS as a risk-stratification tool in these patients. © 2015 Wiley Periodicals, Inc.

Gradient Echo MRI Characterization of Development of Atherosclerosis in the Abdominal Aorta in Watanabe Heritable Hyperlipidemic Rabbits

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

Wang, Yi-Xiang J., E-mail: yi-xiang.wang@astrazeneca.com; Kuribayashi, Hideto; Wagberg, Maria

Purpose. The Watanabe Heritable Hyperlipidemic (WHHL) rabbit provides an important model of spontaneous atherosclerosis. With a strain of WHHL rabbits which do not develop abdominal aorta lumen stenosis even with advanced atherosclerosis, we studied the MRI-histology correlation, and the natural progression of atherosclerosis in the abdominal aorta. In addition, intra-reader segmentation repeatability and scan-rescan reproducibility were assessed. Methods. Two batches of female WHHL rabbits were used. The first batch of 6 rabbits was scanned at 20 weeks old. A second batch of 17 rabbits was scanned at 50 weeks old and then randomly divided into two subgroups: 8 were killedmore » for histologic investigation; 9 were kept alive for follow-up, with repeat scanning a week later to assess scan-rescan reproducibility, and again at 73 weeks old to assess disease progression. MR images were acquired at 4.7 T using a chemical shift selective fat suppression gradient echo with a saturation band suppressing blood signal within the aortic lumen. Five slices per animal were acquired, centered around the renal artery region of the abdominal aorta, with in-plane resolution of 0.195 mm and slice thickness of 3 mm. Results. The coefficient of variation for intra-reader reproducibility for aortic wall thickness measurements was 2.5% for repeat segmentations of the same scans on the same day, but segmentations of these same scans made 8 months later showed a systematic change, suggesting that intra-reader bias as well as increased variability could compromise assessments made over time. Comparative analyses were therefore performed in one postprocessing session. The coefficient of variation for scan-rescan reproducibility for aortic wall thickness was 5.5% for nine pairs of scans acquired a week apart and segmented on the same day. Good MRI-histology correlation was obtained. The MRI-measured mean aortic wall thickness of animals at 20 weeks of age was 76% that of animals at 50 weeks of age (p < 0.001). There was a small increase in aortic wall thickness between 50 and 73 weeks of age, but this was not significant (p > 0.05). The corresponding differences in lumen cross-sectional areas at 20, 50, and 73 weeks of age were not significant. These results were consistent with in-house historical histology data on this strain of rabbits. Conclusions. High-resolution gradient echo MRI can follow disease progression in the WHHL rabbit spontaneous atherosclerosis disease model.« less

A novel hydrodynamic approach of drag-reducing polymers to improve left ventricular hypertrophy and aortic remodeling in spontaneously hypertensive rats.

PubMed

Zhang, Xinlu; Wang, Xu; Hu, Feng; Zhou, Boda; Chen, Hai-Bin; Zha, Daogang; Liu, Yili; Guo, Yansong; Zheng, Lemin; Xiu, Jiancheng

Drag-reducing polymers (DRPs), when added in minute concentrations, have been shown to decrease peripheral vascular resistance. In this study, the effect of DRPs on the hypertension-induced left ventricular hypertrophy and aortic remodeling was evaluated in spontaneously hypertensive rats (SHR). Male SHR and age-matched Wistar rats were divided into four groups and received intravenous injection of normal saline (NS) or DRPs. Body weight (BW), heart rate (HR) and systolic blood pressure (SBP) were measured. Echocardiography was used to evaluate the changes in left ventricle (LV) function and global wall motion. The LV and aorta were stained by hematoxylin and eosin. Cell size of cardiomyocytes and aortic medial thickness were evaluated for each section. The expression of endothelin-1 (ET-1) of LV and aorta was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. There was no significant difference in the increase of SBP among SHR + NS, SHR + 10DRP and SHR + 20DRP groups. SHR + NS group had markedly smaller left ventricular end-systolic diameter and left ventricular end-diastolic diameter but bigger anterior and posterior systolic wall thicknesses, while there was no significant difference in fractional shortening and ejection fraction. The cross-sectional areas (CSAs) of cardiomyocytes and the medial thickness of the aorta in SHR + 10 (ppm) DRP and SHR + 20 (ppm) DRP groups were significantly reduced compared with SHR + NS group. The expression of ET-1 in SHR + 10DRP and SHR + 20DRP groups was significantly attenuated. These results suggest that chronic treatment with DRPs can protect against left ventricular hypertrophy and aortic remodeling. DRPs may offer a new approach to the treatment of left ventricular hypertrophy and aortic remodeling caused by hypertension.

A novel hydrodynamic approach of drag-reducing polymers to improve left ventricular hypertrophy and aortic remodeling in spontaneously hypertensive rats

PubMed Central

Zhang, Xinlu; Wang, Xu; Hu, Feng; Zhou, Boda; Chen, Hai-Bin; Zha, Daogang; Liu, Yili; Guo, Yansong; Zheng, Lemin; Xiu, Jiancheng

2016-01-01

Drag-reducing polymers (DRPs), when added in minute concentrations, have been shown to decrease peripheral vascular resistance. In this study, the effect of DRPs on the hypertension-induced left ventricular hypertrophy and aortic remodeling was evaluated in spontaneously hypertensive rats (SHR). Male SHR and age-matched Wistar rats were divided into four groups and received intravenous injection of normal saline (NS) or DRPs. Body weight (BW), heart rate (HR) and systolic blood pressure (SBP) were measured. Echocardiography was used to evaluate the changes in left ventricle (LV) function and global wall motion. The LV and aorta were stained by hematoxylin and eosin. Cell size of cardiomyocytes and aortic medial thickness were evaluated for each section. The expression of endothelin-1 (ET-1) of LV and aorta was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. There was no significant difference in the increase of SBP among SHR + NS, SHR + 10DRP and SHR + 20DRP groups. SHR + NS group had markedly smaller left ventricular end-systolic diameter and left ventricular end-diastolic diameter but bigger anterior and posterior systolic wall thicknesses, while there was no significant difference in fractional shortening and ejection fraction. The cross-sectional areas (CSAs) of cardiomyocytes and the medial thickness of the aorta in SHR + 10 (ppm) DRP and SHR + 20 (ppm) DRP groups were significantly reduced compared with SHR + NS group. The expression of ET-1 in SHR + 10DRP and SHR + 20DRP groups was significantly attenuated. These results suggest that chronic treatment with DRPs can protect against left ventricular hypertrophy and aortic remodeling. DRPs may offer a new approach to the treatment of left ventricular hypertrophy and aortic remodeling caused by hypertension. PMID:28008249

Role of Re-entry Tears on the Dynamics of Type B Dissection Flap.

PubMed

Canchi, Saranya; Guo, Xiaomei; Phillips, Matt; Berwick, Zachary; Kratzberg, Jarin; Krieger, Joshua; Roeder, Blayne; Haulon, Stephan; Chambers, Sean; Kassab, Ghassan S

2018-01-01

Mortality during follow-up after acute Type B aortic dissection is substantial with aortic expansion observed in over 59% of the patients. Lumen pressure differential is considered a prime contributing factor for aortic dilation after propagation. The objective of the study was to evaluate the relationship between changes in vessel geometry with and without lumen pressure differential post propagation in an ex vivo porcine model with comparison with patient clinical data. A pulse duplicator system was utilized to propagate the dissection within descending thoracic porcine aortic vessels for set proximal (%circumference of the entry tear: 40%, axial length: 2 cm) and re-entry (50% of distal vessel circumference) tear geometry. Measurements of lumen pressure differential were made along with quantification of vessel geometry (n = 16). The magnitude of mean lumen pressure difference measured after propagation was low (~ 5 mmHg) with higher pressures measured in false lumen and as anticipated the pressure difference approached zero after the creation of distal re-entry tear. False lumen Dissection Ratio (FDR) defined as arc length of dissected wall divided by arc length of dissection flap, had mean value of 1.59 ± 0.01 at pressure of 120/80 mmHg post propagation with increasing values with increase in pulse pressure that was not rescued with the creation of distal re-entry tear (p < 0.01). An average FDR of 1.87 ± 0.27 was measured in patients with acute Type B dissection. Higher FDR value (FDR = 1 implies zero dissection) in the presence of distal re-entry tear demonstrates an acute change in vessel morphology in response to the dissection independent of local pressure changes challenges the re-apposition of the aortic wall.

Chronic hypertension increases aortic endothelial hydraulic conductivity by upregulating endothelial aquaporin-1 expression.

PubMed

Toussaint, Jimmy; Raval, Chirag Bharavi; Nguyen, Tieuvi; Fadaifard, Hadi; Joshi, Shripad; Wolberg, George; Quarfordt, Steven; Jan, Kung-Ming; Rumschitzki, David S

2017-11-01

Numerous studies have examined the role of aquaporins in osmotic water transport in various systems, but virtually none have focused on the role of aquaporin in hydrostatically driven water transport involving mammalian cells save for our laboratory's recent study of aortic endothelial cells. Here, we investigated aquaporin-1 expression and function in the aortic endothelium in two high-renin rat models of hypertension, the spontaneously hypertensive genetically altered Wistar-Kyoto rat variant and Sprague-Dawley rats made hypertensive by two-kidney, one-clip Goldblatt surgery. We measured aquaporin-1 expression in aortic endothelial cells from whole rat aortas by quantitative immunohistochemistry and function by measuring the pressure-driven hydraulic conductivities of excised rat aortas with both intact and denuded endothelia on the same vessel. We used them to calculate the effective intimal hydraulic conductivity, which is a combination of endothelial and subendothelial components. We observed well-correlated enhancements in aquaporin-1 expression and function in both hypertensive rat models as well as in aortas from normotensive rats whose expression was upregulated by 2 h of forskolin treatment. Upregulated aquaporin-1 expression and function may be a response to hypertension that critically determines conduit artery vessel wall viability and long-term susceptibility to atherosclerosis. NEW & NOTEWORTHY The aortic endothelia of two high-renin hypertensive rat models express greater than two times the aquaporin-1 and, at low pressures, have greater than two times the endothelial hydraulic conductivity of normotensive rats. Data are consistent with theory predicting that higher endothelial aquaporin-1 expression raises the critical pressure for subendothelial intima compression and for artery wall hydraulic conductivity to drop. Copyright © 2017 the American Physiological Society.

Chest pain in patients with arterial hypertension, angiographically normal coronary arteries and stiff aorta: the aortic pain syndrome.

PubMed

Stakos, Dimitrios A; Tziakas, Dimitrios N; Chalikias, George; Mitrousi, Konstantina; Tsigalou, Christina; Boudoulas, Harisios

2013-01-01

Arterial hypertension is often associated with a stiff aorta as a result of collagen accumulation in the aortic wall and may produce chest pain. In the present study, possible interrelationships between aortic function, collagen turnover and exercise-induced chest pain in patients with arterial hypertension and angiographically normal coronary arteries were investigated. Ninety-seven patients with arterial hypertension, angiographically normal coronary arteries and no evidence of myocardial ischemia on nuclear cardiac imaging during exercise test were studied. Of these, 43 developed chest pain during exercise (chest pain group) while 54 did not (no chest pain group). Carotid femoral pulse-wave velocity (PWVc-f) was used to assess the elastic properties of the aorta. Amino-terminal pro-peptides of pro-collagen type I, (PINP, reflecting collagen synthesis), serum telopeptides of collagen type I (CITP, reflecting collagen degradation), pro-metalloproteinase 1 (ProMMP-1), and tissue inhibitor of metalloproteinase 1 (TIMP-1, related to collagen turnover) were measured in plasma by immunoassay. The chest pain group had higher PWVc-f, higher and /CITP ratio, and lower proMMP-1/ TIMP-1 ratio compared to the no chest pain group. PWVc-f (t=2.53, p=0.02) and PINP (t=2.42, p=0.02) were independently associated with the presence of chest pain in multiple regression analysis. Patients with arterial hypertension, exercise-induced chest pain and angiographically normal coronary arteries, without evidence of exercise-induced myocardial ischemia, had a stiffer aorta compared to those without chest pain. Alterations in collagen type I turnover that favor collagen accumulation in the aortic wall may contribute to aortic stiffening and chest pain in these patients.

Protection from cigarette smoke-induced vascular injury by recombinant human relaxin-2 (serelaxin).

PubMed

Pini, Alessandro; Boccalini, Giulia; Baccari, Maria Caterina; Becatti, Matteo; Garella, Rachele; Fiorillo, Claudia; Calosi, Laura; Bani, Daniele; Nistri, Silvia

2016-05-01

Smoking is regarded as a major risk factor for the development of cardiovascular diseases (CVD). This study investigates whether serelaxin (RLX, recombinant human relaxin-2) endowed with promising therapeutic properties in CVD, can be credited of a protective effect against cigarette smoke (CS)-induced vascular damage and dysfunction. Guinea pigs exposed daily to CS for 8 weeks were treated with vehicle or RLX, delivered by osmotic pumps at daily doses of 1 or 10 μg. Controls were non-smoking animals. Other studies were performed on primary guinea pig aortic endothelial (GPAE) cells, challenged with CS extracts (CSE) in the absence and presence of 100 ng/ml (17 nmol/l) RLX. In aortic specimens from CS-exposed guinea pigs, both the contractile and the relaxant responses to phenylephrine and acetylcholine, respectively, were significantly reduced in amplitude and delayed, in keeping with the observed adverse remodelling of the aortic wall, endothelial injury and endothelial nitric oxide synthase (eNOS) down-regulation. RLX at both doses maintained the aortic contractile and relaxant responses to a control-like pattern and counteracted aortic wall remodelling and endothelial derangement. The experiments with GPAE cells showed that CSE significantly decreased cell viability and eNOS expression and promoted apoptosis by sparkling oxygen free radical-related cytotoxicity, while RLX counterbalanced the adverse effects of CSE. These findings demonstrate that RLX is capable of counteracting CS-mediated vascular damage and dysfunction by reducing oxidative stress, thus adding a tile to the growing mosaic of the beneficial effects of RLX in CVD. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Numerical analysis of wall shear stress in ascending aorta before tearing in type A aortic dissection.

PubMed

Chi, Qingzhuo; He, Ying; Luan, Yong; Qin, Kairong; Mu, Lizhong

2017-10-01

Although the incidence of many cardiovascular diseases has declined as medical treatments have improved, the prevalence of aortic dissection (AD) has increased. Compared to type B dissections, type A dissections are more severe, and most patients with type A dissections require surgical treatment. The objective of this study was to investigate the relationships between the wall shear stress (WSS) on the aortic endothelium and the frequent tearing positions using computational fluid dynamics. Five type A dissection cases and two normal aortas were included in the study. First, the structures of the aortas before the type A dissection were reconstructed on the basis of the original imaging data. Analyses of flow in the reconstructed premorbid structures reveals that the rupture positions in three of the five cases corresponded to the area of maximum elevated WSS. Moreover, the WSS at the junction of the aortic arch and descending aorta was found to be elevated, which is considered to be related to the locally disturbed helical flow. Meanwhile, the highest WSS in the patients with premorbid AD was found to be almost double that of the control group. Due to the noticeable morphological differences between the AD cases and the control group, the WSSs in the premorbid structures without vasodilation in the ascending part were estimated. The computational results revealed that the WSS was lower in the aorta without vasodilation, but the pressure drop in this situation was higher than that with vasodilation in the ascending aorta. Significant differences were seen between the AD cases and the control group in the angles of the side branches of the aortic arch and its bending degree. Dilation of the ascending aorta and alterations in the branching angles may be the key determinants of a high WSS that leads to type A dissection. Greater tortuosity of the aortic arch leads to stronger helical flow through the distal aortic arch, which may be related to tears in this region. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Relation Between Near-Wall Particle-Hemodynamics and Onset of Thrombus Formation in Abdominal Aortic Aneurysms

PubMed Central

Basciano, C.; Kleinstreuer, C.; Hyun, S.; Finol, E. A.

2014-01-01

A novel computational particle-hemodynamics analysis of key criteria for the onset of an intraluminal thrombus (ILT) in a patient-specific abdominal aortic aneurysm (AAA) is presented. The focus is on enhanced platelet and white blood cell residence times as well as their elevated surface-shear loads in near-wall regions of the AAA sac. The generalized results support the hypothesis that a patient's AAA geometry and associated particle-hemodynamics have the potential to entrap activated blood particles, which will play a role in the onset of ILT. Although the ILT history of only a single patient was considered, the modeling and simulation methodology provided allow for the development of an efficient computational tool to predict the onset of ILT formation in complex patient-specific cases. PMID:21373952

A Hybrid Windkessel Model of Blood Flow in Arterial Tree Using Velocity Profile Method

NASA Astrophysics Data System (ADS)

Aboelkassem, Yasser; Virag, Zdravko

2016-11-01

For the study of pulsatile blood flow in the arterial system, we derived a coupled Windkessel-Womersley mathematical model. Initially, a 6-elements Windkessel model is proposed to describe the hemodynamics transport in terms of constant resistance, inductance and capacitance. This model can be seen as a two compartment model, in which the compartments are connected by a rigid pipe, modeled by one inductor and resistor. The first viscoelastic compartment models proximal part of the aorta, the second elastic compartment represents the rest of the arterial tree and aorta can be seen as the connection pipe. Although the proposed 6-elements lumped model was able to accurately reconstruct the aortic pressure, it can't be used to predict the axial velocity distribution in the aorta and the wall shear stress and consequently, proper time varying pressure drop. We then modified this lumped model by replacing the connection pipe circuit elements with a vessel having a radius R and a length L. The pulsatile flow motions in the vessel are resolved instantaneously along with the Windkessel like model enable not only accurate prediction of the aortic pressure but also wall shear stress and frictional pressure drop. The proposed hybrid model has been validated using several in-vivo aortic pressure and flow rate data acquired from different species such as, humans, dogs and pigs. The method accurately predicts the time variation of wall shear stress and frictional pressure drop. Institute for Computational Medicine, Dept. Biomedical Engineering.

Turbulence significantly increases pressure and fluid shear stress in an aortic aneurysm model under resting and exercise flow conditions.

PubMed

Khanafer, Khalil M; Bull, Joseph L; Upchurch, Gilbert R; Berguer, Ramon

2007-01-01

The numerical models of abdominal aortic aneurysm (AAA) in use do not take into account the non-Newtonian behavior of blood and the development of local turbulence. This study examines the influence of pulsatile, turbulent, non-Newtonian flow on fluid shear stresses and pressure changes under rest and exercise conditions. We numerically analyzed pulsatile turbulent flow, using simulated physiological rest and exercise waveforms, in axisymmetric-rigid aortic aneurysm models (AAMs). Discretization of governing equations was achieved using a finite element scheme. Maximum turbulence-induced shear stress was found at the distal end of an AAM. In large AAMs (dilated to undilated diameter ratio = 3.33) at peak systolic flow velocity, fluid shear stress during exercise is 70.4% higher than at rest. Our study provides a numerical, noninvasive method for obtaining detailed data on the forces generated by pulsatile turbulent flow in AAAs that are difficult to study in humans and in physical models. Our data suggest that increased flow turbulence results in increased shear stress in aneurysms. While pressure readings are fairly uniform along the length of an aneurysm, the kinetic energy generated by turbulence impacting on the wall of the distal half of the aneurysm increases fluid and wall shear stress at this site. If the increased fluid shear stress results in further dilation and hence further turbulence, wall stress may be a mechanism for aneurysmal growth and eventual rupture.

Abdominal aortic atherosclerosis at MR imaging is associated with cardiovascular events: the Dallas heart study.

PubMed

Maroules, Christopher D; Rosero, Eric; Ayers, Colby; Peshock, Ronald M; Khera, Amit

2013-10-01

To determine the value of two abdominal aortic atherosclerosis measurements at magnetic resonance (MR) imaging for predicting future cardiovascular events. This study was approved by the institutional review board and complied with HIPAA regulations. The study consisted of 2122 participants from the multiethnic, population-based Dallas Heart Study who underwent abdominal aortic MR imaging at 1.5 T. Aortic atherosclerosis was measured by quantifying mean aortic wall thickness (MAWT) and aortic plaque burden. Participants were monitored for cardiovascular death, nonfatal cardiac events, and nonfatal extracardiac vascular events over a mean period of 7.8 years ± 1.5 (standard deviation [SD]). Cox proportional hazards regression was used to assess independent associations of aortic atherosclerosis and cardiovascular events. Increasing MAWT was positively associated with male sex (odds ratio, 3.66; P < .0001), current smoking (odds ratio, 2.53; P < .0001), 10-year increase in age (odds ratio, 2.24; P < .0001), and hypertension (odds ratio, 1.66; P = .0001). A total of 143 participants (6.7%) experienced a cardiovascular event. MAWT conferred an increased risk for composite events (hazard ratio, 1.28 per 1 SD; P = .001). Aortic plaque was not associated with increased risk for composite events. Increasing MAWT and aortic plaque burden both conferred an increased risk for nonfatal extracardiac events (hazard ratio of 1.52 per 1 SD [P < .001] and hazard ratio of 1.46 per 1 SD [P = .03], respectively). MR imaging measures of aortic atherosclerosis are predictive of future adverse cardiovascular events. © RSNA, 2013.

Smad4 Deficiency in Smooth Muscle Cells Initiates the Formation of Aortic Aneurysm.

PubMed

Zhang, Peng; Hou, Siyuan; Chen, Jicheng; Zhang, Jishuai; Lin, Fuyu; Ju, Renjie; Cheng, Xuan; Ma, Xiaowei; Song, Yao; Zhang, Youyi; Zhu, Minsheng; Du, Jie; Lan, Yu; Yang, Xiao

2016-02-05

Aortic aneurysm is a life-threatening cardiovascular disorder caused by the predisposition for dissection and rupture. Genetic studies have proved the involvement of the transforming growth factor-β (TGF-β) pathway in aortic aneurysm. Smad4 is the central mediator of the canonical TGF-β signaling pathway. However, the exact role of Smad4 in smooth muscle cells (SMCs) leading to the pathogenesis of aortic aneurysms is largely unknown. To determine the role of smooth muscle Smad4 in the pathogenesis of aortic aneurysms. Conditional gene knockout strategy combined with histology and expression analysis showed that Smad4 or TGF-β receptor type II deficiency in SMCs led to the occurrence of aortic aneurysms along with an upregulation of cathepsin S and matrix metallopeptidase-12, which are proteases essential for elastin degradation. We further demonstrated a previously unknown downregulation of matrix metallopeptidase-12 by TGF-β in the aortic SMCs, which is largely abrogated in the absence of Smad4. Chemotactic assay and pharmacologic treatment demonstrated that Smad4-deficient SMCs directly triggered aortic wall inflammation via the excessive production of chemokines to recruit macrophages. Monocyte/macrophage depletion or blocking selective chemokine axis largely abrogated the progression of aortic aneurysm caused by Smad4 deficiency in SMCs. The findings reveal that Smad4-dependent TGF-β signaling in SMCs protects against aortic aneurysm formation and dissection. The data also suggest important implications for novel therapeutic strategies to limit the progression of the aneurysm resulting from TGF-β signaling loss-of-function mutations. © 2015 American Heart Association, Inc.

Arterial switch: translocation of the intramural coronary artery.

PubMed

Asou, T; Karl, T R; Pawade, A; Mee, R B

1994-02-01

Translocation of an intramural coronary artery is one of the most challenging problems in anatomic correction of transposition of the great arteries. Of 259 patients undergoing arterial switch procedure for transposition of the great arteries in our hospital, 12 (4.6%) were found to have intramural coronary arteries. The diagnosis was made intraoperatively in all patients. There were five different types of intramural coronary anatomy noted, with ostial stenosis present in half. The operative technique consisted of detachment of the posterior commissure of the aortic valve and unroofing of the intramural segment of the coronary artery by excision of a triangular portion of internal aortic wall. The coronary arteries were excised as a single disc, which was divided into two cuffs. The arterial switch was then performed in the usual fashion. The posterior commissure of the aortic valve was resuspended to the pericardial patch used to reconstruct the neopulmonary artery sinus. There were no operative or late deaths over a follow-up of 328 patient-months. Postoperatively, no patient showed ischemic changes on electrocardiogram or abnormal wall motion on echocardiogram. We believe that intramural coronary arteries can be managed satisfactorily with this technique, and that arterial switch will be possible in all cases.

Patient-specific finite element analysis of ascending aorta aneurysms

PubMed Central

Martin, Caitlin; Elefteriades, John

2015-01-01

Catastrophic ascending aorta aneurysm (AsAA) dissection and rupture can be prevented by elective surgical repair, but identifying individuals at risk remains a challenge. Typically the decision to operate is based primarily on the overall aneurysm size, which may not be a reliable indicator of risk. In this study, AsAA inflation and rupture was simulated in 27 patient-specific finite element models constructed from clinical CT imaging data and tissue mechanical testing data from matching patients. These patients included n = 8 with concomitant bicuspid aortic valve (BAV), n = 10 with bovine aortic arch (BAA), and n = 10 with neither BAV nor BAA. AsAA rupture risk was found to increase with elevated systolic wall stress and tissue stiffness. The aortic size index was sufficient for identifying the patients with the lowest risk of rupture, but unsuitable for delineating between patients at moderate and high risk. There was no correlation between BAV or BAA and AsAA rupture risk; however, the AsAA morphology was different among these patients. These results support the use of mechanical parameters such as vessel wall stress and tissue stiffness for AsAA presurgical evaluation. PMID:25770248

A new self-expandable aortic valved stent deployed above native leaflets for aortic insufficiency: an in vitro study.

PubMed

Huang, H; Zhou, Y; Shao, J; Cai, J; Mei, Y; Wang, Y

2012-12-01

The aim of this paper was to develop a new self-expandable aortic valved stent following the shape of the sinus of Valsalva, which can be deployed above native leaflets for aortic regurgitation, and study it's effect on coronary artery flow when orthotopic implantation in and above native leaflets. New self-expandable aortic valved stent consist of nitinol stent and bovine pericardium, and was designed following the shape of the sinus of Valsalva, the bovine pericardium was tailed as native leaflet. Thirty-six swine hearts were divided into three equal groups of twelve. In Group A (N.=12), the new self-expandable aortic valved stents deployed in native leaflets. In Group B (N.=12), the new self-expandable aortic valved stents deployed above native leaflets. In Group C (N.=12), the cylinder-like valved stents deployed only in native leaflets. The measurements of each coronary flow rate and endoscopic inspections were repeated post-implantation. In Group A and C, valve implantation in native leaflets resulted in a significant decrease in both left and right coronary flows. In Group B, no significant change in either right or left coronary flow was found after new self-expandable aortic valved stent placement. Endoscopic inspections showed that in group A and C the native leaflets sandwiched between valved stent and aortic wall, whereas, in group B the native leaflets were under the artificial leaflets. Two kinds of stents deployed in native leaflets affect left and right coronary flows significantly. No significant effect was found when the new self-expandable aortic valved stent deployed above native leaflets. This new self-expandable aortic valved stent can be deployed above the native leaflets, which avoids the obstruction of native leaflets on coronary flow.

Resveratrol Inhibits Aortic Root Dilatation in the Fbn1C1039G/+ Marfan Mouse Model.

PubMed

Hibender, Stijntje; Franken, Romy; van Roomen, Cindy; Ter Braake, Anique; van der Made, Ingeborg; Schermer, Edith E; Gunst, Quinn; van den Hoff, Maurice J; Lutgens, Esther; Pinto, Yigal M; Groenink, Maarten; Zwinderman, Aeilko H; Mulder, Barbara J M; de Vries, Carlie J M; de Waard, Vivian

2016-08-01

Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the fibrillin-1 gene. Patients with MFS are at risk of aortic aneurysm formation and dissection. Usually, blood pressure-lowering drugs are used to reduce aortic events; however, this is not sufficient for most patients. In the aorta of smooth muscle cell-specific sirtuin-1-deficient mice, spontaneous aneurysm formation and senescence are observed. Resveratrol is known to enhance sirtuin-1 activity and to reduce senescence, which prompted us to investigate the effectiveness of resveratrol in inhibition of aortic dilatation in the Fbn1(C1039G/+) MFS mouse model. Aortic senescence strongly correlates with aortic root dilatation rate in MFS mice. However, although resveratrol inhibits aortic dilatation, it only shows a trend toward reduced aortic senescence. Resveratrol enhances nuclear localization of sirtuin-1 in the vessel wall and, in contrast to losartan, does not affect leukocyte infiltration nor activation of SMAD2 and extracellular signal-regulated kinases 1/2 (ERK1/2). Interestingly, specific sirtuin-1 activation (SRT1720) or inhibition (sirtinol) in MFS mice does not affect aortic root dilatation rate, although senescence is changed. Resveratrol reduces aortic elastin breaks and decreases micro-RNA-29b expression coinciding with enhanced antiapoptotic Bcl-2 expression and decreased number of terminal apoptotic cells. In cultured smooth muscle cells, the resveratrol effect on micro-RNA-29b downregulation is endothelial cell and nuclear factor κB-dependent. Resveratrol inhibits aortic root dilatation in MFS mice by promoting elastin integrity and smooth muscle cell survival, involving downregulation of the aneurysm-related micro-RNA-29b in the aorta. On the basis of these data, resveratrol holds promise as a novel intervention strategy for patients with MFS. © 2016 The Authors.

Resveratrol Inhibits Aortic Root Dilatation in the Fbn1C1039G/+ Marfan Mouse Model

PubMed Central

Hibender, Stijntje; Franken, Romy; van Roomen, Cindy; ter Braake, Anique; van der Made, Ingeborg; Schermer, Edith E.; Gunst, Quinn; van den Hoff, Maurice J.; Lutgens, Esther; Pinto, Yigal M.; Groenink, Maarten; Zwinderman, Aeilko H.; Mulder, Barbara J.M.; de Vries, Carlie J.M.

2016-01-01

Objective— Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the fibrillin-1 gene. Patients with MFS are at risk of aortic aneurysm formation and dissection. Usually, blood pressure–lowering drugs are used to reduce aortic events; however, this is not sufficient for most patients. In the aorta of smooth muscle cell–specific sirtuin-1–deficient mice, spontaneous aneurysm formation and senescence are observed. Resveratrol is known to enhance sirtuin-1 activity and to reduce senescence, which prompted us to investigate the effectiveness of resveratrol in inhibition of aortic dilatation in the Fbn1C1039G/+ MFS mouse model. Approach and Results— Aortic senescence strongly correlates with aortic root dilatation rate in MFS mice. However, although resveratrol inhibits aortic dilatation, it only shows a trend toward reduced aortic senescence. Resveratrol enhances nuclear localization of sirtuin-1 in the vessel wall and, in contrast to losartan, does not affect leukocyte infiltration nor activation of SMAD2 and extracellular signal–regulated kinases 1/2 (ERK1/2). Interestingly, specific sirtuin-1 activation (SRT1720) or inhibition (sirtinol) in MFS mice does not affect aortic root dilatation rate, although senescence is changed. Resveratrol reduces aortic elastin breaks and decreases micro-RNA-29b expression coinciding with enhanced antiapoptotic Bcl-2 expression and decreased number of terminal apoptotic cells. In cultured smooth muscle cells, the resveratrol effect on micro-RNA-29b downregulation is endothelial cell and nuclear factor κB-dependent. Conclusions— Resveratrol inhibits aortic root dilatation in MFS mice by promoting elastin integrity and smooth muscle cell survival, involving downregulation of the aneurysm-related micro-RNA-29b in the aorta. On the basis of these data, resveratrol holds promise as a novel intervention strategy for patients with MFS. PMID:27283746

Morphotype-Dependent Flow Characteristics in Bicuspid Aortic Valve Ascending Aortas: A Benchtop Particle Image Velocimetry Study

PubMed Central

McNally, Andrew; Madan, Ashish; Sucosky, Philippe

2017-01-01

The bicuspid aortic valve (BAV) is a major risk factor for secondary aortopathy such as aortic dilation. The heterogeneous BAV morphotypes [left-right-coronary cusp fusion (LR), right-non-coronary cusp fusion (RN), and left-non-coronary cusp fusion (LN)] are associated with different dilation patterns, suggesting a role for hemodynamics in BAV aortopathogenesis. However, assessment of this theory is still hampered by the limited knowledge of the hemodynamic abnormalities generated by the distinct BAV morphotypes. The objective of this study was to compare experimentally the hemodynamics of a normal (i.e., non-dilated) ascending aorta (AA) subjected to tricuspid aortic valve (TAV), LR-BAV, RN-BAV, and NL-BAV flow. Tissue BAVs reconstructed from porcine TAVs were subjected to physiologic pulsatile flow conditions in a left-heart simulator featuring a realistic aortic root and compliant aorta. Phase-locked particle image velocimetry experiments were carried out to characterize the flow in the aortic root and in the tubular AA in terms of jet skewness and displacement, as well as mean velocity, viscous shear stress and Reynolds shear stress fields. While all three BAVs generated skewed and asymmetrical orifice jets (up to 1.7- and 4.0-fold increase in flow angle and displacement, respectively, relative to the TAV at the sinotubular junction), the RN-BAV jet was out of the plane of observation. The LR- and NL-BAV exhibited a 71% increase in peak-systolic orifice jet velocity relative to the TAV, suggesting an inherent degree of stenosis in BAVs. While these two BAV morphotypes subjected the convexity of the aortic wall to viscous shear stress overloads (1.7-fold increase in maximum peak-systolic viscous shear stress relative to the TAV-AA), the affected sites were morphotype-dependent (LR-BAV: proximal AA, NL-BAV: distal AA). Lastly, the LR- and NL-BAV generated high degrees of turbulence in the AA (up to 2.3-fold increase in peak-systolic Reynolds shear stress relative to the TAV) that were sustained from peak systole throughout the deceleration phase. This in vitro study reveals substantial flow abnormalities (increased jet skewness, asymmetry, jet velocity, turbulence, and shear stress overloads) in non-dilated BAV aortas, which differ from those observed in dilated aortas but still coincide with aortic wall regions prone to dilation. PMID:28203207

Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue.

PubMed

Holsti, Mari; Wanhainen, Anders; Lundin, Christina; Björck, Martin; Tegler, Gustaf; Svensson, Johan; Sund, Malin

2018-04-12

Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised. This was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta ≤ 25 mm, 2) sub-aneurysmal aorta (SAA) 26-29 mm, and 3) AAA ≥ 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence. Plasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue. Plasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Detection of Aortic Wall Inclusion Using Regional Pulse Wave Propagation and Velocity In Silico

PubMed Central

Shahmirzadi, Danial; Konofagou, Elisa E.

2012-01-01

Monitoring of the regional stiffening of the arterial wall may prove important in the diagnosis of various vascular pathologies. The pulse wave velocity (PWV) along the aortic wall has been shown to be dependent on the wall stiffness and has played a fundamental role in a range of diagnostic methods. Conventional clinical methods involve a global examination of the pulse traveling between two remote sites, e.g. femoral and carotid arteries, to provide an average PWV estimate. However, the majority of vascular diseases entail regional vascular changes and therefore may not be detected by a global PWV estimate. In this paper, a fluid-structure interaction study of straight-geometry aortas was carried out to examine the effects of regional stiffness changes on PWV. Five homogeneous aortas with increasing wall stiffness as well as two aortas with soft and hard inclusions were considered. In each case, spatio-temporal maps of the wall motion were used to analyze the regional pulse wave propagation. On the homogeneous aortas, increasing PWVs were found to increase with the wall moduli (R2 = 0.9988), indicating the reliability of the model to accurately represent the wave propagation. On the inhomogeneous aortas, formation of reflected and standing waves was observed at the site of the hard and soft inclusions, respectively. Neither the hard nor the soft inclusion had a significant effect on the velocity of the traveling pulse beyond the inclusion site, which supported the hypothesis that a global measurement of the average PWV could fail to detect regional abnormalities. PMID:24235978

Anatomical Confirmation of Computed Tomography-Based Diagnosis of the Atherosclerosis Discovered in 17th Century Korean Mummy

PubMed Central

Kim, Myeung Ju; Kim, Yi-Suk; Oh, Chang Seok; Go, Jai-Hyang; Lee, In Sun; Park, Won-Kyu; Cho, Seok-Min; Kim, Soon-Kwan; Shin, Dong Hoon

2015-01-01

In the present study on a newly discovered 17th century Korean mummy, computed tomography (CT) revealed multiple aortic calcifications within the aortic wall that were indicative of ancient atherosclerosis. The CT-based findings were confirmed by our subsequent post-factum dissection, which exhibited possible signs of the disease including ulcerated plaques, ruptured hemorrhages, and intimal thickening where the necrotic core was covered by the fibrous cap. These findings are strong indicators that the mummy suffered from aortic atherosclerosis during her lifetime. The present study is a good example of how CT images of vascular calcifications can be a useful diagnostic tool in forming at least preliminary diagnoses of ancient atherosclerosis. PMID:25816014

The Abdominal Aortic Aneurysm and Intraluminal Thrombus: Current Concepts of Development and Treatment

PubMed Central

Piechota-Polanczyk, Aleksandra; Jozkowicz, Alicja; Nowak, Witold; Eilenberg, Wolf; Neumayer, Christoph; Malinski, Tadeusz; Huk, Ihor; Brostjan, Christine

2015-01-01

The pathogenesis of the abdominal aortic aneurysm (AAA) shows several hallmarks of atherosclerotic and atherothrombotic disease, but comprises an additional, predominant feature of proteolysis resulting in the degradation and destabilization of the aortic wall. This review aims to summarize the current knowledge on AAA development, involving the accumulation of neutrophils in the intraluminal thrombus and their central role in creating an oxidative and proteolytic environment. Particular focus is placed on the controversial role of heme oxygenase 1/carbon monoxide and nitric oxide synthase/peroxynitrite, which may exert both protective and damaging effects in the development of the aneurysm. Treatment indications as well as surgical and pharmacological options for AAA therapy are discussed in light of recent reports. PMID:26664891

Subclinical atherosclerosis and subsequent cognitive function

PubMed Central

Rossetti, Heidi C.; Weiner, Myron; Hynan, Linda S.; Cullum, C. Munro; Khera, Amit; Lacritz, Laura H.

2016-01-01

Objective To examine the relationship between measures of subclinical atherosclerosis and subsequent cognitive function. Method Participants from the Dallas Heart Study (DHS), a population-based multiethnic study of cardiovascular disease pathogenesis, were re-examined 8 years later (DHS-2) with the Montreal Cognitive Assessment (MoCA); N = 1904, mean age = 42.9, range 8–65. Associations of baseline measures of subclinical atherosclerosis (coronary artery calcium, abdominal aortic plaque, and abdominal aortic wall thickness) with MoCA scores measured at follow-up were examined in the group as a whole and in relation to age and ApoE4 status. Results A significant linear trend of successively lower MoCA scores with increasing numbers of atherosclerotic indicators was observed (F(3, 1150) = 5.918, p = .001). CAC was weakly correlated with MoCA scores (p = .047) and MoCA scores were significantly different between participants with and without CAC (M = 22.35 vs 23.69, p = 0.038). With the exception of a small association between abdominal AWT and MoCA in subjects over age 50, abdominal AWT and abdominal aortic plaque did not correlate with MoCA total score (p ≥.052). Cognitive scores and atherosclerosis measures were not impacted by ApoE4 status (p ≥.455). Conclusion In this ethnically diverse population-based sample, subclinical atherosclerosis was minimally associated with later cognitive function in middle-aged adults. PMID:25957568

Successful transfemoral aortic Edwards(®) SAPIEN(®) bioprosthesis implantation without using iodinated contrast media in a woman with severe allergy to contrast agent.

PubMed

Leroux, Lionel; Dijos, Marina; Dos Santos, Pierre

2013-12-01

Severe anaphylactoid reaction after the use of iodinated contrast media are rare but can contraindicate the use of contrast agent. It was the case of a 53-year-old woman suffering from symptomatic severe aortic stenosis, recused for cardiac surgery because of deleterious effects of chest-wall irradiation, with porcelain aorta. We decided to implant a 23-mm Edwards(®) SAPIEN(®) transcatheter aortic valve via a femoral route without using any contrast media. The implantation was successful after surgical approach of the femoral artery, transesophageal echocardiography guiding, and localization of native leaflets and coronary trunk with catheters. Immediate and one month post-interventional follow-up was favorable and echocardiography showed a good functioning of the aortic bioprosthesis. Although conventional angiography is the best way to visualize the good positioning of the valve before deployment, our case suggests that, in special situations, transfemoral implantation of an Edwards(®) SAPIEN(®) aortic bioprosthesis is feasible without any contrast injection. Copyright © 2012 Wiley Periodicals, Inc.

False Lumen Flow Patterns and their Relation with Morphological and Biomechanical Characteristics of Chronic Aortic Dissections. Computational Model Compared with Magnetic Resonance Imaging Measurements

PubMed Central

Segers, Patrick; Pineda, Victor; Cuellar, Hug; García-Dorado, David; Evangelista, Arturo

2017-01-01

Aortic wall stiffness, tear size and location and the presence of abdominal side branches arising from the false lumen (FL) are key properties potentially involved in FL enlargement in chronic aortic dissections (ADs). We hypothesize that temporal variations on FL flow patterns, as measured in a cross-section by phase-contrast magnetic resonance imaging (PC-MRI), could be used to infer integrated information on these features. In 33 patients with chronic descending AD, instantaneous flow profiles were quantified in the FL at diaphragm level by PC-MRI. We used a lumped-parameter model to assess the changes in flow profiles induced by wall stiffness, tear size/location, and the presence of abdominal side branches arising from the FL. Four characteristic FL flow patterns were identified in 31/33 patients (94%) based on the direction of flow in systole and diastole: BA = systolic biphasic flow and primarily diastolic antegrade flow (n = 6); BR = systolic biphasic flow and primarily diastolic retrograde flow (n = 14); MA = systolic monophasic flow and primarily diastolic antegrade flow (n = 9); MR = systolic monophasic flow and primarily diastolic retrograde flow (n = 2). In the computational model, the temporal variation of flow directions within the FL was highly dependent on the position of assessment along the aorta. FL flow patterns (especially at the level of the diaphragm) showed their characteristic patterns due to variations in the cumulative size and the spatial distribution of the communicating tears, and the incidence of visceral side branches originating from the FL. Changes in wall stiffness did not change the temporal variation of the flows whereas it importantly determined intraluminal pressures. FL flow patterns implicitly codify morphological information on key determinants of aortic expansion in ADs. This data might be taken into consideration in the imaging protocol to define the predictive value of FL flows. PMID:28125720

Aortic Wall Inflammation Predicts Abdominal Aortic Aneurysm Expansion, Rupture, and Need for Surgical Repair

PubMed Central

2017-01-01

Background: Ultrasmall superparamagnetic particles of iron oxide (USPIO) detect cellular inflammation on magnetic resonance imaging (MRI). In patients with abdominal aortic aneurysm, we assessed whether USPIO-enhanced MRI can predict aneurysm growth rates and clinical outcomes. Methods In a prospective multicenter open-label cohort study, 342 patients with abdominal aortic aneurysm (diameter ≥40 mm) were classified by the presence of USPIO enhancement and were monitored with serial ultrasound and clinical follow-up for ≥2 years. The primary end point was the composite of aneurysm rupture or repair. Results Participants (85% male, 73.1±7.2 years) had a baseline aneurysm diameter of 49.6±7.7 mm, and USPIO enhancement was identified in 146 (42.7%) participants, absent in 191 (55.8%), and indeterminant in 5 (1.5%). During follow-up (1005±280 days), 17 (5.0%) abdominal aortic aneurysm ruptures, 126 (36.8%) abdominal aortic aneurysm repairs, and 48 (14.0%) deaths occurred. Compared with those without uptake, patients with USPIO enhancement have increased rates of aneurysm expansion (3.1±2.5 versus 2.5±2.4 mm/year, P=0.0424), although this was not independent of current smoking habit (P=0.1993). Patients with USPIO enhancement had higher rates of aneurysm rupture or repair (47.3% versus 35.6%; 95% confidence intervals, 1.1–22.2; P=0.0308). This finding was similar for each component of rupture (6.8% versus 3.7%, P=0.1857) or repair (41.8% versus 32.5%, P=0.0782). USPIO enhancement was associated with reduced event-free survival for aneurysm rupture or repair (P=0.0275), all-cause mortality (P=0.0635), and aneurysm-related mortality (P=0.0590). Baseline abdominal aortic aneurysm diameter (P<0.0001) and current smoking habit (P=0.0446) also predicted the primary outcome, and the addition of USPIO enhancement to the multivariate model did not improve event prediction (c-statistic, 0.7935–0.7936). Conclusions USPIO-enhanced MRI is a novel approach to the identification of aortic wall cellular inflammation in patients with abdominal aortic aneurysms and predicts the rate of aneurysm growth and clinical outcome. However, it does not provide independent prediction of aneurysm expansion or clinical outcomes in a model incorporating known clinical risk factors. Clinical Trial Registration: URL: http://www.isrctn.com. Unique identifier: ISRCTN76413758. PMID:28720724

Ex vivo blood vessel bioreactor for analysis of the biodegradation of magnesium stent models with and without vessel wall integration.

PubMed

Wang, Juan; Liu, Lumei; Wu, Yifan; Maitz, Manfred F; Wang, Zhihong; Koo, Youngmi; Zhao, Ansha; Sankar, Jagannathan; Kong, Deling; Huang, Nan; Yun, Yeoheung

2017-03-01

Current in vitro models fail in predicting the degradation rate and mode of magnesium (Mg) stents in vivo. To overcome this, the microenvironment of the stent is simulated here in an ex vivo bioreactor with porcine aorta and circulating medium, and compared with standard static in vitro immersion and with in vivo rat aorta models. In ex vivo and in vivo conditions, pure Mg wires were exposed to the aortic lumen and inserted into the aortic wall to mimic early- and long-term implantation, respectively. Results showed that: 1) Degradation rates of Mg were similar for all the fluid diffusion conditions (in vitro static, aortic wall ex vivo and in vivo); however, Mg degradation under flow condition (i.e. in the lumen) in vivo was slower than ex vivo; 2) The corrosion mode in the samples can be mainly described as localized (in vitro), mixed localized and uniform (ex vivo), and uniform (in vivo); 3) Abundant degradation products (MgO/Mg(OH) 2 and Ca/P) with gas bubbles accumulated around the localized degradation regions ex vivo, but a uniform and thin degradation product layer was found in vivo. It is concluded that the ex vivo vascular bioreactor provides an improved test setting for magnesium degradation between static immersion and animal experiments and highlights its promising role in bridging degradation behavior and biological response for vascular stent research. Magnesium and its alloys are candidates for a new generation of biodegradable stent materials. However, the in vitro degradation of magnesium stents does not match the clinical degradation rates, corrupting the validity of conventional degradation tests. Here we report an ex vivo vascular bioreactor, which allows simulation of the microenvironment with and without blood vessel integration to study the biodegradation of magnesium implants in comparison with standard in vitro test conditions and with in vivo implantations. The bioreactor did simulate the corrosion of an intramural implant very well, but showed too high degradation for non-covered implants. It is concluded that this system is in between static incubation and animal experiments concerning the predictivity of the degradation. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

CFD modelling of abdominal aortic aneurysm on hemodynamic loads using a realistic geometry with CT.

PubMed

Soudah, Eduardo; Ng, E Y K; Loong, T H; Bordone, Maurizio; Pua, Uei; Narayanan, Sriram

2013-01-01

The objective of this study is to find a correlation between the abdominal aortic aneurysm (AAA) geometric parameters, wall stress shear (WSS), abdominal flow patterns, intraluminal thrombus (ILT), and AAA arterial wall rupture using computational fluid dynamics (CFD). Real AAA 3D models were created by three-dimensional (3D) reconstruction of in vivo acquired computed tomography (CT) images from 5 patients. Based on 3D AAA models, high quality volume meshes were created using an optimal tetrahedral aspect ratio for the whole domain. In order to quantify the WSS and the recirculation inside the AAA, a 3D CFD using finite elements analysis was used. The CFD computation was performed assuming that the arterial wall is rigid and the blood is considered a homogeneous Newtonian fluid with a density of 1050 kg/m(3) and a kinematic viscosity of 4 × 10(-3) Pa·s. Parallelization procedures were used in order to increase the performance of the CFD calculations. A relation between AAA geometric parameters (asymmetry index ( β ), saccular index ( γ ), deformation diameter ratio ( χ ), and tortuosity index ( ε )) and hemodynamic loads was observed, and it could be used as a potential predictor of AAA arterial wall rupture and potential ILT formation.

Angiotensin II Receptor Antagonism Reduces Transforming Growth Factor Beta and Smad Signaling in Thoracic Aortic Aneurysm

PubMed Central

Nataatmadja, Maria; West, Jennifer; Prabowo, Sulistiana; West, Malcolm

2013-01-01

ABSTRACT Background The expression of transforming growth factor beta (TGF-β) and Smad3 regulates extracellular matrix homeostasis and inflammation in aortic aneurysms. The expression of Smad3 depends on signaling by angiotensin II (AngII) receptor pathways through TGF-β receptor–dependent and –independent pathways. Methods To determine the expression of AngII type 1 (AT1R) and type 2 receptors (AT2R), TGF-β, and Smad3 in thoracic aortic aneurysms, we performed immunohistochemistry testing on tissue and cultured cells derived from subjects with Marfan syndrome (MFS) and bicuspid aortic valve (BAV) malformation and from normal aortas of subjects who were organ donors. Results MFS and BAV aneurysm tissue showed enhanced accumulation of TGF-β and Smad3 in vascular smooth muscle cells (VSMCs) and in inflammatory cells in the subintimal layer and tunica media. The normal aortic wall exhibited minimal TGF-β and Smad3 staining. Cultured VSMCs from MFS and BAV samples showed nuclear Smad3 and strong cytoplasmic TGF-β expression in the cytoplasmic vesicles. In control cells, Smad3 was located mainly in the cytoplasm, and weak cytoplasmic TGF-β was distributed with a pattern similar to that of the aneurysm-derived cells. Compared to normal aorta cells, AT1R and AT2R expression was increased in both aneurysm types. Treatment of cultured VSMCs with the AT1R antagonist losartan caused both reduced TGF-β vesicle localization and nuclear expression of Smad3. Conclusions Increased TGF-β and Smad3 expression in aneurysm tissue and cultured VSMCs is consistent with aberrant TGF-β expression and the activation of Smad3 signaling. Losartan-mediated reduction in TGF-β expression and the cytoplasmic localization of Smad3 support a role for AT1R antagonism in the inhibition of aneurysm progression. PMID:23532685

Combination Therapy with Atorvastatin and Amlodipine Suppresses Angiotensin II-Induced Aortic Aneurysm Formation

PubMed Central

Takahashi, Kikuyo; Matsumoto, Yasuharu; Do.e, Zhulanqiqige; Kanazawa, Masanori; Satoh, Kimio; Shimizu, Takuya; Sato, Akira; Fukumoto, Yoshihiro; Shimokawa, Hiroaki

2013-01-01

Background Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease. It is controversial whether statin and calcium channel blockers (CCBs) has an inhibitory effect on the expansion of AAA. Some studies reported that CCBs have an inhibitory effect on Rho-kinase activity. Rho-kinase plays an important role in the pathogenesis of various cardiovascular diseases. However, there is no study reporting of the association between Rho-kinase and human AAAs. Methods and Results Experimental AAA was induced in Apolipoprotein E-deficient (ApoE-/-) mice infused with angiotensin II (AngII) for 28 days. They were randomly divided into the following 5 groups; saline infusion alone (sham), AngII infusion alone, AngII infusion plus atorvastatin (10 mg/kg/day), AngII infusion plus amlodipine (1 mg/kg/day), and AngII infusion plus combination therapy with atorvastatin (10 mg/kg/day) and amlodipine (1 mg/kg/day). The combination therapy significantly suppressed AngII-induced increase in maximal aortic diameter as compared with sham, whereas each monotherapy had no inhibitory effects. The combination therapy significantly reduced AngII-induced apoptosis and elastin degradation at the AAA lesion, whereas each monotherapy did not. Moreover, Rho-kinase activity, as evaluated by the extent of phosphorylation of myosin-binding subunit (a substrate of Rho-kinase) and matrix metalloproteinase activity were significantly increased in the AngII-induced AAA lesion as compared with sham, both of which were again significantly suppressed by the combination therapy. In human aortic samples, immunohistochemistory revealed that the activity and expression of Rho-kinase was up-regulated in AAA lesion as compared with abdominal aorta from control subjects. Conclusions Rho-kinase is up-regulated in the aortic wall of human AAA. The combination therapy with amlodipine and Atorvastatin, but not each monotherapy, suppresses AngII-induced AAA formation in mice in vivo, for which Rho-kinase inhibition may be involved. PMID:23967318

Relationship Between Central and Peripheral Atherosclerosis and Left Ventricular Dysfunction in a Community Population

PubMed Central

Tsao, Connie W.; Gona, Philimon; Salton, Carol; Murabito, Joanne M.; Oyama, Noriko; Danias, Peter G.; O’Donnell, Christopher J.; Manning, Warren J.; Yeon, Susan B.

2011-01-01

We aimed to determine the relationships between resting left ventricular (LV) wall motion abnormalities (WMAs), aortic plaque, and PAD in a community cohort. 1726 Framingham Heart Study Offspring Cohort participants (806 males, 65±9 years) underwent cardiovascular magnetic resonance with quantification of aortic plaque volume and assessment of regional LV systolic function. Claudication, lower extremity revascularization, and ankle-brachial index (ABI) were recorded at Examination 7. WMAs were associated with greater aortic plaque burden, decreased ABI, and claudication in age- and sex-adjusted analyses (all p<0.001), which were not significant after adjustment for cardiovascular risk factors. In age- and sex-adjusted analyses, both the presence (p<0.001) and volume of aortic plaque were associated with decreased ABI (p<0.001). After multivariable adjustment, ABI≤0.9 or prior revascularization was associated with a three-fold odds of aortic plaque (p=0.0083). Plaque volume significantly increased with decreasing ABI in multivariable-adjusted analyses (p<0.0001). In this free-living population, associations of WMAs with aortic plaque burden and clinical measures of PAD were attenuated after adjustment for coronary heart disease risk factors. Aortic plaque volume and ABI remained strongly negatively correlated after multivariable adjustment. Our findings suggest that the association between coronary heart disease and non-coronary atherosclerosis is explained by cardiovascular risk factors. Aortic atherosclerosis and PAD remain strongly associated after multivariable adjustment suggesting shared mechanisms beyond those captured by traditional risk factors. PMID:21708875

Association between osteopontin and human abdominal aortic aneurysm.

PubMed

Golledge, Jonathan; Muller, Juanita; Shephard, Neil; Clancy, Paula; Smallwood, Linda; Moran, Corey; Dear, Anthony E; Palmer, Lyle J; Norman, Paul E

2007-03-01

In vitro and animal studies have implicated osteopontin (OPN) in the pathogenesis of aortic aneurysm. The relationship between serum concentration of OPN and variants of the OPN gene with human abdominal aortic aneurysm (AAA) was investigated. OPN genotypes were examined in 4227 subjects in which aortic diameter and clinical risk factors were measured. Serum OPN was measured by ELISA in two cohorts of 665 subjects. The concentration of serum OPN was independently associated with the presence of AAA. Odds ratios (and 95% confidence intervals) for upper compared with lower OPN tertiles in predicting presence of AAA were 2.23 (1.29 to 3.85, P=0.004) for the population cohort and 4.08 (1.67 to 10.00, P=0.002) for the referral cohort after adjusting for other risk factors. In 198 patients with complete follow-up of aortic diameter at 3 years, initial serum OPN predicted AAA growth after adjustment for other risk factors (standardized coefficient 0.24, P=0.001). The concentration of OPN in the aortic wall was greater in patients with small AAAs (30 to 50 mm) than those with aortic occlusive disease alone. There was no association between five single nucleotide polymorphisms or haplotypes of the OPN gene and aortic diameter or AAA expansion. Serum and tissue concentrations of OPN are associated with human AAA. We found no relationship between variation of the OPN gene and AAA. OPN may be a useful biomarker for AAA presence and growth.

Race-Specific Associations of Myeloperoxidase with Atherosclerosis in a Population-Based Sample: The Dallas Heart Study

PubMed Central

Chen, Lu; Rohatgi, Anand; Ayers, Colby R.; Das, Sandeep R.; Khera, Amit; Berry, Jarett D.; McGuire, Darren K.; de Lemos, James A.

2011-01-01

Objective Myeloperoxidase (MPO) is a leukocyte-derived enzyme that appears to be directly involved in atherosclerosis development. We evaluated the association of circulating MPO with coronary and aortic atherosclerosis in a large, multiethnic population. Methods and Results Plasma levels of MPO were measured in 3294 subjects participating in the Dallas Heart Study, a probability-based population sample. Coronary artery calcification (CAC) was measured by EBCT, and abdominal aorta plaque prevalence (AP) and burden (APB), as well as abdominal aorta wall thickness (AWT) were determined by MRI. Associations between MPO and atherosclerosis phenotypes were assessed in multivariable analyses adjusting for traditional atherosclerosis risk factors. MPO levels in the 4th compared with 1st quartile independently associated with prevalent AP (OR 1.41, 95% CI 1.08–1.84), APB (beta coefficient 0.23, p=0.02), and AWT (beta coefficient 0.04, p=0.03), but not with prevalent CAC (OR 0.84, 95% CI 0.61–1.17). MPO remained associated with aortic atherosclerosis phenotypes but not coronary calcification after adjustment for other inflammatory biomarkers. A significant interaction was observed between race/ethnicity, MPO and AP (pinteraction=0.038), such that MPO levels in the 4th vs 1st quartile associated with prevalent AP in African Americans, (OR 1.81, 95% CI 1.23–2.65) but not in White or Hispanic participants (OR 0.99, 95% CI 0.68–1.44). Conclusion Higher levels of MPO associated with aortic but not coronary atherosclerosis, with significant associations limited to African American participants. These findings suggest that MPO might be a novel risk factor contributing to racial disparities in peripheral vascular disease. PMID:21917261

Impact of different aortic valve calcification patterns on the outcome of transcatheter aortic valve implantation: A finite element study.

PubMed

Sturla, Francesco; Ronzoni, Mattia; Vitali, Mattia; Dimasi, Annalisa; Vismara, Riccardo; Preston-Maher, Georgia; Burriesci, Gaetano; Votta, Emiliano; Redaelli, Alberto

2016-08-16

Transcatheter aortic valve implantation (TAVI) can treat symptomatic patients with calcific aortic stenosis. However, the severity and distribution of the calcification of valve leaflets can impair the TAVI efficacy. Here we tackle this issue from a biomechanical standpoint, by finite element simulation of a widely adopted balloon-expandable TAVI in three models representing the aortic root with different scenarios of calcific aortic stenosis. We developed a modeling approach realistically accounting for aortic root pressurization and complex anatomy, detailed calcification patterns, and for the actual stent deployment through balloon-expansion. Numerical results highlighted the dependency on the specific calcification pattern of the "dog-boning" of the stent. Also, local stent distortions were associated with leaflet calcifications, and led to localized gaps between the TAVI stent and the aortic tissues, with potential implications in terms of paravalvular leakage. High stresses were found on calcium deposits, which may be a risk factor for stroke; their magnitude and the extent of the affected regions substantially increased for the case of an "arc-shaped" calcification, running from commissure to commissure. Moreover, high stresses due to the interaction between the aortic wall and the leaflet calcifications were computed in the annular region, suggesting an increased risk for annular damage. Our analyses suggest a relation between the alteration of the stresses in the native anatomical components and prosthetic implant with the presence and distribution of relevant calcifications. This alteration is dependent on the patient-specific features of the calcific aortic stenosis and may be a relevant indicator of suboptimal TAVI results. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Matrix metalloproteinases. Their role in degenerative chronic diseases of abdominal aorta.

PubMed

Palombo, D; Maione, M; Cifiello, B I; Udini, M; Maggio, D; Lupo, M

1999-04-01

The main chronic degenerative diseases of the abdominal aorta, namely aneurysmatic and steno-obstructive pathologies, have a common denominator: atherosclerosis. Both pathologies are characterised by the destruction of the structural integrity of the extracellular protein matrix (ME). A number of studies have shown the presence and involvement of a group of enzymes with proteolytic activity towards one or more ME components, the matrix metalloproteinases (MMPs), in the pathogenesis of aneurysms of the abdominal aorta. Other authors have underlined the role of MMPs in the proliferation and migration process of smooth muscle cells into the intima in the pathogenesis of atheromasic plaque. The aim of this study was to evaluate the possible role of these enzymes in the pathogenesis of chronic degenerative diseases of the aorta. Fragments of aortic wall were removed from patients undergoing elective aortic surgery for aneurysms (14 patients) or aortic steno-obstruction (4 patients). The samples obtained were treated appropriately and then subject to immunohistochemical analysis. The preparations were incubated with specific anti-MMP antibodies and were also incubated with substrate and chromogen, forming a pigmented precipitate on the site of the antigen, before being observed using an optic microscopic at an enlargement of 250x. Nuclear positivity linked to the presence of the antigen testified the validity of staining. Lastly, the MMP INDEX, or in other words the number of positive cells out of 100, was stained in the adventitia and in the tunica media in each preparation. MMPs were divided into three main groups: interstitial collagenase (MMP1) which degrade type I and III native collagen; gelatinases (MMP9, MMP2) which act on elastin and type IV collagen; stromelysins (MMP3) with specific proteolytic action towards proteoglycans, fibronectin and laminine. In our experience, those preparations obtained from aorta affected by steno-obstructive pathologies (4 patients) revealed the presence of MMPs with a preferential localisation on the intimal side of the tunica media. In particular, the increased activity of gelatinases MMP9 in atherosclerotic aorta might be responsible for destroying the internal elastic lamina and fostering the proliferation and migration of smooth muscle cells and the formation of atheromasic plaque. On the other hand, preparations obtained from aneurysmatic aorta (14 patients) showed an opposite situation with a preferential localisation within the adventitia and on the adventitial side of the media. Above all, the loss of elastin represents an essential stage in the formation of aortic aneurysms. This study concords with numerous authors who have demonstrated the involvement of proteinase MMPs in the development of aortic aneurysms and their possible role in the pathogenesis of atheromasic plaque. The different origin of these enzymes (inflammatory cells and macrophages or endothelial cells) may be the result of different pathogenetic mechanisms. Although they present different pathogenetic features, aortic aneurysms and steno-obstructions have a common denominator in atherosclerosis. The mechanisms responsible for their evolution towards one or other form are not known. The different expression of MMPs in the context of the aortic wall represents a field for future research.

Strong correlation between early stage atherosclerosis and electromechanical coupling of aorta

NASA Astrophysics Data System (ADS)

Liu, X. Y.; Yan, F.; Niu, L. L.; Chen, Q. N.; Zheng, H. R.; Li, J. Y.

2016-03-01

Atherosclerosis is the underlying cause of cardiovascular diseases that are responsible for many deaths in the world, and the early diagnosis of atherosclerosis is highly desirable. The existing imaging methods, however, are not capable of detecting the early stage of atherosclerosis development due to their limited spatial resolution. Using piezoresponse force microscopy (PFM), we show that the piezoelectric response of an aortic wall increases as atherosclerosis advances, while the stiffness of the aorta shows a less evident correlation with atherosclerosis. Furthermore, we show that there is strong correlation between the coercive electric field necessary to switch the polarity of the artery and the development of atherosclerosis. Thus by measuring the electromechanical coupling of the aortic wall, it is possible to probe atherosclerosis at the early stage of its development, not only improving the spatial resolution by orders of magnitude, but also providing comprehensive quantitative information on the biomechanical properties of the artery.

MDCT distinguishing features of focal aortic projections (FAP) in acute clinical settings.

PubMed

Valente, Tullio; Rossi, Giovanni; Lassandro, Francesco; Rea, Gaetano; Marino, Maurizio; Urciuolo, Salvatore; Tortora, Giovanni; Muto, Maurizio

2015-01-01

Focal aortic projections (FAP) are protrusion images of the contrast medium (focal contour irregularity, breaks in the intimal contour, outward lumen bulging or localized blood-filled outpouching) projecting beyond the aortic lumen in the aortic wall and are commonly seen on multidetector computed tomography (MDCT) scans of the chest and abdomen. FAP include several common and uncommon etiologies, which can be demonstrated both in the native aorta, mainly in acute aortic syndromes, and in the post-surgical aorta or after endovascular therapy. They are also found in some types of post-traumatic injuries and in impending rupture of the aneurysms. The expanding, routine use of millimetric or submillimetric collimation of current state-of-the-art MDCT scanners (16 rows and higher) all the time allows the identification and characterization of these small ulcer-like lesions or irregularities in the entire aorta, as either an incidental or expected finding, and provides detailed three-dimensional pictures of these pathologic findings. In this pictorial review, we illustrate the possible significance of FAP and the discriminating MDCT features that help to distinguish among different types of aortic protrusions and their possible evolution. Awareness of some related and distinctive radiologic features in FAP may improve our understanding of aortic diseases, provide further insight into the pathophysiology and natural history, and guide the appropriate management of these lesions.

[Usefullness of transesophageal echocardiography in early detection of coronary spasm].

PubMed

Sagara, M; Haraguchi, M; Hamu, Y; Isowaki, S; Yoshimura, N

1996-04-01

Intraoperative transesophageal echocardiography (TEE) was performed on a 62-year-old man who underwent abdominal aortic replacement for abdominal aortic aneurysm under general anesthesia combined with epidural anesthesia. Coronary artery spasm occurred after unexpected massive hemorrhage, and TEE showed hypokinesis in the posterior-inferior left ventricular wall. The changes in TEE preceded the ST elevation in the ECG. Bolus infusion of isosorbide dinitrate and continuous infusion of nitroglycerin alleviated these changes. TEE enabled us to detect and evaluate coronary spasm before the appearance of ST changes in ECG.

Pathologic aneurysmal dilation of the ascending aorta and dilation of the main pulmonary artery in patients with Kabuki syndrome: valve-sparing aortic root replacement.

PubMed

Dyamenahalli, Umesh; Abraham, Boban; Fontenot, Eudice; Prasad, Vinay; Imamura, Michiaki

2007-01-01

We report the aneurysmal dilation of the ascending aorta and the main pulmonary artery in 2 children with Kabuki syndrome. In 1 patient, there was progressive aneurysmal dilation of the ascending aorta necessitating aortoplasty. Histologic examination of the resected aorta revealed disrupted and fragmented elastic fibers in the medial layer, along with mucinous degeneration of the aortic wall. This is the first recognition and report of these findings as part of the Kabuki syndrome.

Feasibility of wall stress analysis of abdominal aortic aneurysms using three-dimensional ultrasound.

PubMed

Kok, Annette M; Nguyen, V Lai; Speelman, Lambert; Brands, Peter J; Schurink, Geert-Willem H; van de Vosse, Frans N; Lopata, Richard G P

2015-05-01

Abdominal aortic aneurysms (AAAs) are local dilations that can lead to a fatal hemorrhage when ruptured. Wall stress analysis of AAAs is a novel tool that has proven high potential to improve risk stratification. Currently, wall stress analysis of AAAs is based on computed tomography (CT) and magnetic resonance imaging; however, three-dimensional (3D) ultrasound (US) has great advantages over CT and magnetic resonance imaging in terms of costs, speed, and lack of radiation. In this study, the feasibility of 3D US as input for wall stress analysis is investigated. Second, 3D US-based wall stress analysis was compared with CT-based results. The 3D US and CT data were acquired in 12 patients (diameter, 35-90 mm). US data were segmented manually and compared with automatically acquired CT geometries by calculating the similarity index and Hausdorff distance. Wall stresses were simulated at P = 140 mm Hg and compared between both modalities. The similarity index of US vs CT was 0.75 to 0.91 (n = 12), with a median Hausdorff distance ranging from 4.8 to 13.9 mm, with the higher values found at the proximal and distal sides of the AAA. Wall stresses were in accordance with literature, and a good agreement was found between US- and CT-based median stresses and interquartile stresses, which was confirmed by Bland-Altman and regression analysis (n = 8). Wall stresses based on US were typically higher (+23%), caused by geometric irregularities due to the registration of several 3D volumes and manual segmentation. In future work, an automated US registration and segmentation approach is the essential point of improvement before pursuing large-scale patient studies. This study is a first step toward US-based wall stress analysis, which would be the modality of choice to monitor wall stress development over time because no ionizing radiation and contrast material are involved. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Hemodynamics of physiological blood flow in the aorta with nonlinear anisotropic heart valve

NASA Astrophysics Data System (ADS)

Sotiropoulos, Fotis; Gilmanov, Anvar; Stolarski, Henryk

2016-11-01

The hemodynamic blood flow in cardiovascular system is one of the most important factor, which causing several vascular diseases. We developed a new Curvilinear Immersed Boundary - Finite Element - Fluid Structure Interaction (CURVIB-FE-FSI) method to analyze hemodynamic of pulsatile blood flow in a real aorta with nonlinear anisotropic aortic valve at physiological conditions. Hyperelastic material model, which is more realistic for describing heart valve have been incorporated in the CURVIB-FE-FSI code to simulate interaction of aortic heart valve with pulsatile blood flow. Comparative studies of hemodynamics for linear and nonlinear models of heart valve show drastic differences in blood flow patterns and hence differences of stresses causing impact at leaflets and aortic wall. This work is supported by the Lillehei Heart Institute at the University of Minnesota.

INCLUDING AORTIC VALVE MORPHOLOGY IN COMPUTATIONAL FLUID DYNAMICS SIMULATIONS: INITIAL FINDINGS AND APPLICATION TO AORTIC COARCTATION

PubMed Central

Wendell, David C.; Samyn, Margaret M.; Cava, Joseph R.; Ellwein, Laura M.; Krolikowski, Mary M.; Gandy, Kimberly L.; Pelech, Andrew N.; Shadden, Shawn C.; LaDisa, John F.

2012-01-01

Computational fluid dynamics (CFD) simulations quantifying thoracic aortic flow patterns have not included disturbances from the aortic valve (AoV). 80% of patients with aortic coarctation (CoA) have a bicuspid aortic valve (BAV) which may cause adverse flow patterns contributing to morbidity. Our objectives were to develop a method to account for the AoV in CFD simulations, and quantify its impact on local hemodynamics. The method developed facilitates segmentation of the AoV, spatiotemporal interpolation of segments, and anatomic positioning of segments at the CFD model inlet. The AoV was included in CFD model examples of a normal (tricuspid AoV) and a post-surgical CoA patient (BAV). Velocity, turbulent kinetic energy (TKE), time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) results were compared to equivalent simulations using a plug inlet profile. The plug inlet greatly underestimated TKE for both examples. TAWSS differences extended throughout the thoracic aorta for the CoA BAV, but were limited to the arch for the normal example. OSI differences existed mainly in the ascending aorta for both cases. The impact of AoV can now be included with CFD simulations to identify regions of deleterious hemodynamics thereby advancing simulations of the thoracic aorta one step closer to reality. PMID:22917990

Biomechanical Indices for Rupture Risk Estimation in Abdominal Aortic Aneurysms.

PubMed

Leemans, Eva L; Willems, Tineke P; van der Laan, Maarten J; Slump, Cornelis H; Zeebregts, Clark J

2017-04-01

To review the use of biomechanical indices for the estimation of abdominal aortic aneurysm (AAA) rupture risk, emphasizing their potential use in a clinical setting. A search of the PubMed, Embase, Scopus, and Compendex databases was made up to June 2015 to identify articles involving biomechanical analysis of AAA rupture risk. Outcome variables [aneurysm diameter, peak wall stress (PWS), peak wall shear stress (PWSS), wall strain, peak wall rupture index (PWRI), and wall stiffness] were compared for asymptomatic intact AAAs vs symptomatic or ruptured AAAs. For quantitative analysis of the pooled data, a random effects model was used to calculate the standard mean differences (SMDs) with the 95% confidence interval (CI) for the biomechanical indices. The initial database searches yielded 1894 independent articles of which 19 were included in the analysis. The PWS was significantly higher in the symptomatic/ruptured group, with a SMD of 1.11 (95% CI 0.93 to 1.26, p<0.001). Likewise, the PWRI was significantly higher in the ruptured or symptomatic group, with a SMD of 1.15 (95% CI 0.30 to 2.01, p=0.008). After adjustment for the aneurysm diameter, the PWS remained higher in the ruptured or symptomatic group, with a SMD of 0.85 (95% CI 0.46 to 1.23, p<0.001). Less is known of the wall shear stress and wall strain indices, as too few studies were available for analysis. Biomechanical indices are a promising tool in the assessment of AAA rupture risk as they incorporate several factors, including geometry, tissue properties, and patient-specific risk factors. However, clinical implementation of biomechanical AAA assessment remains a challenge owing to a lack of standardization.

Type A Aortic Dissection Presenting with Inferior ST-Elevation Myocardial Infarction.

PubMed

Wu, Bao-Tzung; Li, Chun-Yi; Chen, Ying-Tsung

2014-05-01

Type A aortic dissection with concurrent ST-elevation myocardial infarction (STEMI) is relatively rare. However, it can be potentially fatal and easily misdiagnosed as STEMI alone. Misdiagnosis will lead to inappropriate administration of anticoagulant and thrombolytic therapy and delayed surgical repair of the aorta. In patients with STEMI, short reperfusion time is associated with improved survival, and minimizing the door-to-balloon time is the goal of therapy worldwide. However, signs critical for differential diagnosis may be overlooked in the rush to primary percutaneous coronary intervention. When a patient is encountered who presents with chest pain and ST elevation on electrocardiogram, STEMI should not be the only diagnosis considered. By using bedside available information, detailed history taking and focused physical examination, it is possible to avoid a mistaken diagnosis. Here we report a case of Stanford type A aortic dissection with STEMI that was initially misdiagnosed as sole acute inferior wall myocardial infarction. Patient mortality may have resulted from delayed diagnosis and surgical treatment. Acute myocardial infarction; Aortic dissection.

Immersed boundary peridynamics (IB/PD) method to simulate aortic dissection

NASA Astrophysics Data System (ADS)

Bhalla, Amneet Pal Singh; Griffith, Boyce

2016-11-01

Aortic dissection occurs when an intimal tear in the aortic wall propagates into the media to form a false lumen within the vessel wall. Rupture of the false lumen and collapse of the true lumen both carry a high risk of morbidity and mortality. Surgical treatment consists of either replacement of a portion of the aorta, or stent implantation to cover the affected segment. Both approaches carry significant risks: open surgical intervention is highly invasive, whereas stents can be challenging to implant and offer unclear long-term patient outcomes. It is also difficult to time optimally the intervention to ensure that the benefits of treatment outweigh its risks. In this work we develop innovative fluid-structure interaction (FSI) model combining elements from immersed boundary (IB) and peridynamics (PD) methods to simulate tears in membranes. The new approach is termed as IB/PD method. We use non-ordinary state based PD to represent material hyperelasticity. Several test problems are taken to validate peridynamics approach to model structural dynamics, with and without accounting for failure in the structures. FSI simulations using IB/PD method are compared with immersed finite element method (IB/FE) to validate the new hybrid approach. NIH Award R01HL117163 NSF Award ACI 1450327.

Assessment of Hemodynamic Conditions in the Aorta Following Root Replacement with Composite Valve-Conduit Graft.

PubMed

Cheng, Zhuo; Kidher, Emaddin; Jarral, Omar A; O'Regan, Declan P; Wood, Nigel B; Athanasiou, Thanos; Xu, Xiao Yun

2016-05-01

This paper presents the analysis of detailed hemodynamics in the aortas of four patients following replacement with a composite bio-prosthetic valve-conduit. Magnetic resonance image-based computational models were set up for each patient with boundary conditions comprising subject-specific three-dimensional inflow velocity profiles at the aortic root and central pressure waveform at the model outlet. Two normal subjects were also included for comparison. The purpose of the study was to investigate the effects of the valve-conduit on flow in the proximal and distal aorta. The results suggested that following the composite valve-conduit implantation, the vortical flow structure and hemodynamic parameters in the aorta were altered, with slightly reduced helical flow index, elevated wall shear stress and higher non-uniformity in wall shear compared to normal aortas. Inter-individual analysis revealed different hemodynamic conditions among the patients depending on the conduit configuration in the ascending aorta, which is a key factor in determining post-operative aortic flow. Introducing a natural curvature in the conduit to create a smooth transition between the conduit and native aorta may help prevent the occurrence of retrograde and recirculating flow in the aortic arch, which is particularly important when a large portion or the entire ascending aorta needs to be replaced.

Haemodynamic imaging of thoracic stent-grafts by computational fluid dynamics (CFD): presentation of a patient-specific method combining magnetic resonance imaging and numerical simulations.

PubMed

Midulla, Marco; Moreno, Ramiro; Baali, Adil; Chau, Ming; Negre-Salvayre, Anne; Nicoud, Franck; Pruvo, Jean-Pierre; Haulon, Stephan; Rousseau, Hervé

2012-10-01

In the last decade, there was been increasing interest in finding imaging techniques able to provide a functional vascular imaging of the thoracic aorta. The purpose of this paper is to present an imaging method combining magnetic resonance imaging (MRI) and computational fluid dynamics (CFD) to obtain a patient-specific haemodynamic analysis of patients treated by thoracic endovascular aortic repair (TEVAR). MRI was used to obtain boundary conditions. MR angiography (MRA) was followed by cardiac-gated cine sequences which covered the whole thoracic aorta. Phase contrast imaging provided the inlet and outlet profiles. A CFD mesh generator was used to model the arterial morphology, and wall movements were imposed according to the cine imaging. CFD runs were processed using the finite volume (FV) method assuming blood as a homogeneous Newtonian fluid. Twenty patients (14 men; mean age 62.2 years) with different aortic lesions were evaluated. Four-dimensional mapping of velocity and wall shear stress were obtained, depicting different patterns of flow (laminar, turbulent, stenosis-like) and local alterations of parietal stress in-stent and along the native aorta. A computational method using a combined approach with MRI appears feasible and seems promising to provide detailed functional analysis of thoracic aorta after stent-graft implantation. • Functional vascular imaging of the thoracic aorta offers new diagnostic opportunities • CFD can model vascular haemodynamics for clinical aortic problems • Combining CFD with MRI offers patient specific method of aortic analysis • Haemodynamic analysis of stent-grafts could improve clinical management and follow-up.

Decorin and biglycan retain LDL in disease-prone valvular and aortic subendothelial intimal matrix

PubMed Central

Neufeld, Edward B.; Zadrozny, Leah M.; Phillips, Darci; Aponte, Angel; Yu, Zu-Xi; Balaban, Robert S.

2014-01-01

Objective Subendothelial LDL retention by intimal matrix proteoglycans is an initial step in atherosclerosis and calcific aortic valve disease. Herein, we identify decorin and biglycan as the proteoglycans that preferentially retain LDL in intimal matrix at disease-prone sites in normal valve and vessel wall. Methods The porcine aortic valve and renal artery ostial diverter, initiation sites of calcific valve disease and renal atherosclerosis, respectively, from normal non-diseased animals were used as models in these studies. Results Fluorescent human LDL was selectively retained on the lesion-prone collagen/proteoglycan-enriched aortic surface of the valve, where the elastic lamina is depleted, as previously observed in lesion-prone sites in the renal ostium. iTRAQ mass spectrometry of valve and diverter protein extracts identified decorin and biglycan as the major subendothelial intimal matrix proteoglycans electrostatically retained on human LDL affinity columns. Decorin levels correlated with LDL binding in lesion-prone sites in both tissues. Collagen binding to LDL was shown to be proteoglycan-mediated. All known basement membrane proteoglycans bound LDL suggesting they may modulate LDL uptake into the subendothelial matrix. The association of purified decorin with human LDL in an in vitro microassay was blocked by serum albumin and heparin suggesting anti-atherogenic roles for these proteins in vivo. Conclusions LDL electrostatic interactions with decorin and biglycan in the valve leaflets and vascular wall is a major source of LDL retention. The complementary electrostatic sites on LDL or these proteoglycans may provide a novel therapeutic target for preventing one of the earliest events in these cardiovascular diseases. PMID:24529131

Association of aortic wall thickness on contrast-enhanced chest CT with major cerebro-cardiac events.

PubMed

Tresoldi, Silvia; Di Leo, Giovanni; Zoffoli, Elena; Munari, Alice; Primolevo, Alessandra; Cornalba, Gianpaolo; Sardanelli, Francesco

2014-11-01

There is a significant association between aortic atherosclerosis and previous major cardiovascular events. Particularly, thoracic aortic atherosclerosis is closely related to the degree of coronary and carotid artery disease. Thus, there is a rationale for screening the thoracic aorta in patients who undergo a chest computed tomography (CT) for any clinical question, in order to detect patients at increased risk of cerebro-cardiovascular (CCV) events. To estimate the association between either thoracic aortic wall thickness (AWT) or aortic total calcium score (ATCS) and CCV events. One hundred and forty-eight non-cardiac patients (78 men; 67 ± 12 years) underwent chest contrast-enhanced multidetector CT (MDCT). The AWT was measured at the level of the left atrium (AWTref) and at the maximum AWT (AWTmax). Correlation with clinical CCV patients' history was estimated. The value of AWTmax and of a semi-quantitative ATCS as a marker for CCV events was assessed using receiver-operating characteristic curve (ROC) analysis and multivariate regression analysis. Out of 148 patients, 59% reported sedentary lifestyle, 44% hypertension, 32% smoking, 23% hypercholesterolemia, 13% family history of cardiac disease, 12% diabetes, and 10% BMI ≥ 30 kg/m(2); 9% reported myocardial infarction, 8% aortic aneurism, 8% myocardial revascularization, and 2% ischemic stroke. Twenty-six percent of patients had a medium-to-high ATCS. Both AWTmax and AWTref correlated with hypertension and age (P < 0.002). At the ROC analysis, a 4.8 mm threshold was associated to a 90% specificity and an odds ratio of 6.3 (AUC = 0.735). Assuming as threshold the AWTmax median value (4.3 mm) of patients who suffered from at least one CCV event in their history, a negative predictive value of 90%, a RR of 3.6 and an OR of 6.3 were found. At the multivariate regression analysis, AWTmax was the only independent variable associated to the frequency of CCV events. Patients with increased thoracic AWTmax on chest MDCT could be considered at risk for CCV disease. © The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Measurements of Intra‐Aortic Balloon Wall Movement During Inflation and Deflation: Effects of Angulation

PubMed Central

Bruti, Gianpaolo; Kolyva, Christina; Pepper, John R.

2015-01-01

Abstract The intra‐aortic balloon pump (IABP) is a ventricular assist device that is used with a broad range of pre‐, intra‐, and postoperative patients undergoing cardiac surgery. Although the clinical efficacy of the IABP is well documented, the question of reduced efficacy when patients are nursed in the semi‐recumbent position remains outstanding. The aim of the present work is therefore to investigate the underlying mechanics responsible for the loss of IABP performance when operated at an angle to the horizontal. Simultaneous recordings of balloon wall movement, providing an estimate of its diameter (D), and fluid pressure were taken at three sites along the intra‐aortic balloon (IAB) at 0 and 45°. Flow rate, used for the calculation of displaced volume, was also recorded distal to the tip of the balloon. An in vitro experimental setup was used, featuring physiological impedances on either side of the IAB ends. IAB inflation at an angle of 45° showed that D increases at the tip of the IAB first, presenting a resistance to the flow displaced away from the tip of the balloon. The duration of inflation decreased by 15.5%, the inflation pressure pulse decreased by 9.6%, and volume decreased by 2.5%. Similarly, changing the position of the balloon from 0 to 45°, the balloon deflation became slower by 35%, deflation pressure pulse decreased by 14.7%, and volume suctioned was decreased by 15.2%. IAB wall movement showed that operating at 45° results in slower deflation compared with 0°. Slow wall movement, and changes in inflation and deflation onsets, result in a decreased volume displacement and pressure pulse generation. Operating the balloon at an angle to the horizontal, which is the preferred nursing position in intensive care units, results in reduced IAB inflation and deflation performance, possibly compromising its clinical benefits. PMID:25959284

Histopathology of aortic complications in bicuspid aortic valve versus Marfan syndrome: relevance for therapy?

PubMed

Grewal, Nimrat; Franken, Romy; Mulder, Barbara J M; Goumans, Marie-José; Lindeman, Johannes H N; Jongbloed, Monique R M; DeRuiter, Marco C; Klautz, Robert J M; Bogers, Ad J J C; Poelmann, Robert E; Groot, Adriana C Gittenberger-de

2016-05-01

Patients with bicuspid aortic valve (BAV) and patients with Marfan syndrome (MFS) are more prone to develop aortic dilation and dissection compared to persons with a tricuspid aortic valve (TAV). To elucidate potential common and distinct pathways of clinical relevance, we compared the histopathological substrates of aortopathy. Ascending aortic wall biopsies were divided in five groups: BAV (n = 36) and TAV (n = 23) without and with dilation and non-dilated MFS (n = 8). General histologic features, apoptosis, the expression of markers for vascular smooth muscle cell (VSMC) maturation, markers predictive for ascending aortic dilation in BAV, and expression of fibrillin-1 were investigated. Both MFS and BAV showed an altered distribution and decreased fibrillin-1 expression in the aorta and a significantly lower level of differentiated VSMC markers. Interestingly, markers predictive for aortic dilation in BAV were not expressed in the MFS aorta. The aorta in MFS was similar to the aorta in dilated TAV with regard to the presence of medial degeneration and apoptosis, while other markers for degeneration and aging like inflammation and progerin expression were low in MFS, comparable to BAV. Both MFS and BAV aortas have immature VSMCs, while MFS and TAV patients have a similar increased rate of medial degeneration. However, the mechanism leading to apoptosis is expected to be different, being fibrillin-1 mutation induced increased angiotensin-receptor-pathway signaling in MFS and cardiovascular aging and increased progerin in TAV. Our findings could explain why angiotensin inhibition is successful in MFS and less effective in TAV and BAV patients.

Relationship between central and peripheral atherosclerosis and left ventricular dysfunction in a community population.

PubMed

Tsao, Connie W; Gona, Philimon; Salton, Carol; Murabito, Joanne M; Oyama, Noriko; Danias, Peter G; O'Donnell, Christopher J; Manning, Warren J; Yeon, Susan B

2011-08-01

We aimed to determine the relationships between resting left ventricular (LV) wall motion abnormalities (WMAs), aortic plaque, and peripheral artery disease (PAD) in a community cohort. A total of 1726 Framingham Heart Study Offspring Cohort participants (806 males, 65 ± 9 years) underwent cardiovascular magnetic resonance with quantification of aortic plaque volume and assessment of regional left ventricular systolic function. Claudication, lower extremity revascularization, and ankle-brachial index (ABI) were recorded at the most contemporaneous examination visit. WMAs were associated with greater aortic plaque burden, decreased ABI, and claudication in age- and sex-adjusted analyses (all p < 0.001), which were not significant after adjustment for cardiovascular risk factors. In age- and sex-adjusted analyses, both the presence (p < 0.001) and volume of aortic plaque were associated with decreased ABI (p < 0.001). After multivariable adjustment, an ABI ≤ 0.9 or prior revascularization was associated with a threefold odds of aortic plaque (p = 0.0083). Plaque volume significantly increased with decreasing ABI in multivariable-adjusted analyses (p < 0.0001). In this free-living population, associations of WMAs with aortic plaque burden and clinical measures of PAD were attenuated after adjustment for coronary heart disease risk factors. Aortic plaque volume and ABI remained strongly negatively correlated after multivariable adjustment. Our findings suggest that the association between coronary heart disease and non-coronary atherosclerosis is explained by cardiovascular risk factors. Aortic atherosclerosis and PAD remain strongly associated after multivariable adjustment, suggesting shared mechanisms beyond those captured by traditional risk factors.

Bicuspid aortic valve hemodynamics: a fluid-structure interaction study

NASA Astrophysics Data System (ADS)

Chandra, Santanu; Seaman, Clara; Sucosky, Philippe

2011-11-01

The bicuspid aortic valve (BAV) is a congenital defect in which the aortic valve forms with two leaflets instead of three. While calcific aortic valve disease (CAVD) also develops in the normal tricuspid aortic valve (TAV), its progression in the BAV is more rapid. Although studies have suggested a mechano-potential root for the disease, the native BAV hemodynamics remains largely unknown. This study aimed at characterizing BAV hemodynamics and quantifying the degree of wall-shear stress (WSS) abnormality on BAV leaflets. Fluid-structure interaction models validated with particle-image velocimetry were designed to predict the flow and leaflet dynamics in idealized TAV and BAV anatomies. Valvular function was quantified in terms of the effective orifice area. The regional leaflet WSS was characterized in terms of oscillatory shear index, temporal shear magnitude and temporal shear gradient. The predictions indicate the intrinsic degree of stenosis of the BAV anatomy, reveal drastic differences in shear stress magnitude and pulsatility on BAV and TAV leaflets and confirm the side- and site-specificity of the leaflet WSS. Given the ability of abnormal fluid shear stress to trigger valvular inflammation, these results support the existence of a mechano-etiology of CAVD in the BAV.

Fluid Dynamics of Coarctation of the Aorta and Effect of Bicuspid Aortic Valve

PubMed Central

Keshavarz-Motamed, Zahra; Garcia, Julio; Kadem, Lyes

2013-01-01

Up to 80% of patients with coarctation of the aorta (COA) have a bicuspid aortic valve (BAV). Patients with COA and BAV have elevated risks of aortic complications despite successful surgical repair. The development of such complications involves the interplay between the mechanical forces applied on the artery and the biological processes occurring at the cellular level. The focus of this study is on hemodynamic modifications induced in the aorta in the presence of a COA and a BAV. For this purpose, numerical investigations and magnetic resonance imaging measurements were conducted with different configurations: (1) normal: normal aorta and normal aortic valve; (2) isolated COA: aorta with COA (75% reduction by area) and normal aortic valve; (3) complex COA: aorta with the same severity of COA (75% reduction by area) and BAV. The results show that the coexistence of COA and BAV significantly alters blood flow in the aorta with a significant increase in the maximal velocity, secondary flow, pressure loss, time-averaged wall shear stress and oscillatory shear index downstream of the COA. These findings can contribute to a better understanding of why patients with complex COA have adverse outcome even following a successful surgery. PMID:24015239

Nanoparticles Effectively Target Rapamycin Delivery to Sites of Experimental Aortic Aneurysm in Rats.

PubMed

Shirasu, Takuro; Koyama, Hiroyuki; Miura, Yutaka; Hoshina, Katsuyuki; Kataoka, Kazunori; Watanabe, Toshiaki

2016-01-01

Several drugs targeting the pathogenesis of aortic aneurysm have shown efficacy in model systems but not in clinical trials, potentially owing to the lack of targeted drug delivery. Here, we designed a novel drug delivery system using nanoparticles to target the disrupted aortic aneurysm micro-structure. We generated poly(ethylene glycol)-shelled nanoparticles incorporating rapamycin that exhibited uniform diameter and long-term stability. When injected intravenously into a rat model in which abdominal aortic aneurysm (AAA) had been induced by infusing elastase, labeled rapamycin nanoparticles specifically accumulated in the AAA. Microscopic analysis revealed that rapamycin nanoparticles were mainly distributed in the media and adventitia where the wall structures were damaged. Co-localization of rapamycin nanoparticles with macrophages was also noted. Rapamycin nanoparticles injected during the process of AAA formation evinced significant suppression of AAA formation and mural inflammation at 7 days after elastase infusion, as compared with rapamycin treatment alone. Correspondingly, the activities of matrix metalloproteinases and the expression of inflammatory cytokines were significantly suppressed by rapamycin nanoparticle treatment. Our findings suggest that the nanoparticle-based delivery system achieves specific delivery of rapamycin to the rat AAA and might contribute to establishing a drug therapy approach targeting aortic aneurysm.

Nanoparticles Effectively Target Rapamycin Delivery to Sites of Experimental Aortic Aneurysm in Rats

PubMed Central

Shirasu, Takuro; Koyama, Hiroyuki; Miura, Yutaka; Hoshina, Katsuyuki; Kataoka, Kazunori; Watanabe, Toshiaki

2016-01-01

Several drugs targeting the pathogenesis of aortic aneurysm have shown efficacy in model systems but not in clinical trials, potentially owing to the lack of targeted drug delivery. Here, we designed a novel drug delivery system using nanoparticles to target the disrupted aortic aneurysm micro-structure. We generated poly(ethylene glycol)-shelled nanoparticles incorporating rapamycin that exhibited uniform diameter and long-term stability. When injected intravenously into a rat model in which abdominal aortic aneurysm (AAA) had been induced by infusing elastase, labeled rapamycin nanoparticles specifically accumulated in the AAA. Microscopic analysis revealed that rapamycin nanoparticles were mainly distributed in the media and adventitia where the wall structures were damaged. Co-localization of rapamycin nanoparticles with macrophages was also noted. Rapamycin nanoparticles injected during the process of AAA formation evinced significant suppression of AAA formation and mural inflammation at 7 days after elastase infusion, as compared with rapamycin treatment alone. Correspondingly, the activities of matrix metalloproteinases and the expression of inflammatory cytokines were significantly suppressed by rapamycin nanoparticle treatment. Our findings suggest that the nanoparticle-based delivery system achieves specific delivery of rapamycin to the rat AAA and might contribute to establishing a drug therapy approach targeting aortic aneurysm. PMID:27336852

Identification of vessel wall degradation in ascending thoracic aortic aneurysms with OCT

PubMed Central

Real, Eusebio; Val-Bernal, José Fernando; Revuelta, José M.; Pontón, Alejandro; Díez, Marta Calvo; Mayorga, Marta; López-Higuera, José M.; Conde, Olga M.

2014-01-01

Degradation of the wall of human ascending thoracic aorta has been assessed through Optical Coherence Tomography (OCT). OCT images of the media layer of the aortic wall exhibit micro-structure degradation in case of diseased aortas from aneurysmal vessels. The OCT indicator of degradation depends on the dimension of areas of the media layer where backscattered reflectivity becomes smaller due to a disorder on the morphology of elastin, collagen and smooth muscle cells (SMCs). Efficient pre-processing of the OCT images is required to accurately extract the dimension of degraded areas after an optimized thresholding procedure. OCT results have been validated against conventional histological analysis. The OCT qualitative assessment has achieved a pair sensitivity-specificity of 100%-91.6% in low-high degradation discrimination when a threshold of 4965.88µm2 is selected. This threshold suggests to have physiological meaning. The OCT quantitative evaluation of degradation achieves a correlation of 0.736 between the OCT indicator and the histological score. This in-vitro study can be transferred to the clinical scenario to provide an intraoperative assessment tool to guide cardiovascular surgeons in open repair interventions. PMID:25426332

Towards the evaluation of the pathological state of ascending thoracic aneurysms: integration of in-vivo measurements and hemodynamic simulations

NASA Astrophysics Data System (ADS)

Boccadifuoco, Alessandro; Mariotti, Alessandro; Celi, Simona; Martini, Nicola; Salvetti, Maria Vittoria

2016-11-01

Ascending thoracic aortic aneurysms are cardiovascular diseases consisting in a dilation of the ascending thoracic aorta. Since indicating a weakness of the arterial wall, they can lead to major complications with significant mortality rate. Clinical decisions about surgery are currently based on the maximum aortic diameter, but this single index does not seem a reliable indicator of the pathological state of the aorta. Numerical simulations of the blood flow inside the aneurysm may give supplementary information by quantifying important indices that are difficult to be measured, like the wall shear stress. Our aim is to develop an efficient platform in which in-vivo measurements are used to perform the hemodynamic simulations on a patient-specific basis. In particular, we used real geometries of thoracic aorta and focused on the use of clinical information to impose accurate boundary conditions at the inlet/outlets of the computational model. Stochastic analysis was also performed, to evaluate how uncertainties in the boundary parameters affect the main hemodynamic indicators, by considering both rigid and deformable walls. Stochastic calibration of numerical parameters against clinical data is in progress and results will be possibly shown.

Measurement of drug and macromolecule diffusion across atherosclerotic rabbit aorta ex vivo by attenuated total reflection-Fourier transform infrared imaging

NASA Astrophysics Data System (ADS)

Palombo, Francesca; Danoux, Charlène B.; Weinberg, Peter D.; Kazarian, Sergei G.

2009-07-01

Diffusion of two model drugs-benzyl nicotinate and ibuprofen-and the plasma macromolecule albumin across atherosclerotic rabbit aorta was studied ex vivo by attenuated total reflection-Fourier transform infrared (ATR-FTIR) imaging. Solutions of these molecules were applied to the endothelial surface of histological sections of the aortic wall that were sandwiched between two impermeable surfaces. An array of spectra, each corresponding to a specific location in the section, was obtained at various times during solute diffusion into the wall and revealed the distribution of the solutes within the tissue. Benzyl nicotinate in Ringer's solution showed higher affinity for atherosclerotic plaque than for apparently healthy tissue. Transmural concentration profiles for albumin demonstrated its permeation across the section and were consistent with a relatively low distribution volume for the macromolecule in the middle of the wall. The ability of albumin to act as a drug carrier for ibuprofen, otherwise undetected within the tissue, was demonstrated by multivariate subtraction image analysis. In conclusion, ATR-FTIR imaging can be used to study transport processes in tissue samples with high spatial and temporal resolution and without the need to label the solutes under study.

Respiratory Displacement of the Thoracic Aorta: Physiological Phenomenon With Potential Implications for Thoracic Endovascular Repair

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

Weber, Tim Frederik, E-mail: tim.weber@med.uni-heidelberg.d; Tetzlaff, Ralf; Rengier, Fabian

The purpose of this study was to assess the magnitude and direction of respiratory displacement of the ascending and descending thoracic aorta during breathing maneuvers. In 11 healthy nonsmokers, dynamic magnetic resonance imaging was performed in transverse orientation at the tracheal bifurcation during maximum expiration and inspiration as well as tidal breathing. The magnitude and direction of aortic displacement was determined relatively to resting respiratory position for the ascending (AA) and descending (DA) aorta. To estimate a respiratory threshold for occurrence of distinct respiratory aortic motion, the latter was related to the underlying change in anterior-posterior thorax diameter. Compound displacementmore » between maximum expiration and inspiration was 24.3 {+-} 6.0 mm for the AA in the left anterior direction and 18.2 {+-} 5.5 mm for the DA in the right anterior direction. The mean respiratory thorax excursion during tidal breathing was 8.9 {+-} 2.8 mm. The respiratory threshold, i.e., the increase in thorax diameter necessary to result in respiratory aortic displacement, was estimated to be 15.7 mm. The data suggest that after a threshold of respiratory thorax excursion is exceeded, respiration is accompanied by significant displacement of the thoracic aorta. Although this threshold may not be reached during tidal breathing in the majority of individuals, segmental differences during forced respiration impact on aortic geometry, may result in additional extrinsic forces on the aortic wall, and may be of significance for aortic prostheses designed for thoracic endovascular aortic repair.« less

Subclinical atherosclerosis and subsequent cognitive function.

PubMed

Rossetti, Heidi C; Weiner, Myron; Hynan, Linda S; Cullum, C Munro; Khera, Amit; Lacritz, Laura H

2015-07-01

To examine the relationship between measures of subclinical atherosclerosis and subsequent cognitive function. Participants from the Dallas Heart Study (DHS), a population-based multiethnic study of cardiovascular disease pathogenesis, were re-examined 8 years later (DHS-2) with the Montreal Cognitive Assessment (MoCA); N = 1904, mean age = 42.9, range 8-65. Associations of baseline measures of subclinical atherosclerosis (coronary artery calcium, abdominal aortic plaque, and abdominal aortic wall thickness) with MoCA scores measured at follow-up were examined in the group as a whole and in relation to age and ApoE4 status. A significant linear trend of successively lower MoCA scores with increasing numbers of atherosclerotic indicators was observed (F(3, 1150) = 5.918, p = .001). CAC was weakly correlated with MoCA scores (p = .047) and MoCA scores were significantly different between participants with and without CAC (M = 22.35 vs 23.69, p = 0.038). With the exception of a small association between abdominal AWT and MoCA in subjects over age 50, abdominal AWT and abdominal aortic plaque did not correlate with MoCA total score (p ≥ .052). Cognitive scores and atherosclerosis measures were not impacted by ApoE4 status (p ≥ .455). In this ethnically diverse population-based sample, subclinical atherosclerosis was minimally associated with later cognitive function in middle-aged adults. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Computational modelling of flow and tip variations of aortic cannulae in cardiopulmonary bypass procedure

NASA Astrophysics Data System (ADS)

Thomas, Siti A.; Empaling, Shirly; Darlis, Nofrizalidris; Osman, Kahar; Dillon, Jeswant; Taib, Ishkrizat; Khudzari, Ahmad Zahran Md

2017-09-01

Aortic cannulation has been the gold standard for maintaining cardiovascular function during open heart surgery while being connected onto the heart lung machine. These cannulation produces high velocity outflow which may lead to adverse effect on patient condition, especially sandblasting effect on aorta wall and blood cells damage. This paper reports a novel design that was able to decrease high velocity outflow. There were three design factors of that was investigated. The design factors consist of the cannula type, the flow rate, and the cannula tip design which result in 12 variations. The cannulae type used were the spiral flow inducing cannula and the standard cannula. The flow rates are varied from three to five litres per minute (lpm). Parameters for each cannula variation included maximum velocity within the aorta, pressure drop, wall shear stress (WSS) area exceeding 15 Pa, and impinging velocity on the aorta wall were evaluated. Based on the result, spiral flow inducing cannulae is proposed as a better alternatives due to its ability to reduce outflow velocity. Meanwhile, the pressure drop of all variations are less than the limit of 100 mmHg, although standard cannulae yielded better result. All cannulae show low reading of wall shear stress which decrease the possibilities for atherogenesis formation. In conclusion, as far as velocity is concerned, spiral flow is better compared to standard flow across all cannulae variations.

Inadvertent transarterial insertion of atrial and ventricular defibrillator leads.

PubMed

Issa, Ziad F; Rumman, Syeda S; Mullin, James C

2009-01-01

Inadvertent placement of pacemaker and implantable cardioverter-defibrillator (ICD) leads in the left ventricle (LV) is a rare but well-recognized complication of device implantation [1]. We report a case of inadvertent transarterial implantation of dual-chamber ICD leads; the ventricular lead positioned in the LV and the atrial lead positioned in the aortic root. The tip of the atrial lead migrated across the aortic wall and captured the epicardial surface of the left atrium. The diagnosis was made 5 years after the implantation procedure with no apparent adverse events directly related to left heart lead placement.

Infectious or Noninfectious? Ruptured, Thrombosed Inflammatory Aortic Aneurysm with Spondylolysis

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

Stefanczyk, Ludomir; Elgalal, Marcin, E-mail: telgalal@yahoo.co.uk; Papiewski, Andrzej

Osteolysis of vertebrae due to inflammatory aortic aneurysm is rarely observed. However, it is estimated that up to 10 % of infectious aneurysms coexist with bone tissue destruction, most commonly the vertebrae. Inflammatory aneurysms with no identified infection factor, along with infiltration of adjacent muscle and in particular extensive destruction of bone tissue have rarely been described in the literature. A case of inflammatory aneurysm with posterior wall rupture and inflammatory infiltration of the iliopsoas muscle and spine, together with extensive vertebral body destruction, is presented. The aneurysm was successfully treated with endovascular aneurysm repair EVAR.

Spontaneous aortic dissecting hematoma in two dogs.

PubMed

Boulineau, Theresa Marie; Andrews-Jones, Lydia; Van Alstine, William

2005-09-01

This report describes 2 cases of spontaneous aortic dissecting hematoma in young Border Collie and Border Collie crossbred dogs. Histology was performed in one of the cases involving an unusual splitting of the elastin present within the wall of the aorta, consistent with elastin dysplasia as described in Marfan syndrome in humans. The first case involved a young purebred Border Collie that died suddenly and the second case involved a Border Collie crossbred dog that died after a 1-month history of seizures. Gross lesions included pericardial tamponade with dissection of the ascending aorta in the former case and thoracic cavity hemorrhage, mediastinal hematoma, and aortic dissection in the latter. Histologic lesions in the case of the Border Collie crossbred dog included a dissecting hematoma of the ascending aorta with elastin dysplasia and right axillary arterial intimal proliferation.

Endothelium as a Potential Target for Treatment of Abdominal Aortic Aneurysm

PubMed Central

Sun, Jingyuan; Deng, Hongping; Zhou, Zhen

2018-01-01

Abdominal aortic aneurysm (AAA) was previously ascribed to weaken defective medial arterial/adventitial layers, for example, smooth muscle/fibroblast cells. Therefore, besides surgical repair, medications targeting the medial layer to strengthen the aortic wall are the most feasible treatment strategy for AAA. However, so far, it is unclear whether such drugs have any beneficial effect on AAA prognosis, rate of aneurysm growth, rupture, or survival. Notably, clinical studies have shown that AAA is highly associated with endothelial dysfunction in the aged population. Additionally, animal models of endothelial dysfunction and endothelial nitric oxide synthase (eNOS) uncoupling had a very high rate of AAA formation, indicating there is crucial involvement of the endothelium and a possible pharmacological solution targeting the endothelium in AAA treatment. Endothelial cells have been found to trigger vascular wall remodeling by releasing proteases, or recruiting macrophages along with other neutrophils, into the medial layer. Moreover, inflammation and oxidative stress of the arterial wall were induced by endothelial dysfunction. Interestingly, there is a paradoxical differential correlation between diabetes and aneurysm formation in retinal capillaries and the aorta. Deciphering the significance of such a difference may explain current unsuccessful AAA medications and offer a solution to this treatment challenge. It is now believed that AAA and atherosclerosis are two separate but related diseases, based on their different clinical patterns which have further complicated the puzzle. Therefore, a thorough investigation of the interaction between endothelium and medial/adventitial layer may provide us a better understanding and new perspective on AAA formation, especially after taking into account the importance of endothelium in the development of AAA. Moreover, a novel medication strategy replacing the currently used, but suboptimal treatments for AAA, could be informed with this analysis. PMID:29849906

Tissue factor levels and the fibrinolytic system in thin and thick intraluminal thrombus and underlying walls of abdominal aortic aneurysms.

PubMed

Siennicka, Aldona; Zuchowski, Marta; Kaczmarczyk, Mariusz; Cnotliwy, Miłosław; Clark, Jeremy Simon; Jastrzębska, Maria

2018-03-20

The hemostatic system cooperates with proteolytic degradation in processes allowing abdominal aortic aneurysm (AAA) formation. In previous studies, it has been suggested that aneurysm rupture depends on intraluminal thrombus (ILT) thickness, which varies across each individual aneurysm. We hypothesized that hemostatic components differentially accumulate in AAA tissue in relation to ILT thickness. Thick (A1) and thin (B1) segments of ILTs and aneurysm wall sections A (adjacent to A1) and B (adjacent to B1) from one aneurysm sac were taken from 35 patients undergoing elective repair. Factor levels were measured using enzyme-linked immunosorbent assay of protein extract. Tissue factor (TF) activities were significantly higher in thinner segments of AAA (B1 vs A1, P = .003; B vs A, P < .001; B vs A1, P < .001; B vs B1, P = .001). Significantly higher tissue plasminogen activator was found in thick thrombus-covered wall segments (A) than in B, A1, and B1 (P = .015, P < .001, and P < .001, respectively). Plasminogen concentrations were highest in ILT. Concentrations of α 2 -antiplasmin in thin ILT adjacent walls (B) were higher compared with wall (A) adjacent to thick ILT (P = .021) and thick ILT (A1; P < .001). Significant correlations between levels of different factors were mostly found in thick ILT (A1). However, no correlations were found at B sites, except for a correlation between plasmin and TF activities (r = 0.55; P = .004). These results suggest that higher TF activities are present in thinner AAA regions. These parameters and local fibrinolysis may be part of the processes leading to destruction of the aneurysm wall. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Predictive factor of secondary tricuspid regurgitation after aortic valve replacement for aortic stenosis: the importance of myocardial hypertrophy and diastolic dysfunction.

PubMed

Igarashi, Takashi; Tanji, Masahiro; Takahashi, Koki; Ishida, Keiichi; Sasaki, Satomi; Yokoyama, Hitoshi

2017-05-01

The aim of this study is to determine the predictors of secondary tricuspid regurgitation after aortic valve replacement for aortic stenosis. Seventy-one patients, who underwent aortic valve replacement for aortic stenosis at our institute from January 2006 to July 2011, were divided into two groups: an STR group, which included 15 patients with moderate or greater than moderate secondary tricuspid regurgitation at a follow-up visit and a control group. Echocardiography was performed before surgery, at discharge, and at a late follow-up visit (mean follow-up 36 ± 19 months, range 0-77). Preoperatively, the number of women (p < .01), body surface area (p < .001), and relative wall thickness (0.60 ± 0.15 vs 0.71 ± 0.13, p = .022) showed significant differences between the two groups. At a follow-up visit, moderate or severe mitral regurgitation (p = .0001) and severe diastolic dysfunction (p = .003) showed significant differences between the two groups. In the Cox regression analysis, moderate or severe mitral regurgitation at follow-up (p = .038, hazard ratio 4.394, 95% CI 1.085-17.791) was the only independent predictor of secondary tricuspid regurgitation. This study suggested that preoperative concentric myocardial hypertrophy and diastolic dysfunction were associated with development of the secondary tricuspid regurgitation at late follow-up.

Tribbles 3: A potential player in diabetic aortic remodelling.

PubMed

Ti, Yun; Xie, Guo-lu; Wang, Zhi-hao; Ding, Wen-yuan; Zhang, Yun; Zhong, Ming; Zhang, Wei

2016-01-01

Tribbles 3, whose expression is up-regulated by insulin resistance, was confirmed to be involved in diabetic cardiomyopathy in our previous study. However, it is not known whether Tribbles 3 has a role on conduit arteries such as the aorta in diabetes. Type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin. We evaluated the characteristics of diabetic rats by serial ultrasonography and histopathologic analyses of aortic wall architecture. Diabetic rats displayed increased aortic medial thickness, excessive collagen deposition, diminished elastic fibres and reduced vascular compliance together with Tribbles 3 overexpression. To further investigate the role of Tribbles 3 in aortic remodelling, we used Tribbles 3 gene silencing in vivo 12 weeks after onset of diabetes. Silence of Tribbles 3 significantly reversed pathological aortic remodelling without blood pressure modification. In Tribbles 3-small interfering RNA group, medial thickness and perivascular fibrosis were markedly decreased; moreover, there were prominent reductions in collagen content and collagen/elastin ratio, resulting in an improved arterial compliance. Additionally, with Tribbles 3 silencing, the diminished phosphorylation of PI3K/Akt was restored, and increased activation of MKK4/JNK was decreased. Silence of Tribbles 3 is potent in mediating reversal of aortic remodelling, implicating that Tribbles 3 is proposed to be a potential therapeutic target for vascular complication in diabetes. © The Author(s) 2015.

Optimizing 18F-FDG PET/CT Imaging of Vessel Wall Inflammation –The Impact of 18F-FDG Circulation Time, Injected Dose, Uptake Parameters, and Fasting Blood Glucose Levels

PubMed Central

Bucerius, Jan; Mani, Venkatesh; Moncrieff, Colin; Machac, Josef; Fuster, Valentin; Farkouh, Michael E.; Tawakol, Ahmed; Rudd, James H. F.; Fayad, Zahi A.

2014-01-01

Purpose 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is increasingly used for imaging of vessel wall inflammation. However, limited data is available regarding the impact of methodological variables, i. e. patient’s pre-scan fasting glucose, the FDG circulation time, the injected FDG dose, and of different FDG uptake parameters, in vascular FDG-PET imaging. Methods 195 patients underwent vascular FDG-PET/CT of the aorta and the carotids. Arterial standard uptake values (meanSUVmax) as well as target-to-background-ratios (meanTBRmax) and the FDG blood pool activity in the superior vein cava (SVC) and the jugular veins (JV) were quantified. Vascular FDG uptake classified according to tertiles of patient’s pre-scan fasting glucose levels, the FDG circulation time, and the injected FDG dose was compared using ANOVA. Multivariate regression analyses were performed to identify the potential impact of all variables described on the arterial and blood pool FDG uptake. Results Tertile analyses revealed FDG circulation times of about 2.5 h and prescan glucose levels of less than 7.0 mmol/l showing favorable relations between the arterial and blood pool FDG uptake. FDG circulation times showed negative associations with the aortic meanSUVmax values as well as SVC- and JV FDG blood pool activity but a positive correlation with the aortic- and carotid meanTBRmax values. Pre-scan glucose was negatively associated with aortic- and carotid meanTBRmax and carotid meanSUVmax values, but correlated positively with the SVC blood pool uptake. Injected FDG dose failed to show any significant association with the vascular FDG uptake. Conclusion FDG circulation times and pre-scan blood glucose levels significantly impact FDG uptake within the aortic and carotid wall and may bias the results of image interpretation in patients undergoing vascular FDG-PET/CT. FDG dose injected was less critical. Therefore, circulation times of about 2.5 h and pre-scan glucose levels less than 7.0 mmol/l should be preferred in this setting. PMID:24271038

Structural modifications in the arterial wall during physiological aging and as a result of diabetes mellitus in a mouse model: are the changes comparable?

PubMed

Prévost, G; Bulckaen, H; Gaxatte, C; Boulanger, E; Béraud, G; Creusy, C; Puisieux, F; Fontaine, P

2011-04-01

Vascular accelerated aging represents the major cause of morbidity and mortality in subjects with diabetes mellitus. In the present study, our aim was to compare premature functional and morphological changes in the arterial wall resulting from streptozotocin (STZ)-induced diabetes mellitus in mice over a short-term period with those that develop during physiological aging. The effect of aminoguanidine (AG) on the prevention of these alterations in the diabetic group was also analyzed. The vascular relaxation response to acetylcholine (ACh) in the mouse was tested in isolated segments of phenylephrine (Phe)-precontracted aorta at 2, 4 and 8 weeks (wk) of STZ-induced diabetes and compare to 12- and 84-wk-old mice. Aortic structural changes were investigated, and receptor for AGE (RAGE) aortic expression was quantified by western blot. Compared to the 12-wk control group (76 ± 5%), significant endothelium-dependant relaxation (EDR) impairment was found in the group of 12-wk-old mice, which underwent a 4-wk diabetes-inducing STZ treatment (12wk-4WD) (52 ± 4%; P < 0.01) and was yet more apparent in the group of 16-wk-old mice, which underwent an 8-wk diabetes-inducing STZ treatment (16wk-8WD) (34 ± 4%; P < 0.001). The alteration in EDR was relatively comparable between the diabetic 12wk-4WD group and the 84-wk-old group (52.7 ± 4 vs. 48 ± 4%). Intima/media aortic thickening and aortic structural changes were significantly increased in the diabetic 12wk-4WD group and were even more apparent in the 84-wk group compared to the 12-wk controls. AG treatment in the 12wk-4WD+AG diabetic group significantly improved EDR, decreased RAGE expression and showed an aging preventive effect on the structural changes of the arterial wall. Our study compared EDR linked to physiological aging with that observed in the case of STZ-induced diabetes over a short-term period, and demonstrated the beneficial effect of AG. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Nicotinamide Phosphoribosyltransferase in Smooth Muscle Cells Maintains Genome Integrity, Resists Aortic Medial Degeneration, and Is Suppressed in Human Thoracic Aortic Aneurysm Disease.

PubMed

Watson, Alanna; Nong, Zengxuan; Yin, Hao; O'Neil, Caroline; Fox, Stephanie; Balint, Brittany; Guo, Linrui; Leo, Oberdan; Chu, Michael W A; Gros, Robert; Pickering, J Geoffrey

2017-06-09

The thoracic aortic wall can degenerate over time with catastrophic consequences. Vascular smooth muscle cells (SMCs) can resist and repair artery damage, but their capacities decline with age and stress. Recently, cellular production of nicotinamide adenine dinucleotide (NAD + ) via nicotinamide phosphoribosyltransferase (Nampt) has emerged as a mediator of cell vitality. However, a role for Nampt in aortic SMCs in vivo is unknown. To determine whether a Nampt-NAD + control system exists within the aortic media and is required for aortic health. Ascending aortas from patients with dilated aortopathy were immunostained for NAMPT, revealing an inverse relationship between SMC NAMPT content and aortic diameter. To determine whether a Nampt-NAD + control system in SMCs impacts aortic integrity, mice with Nampt -deficient SMCs were generated. SMC- Nampt knockout mice were viable but with mildly dilated aortas that had a 43% reduction in NAD + in the media. Infusion of angiotensin II led to aortic medial hemorrhage and dissection. SMCs were not apoptotic but displayed senescence associated-ß-galactosidase activity and upregulated p16, indicating premature senescence. Furthermore, there was evidence for oxidized DNA lesions, double-strand DNA strand breaks, and pronounced susceptibility to single-strand breakage. This was linked to suppressed poly(ADP-ribose) polymerase-1 activity and was reversible on resupplying NAD + with nicotinamide riboside. Remarkably, we discovered unrepaired DNA strand breaks in SMCs within the human ascending aorta, which were specifically enriched in SMCs with low NAMPT. NAMPT promoter analysis revealed CpG hypermethylation within the dilated human thoracic aorta and in SMCs cultured from these tissues, which inversely correlated with NAMPT expression. The aortic media depends on an intrinsic NAD + fueling system to protect against DNA damage and premature SMC senescence, with relevance to human thoracic aortopathy. © 2017 American Heart Association, Inc.

Low-density lipoprotein transport in blood vessel walls of squirrel monkeys

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

Tompkins, R.G.; Yarmush, M.L.; Schnitzer, J.J.

1989-08-01

Transmural accumulations of low-density lipoprotein (LDL) were examined in the blood vessel walls of four squirrel monkeys. Vascular wall concentrations of LDL were measured using quantitative autoradiography after {sup 125}I-labeled LDL circulation for 30 min. Profiles of relative tissue concentration from different sections in the same region were similar to each other, and there was little animal-to-animal variation. Concentrations were highest near the luminal endothelium, lower near the medial-adventitial border, and lowest within the media. Profiles from different regions fell into three groups: (1) aortic samples had steep intimal concentration gradients and near-zero media concentrations; (2) the iliac, femoral, popliteal,more » and common carotid arteries had higher intimal concentrations than group 1 but had similar concentrations deep within the media; and (3) the cerebral and coronary arteries, inferior vena cava, and pulmonary artery had intimal concentrations that were similar to group 2, but the concentrations deep within the media were greater than either groups 1 or 2. Arterial bifurcation profiles from the inner wall and the outer walls were similar to each other and to profiles from the upstream and downstream areas. Out of 280 total sites examined, 15 examples of profiles with substantially increased concentrations near the luminal endothelium were found scattered throughout the cardiovascular system, demonstrating that there are focal regions throughout the cardiovascular system which have greatly increased {sup 125}I-LDL transendothelial permeability.« less

Effects of Aortic Irregularities on the Blood Flow

NASA Astrophysics Data System (ADS)

Gutmark-Little, Iris; Prahl-Wittberg, Lisa; van Wyk, Stevin; Mihaescu, Mihai; Fuchs, Laszlo; Backeljauw, Philippe; Gutmark, Ephraim

2013-11-01

Cardiovascular defects characterized by geometrical anomalies of the aorta and its effect on the blood flow are investigated. The flow characteristics change with the aorta geometry and the rheological properties of the blood. Flow characteristics such as wall shear stress often play an important role in the development of vascular disease. In the present study, blood is considered to be non-Newtonian and is modeled using the Quemada model, an empirical model that is valid for different red blood cell loading. Three patient-specific aortic geometries are studied using Large Eddy Simulations (LES). The three geometries represent malformations that are typical in patients populations having a genetic disorder called Turner syndrome. The results show a highly complex flow with regions of recirculation that are enhanced in two of the three aortas. Moreover, blood flow is diverted, due to the malformations, from the descending aorta to the three side branches of the arch. The geometry having an elongated transverse aorta has larger areas of strong oscillatory wall shear stress.

Effect of acute high-intensity resistance exercise on optic nerve sheath diameter and ophthalmic artery blood flow pulsatility.

PubMed

Lefferts, W K; Hughes, W E; Heffernan, K S

2015-12-01

Exertional hypertension associated with acute high-intensity resistance exercise (RE) increases both intravascular and intracranial pressure (ICP), maintaining cerebrovascular transmural pressure. Carotid intravascular pressure pulsatility remains elevated after RE. Whether ICP also remains elevated after acute RE in an attempt to maintain the vessel wall transmural pressure is unknown. Optic nerve sheath diameter (ONSD), a valid proxy of ICP, was measured in 20 participants (6 female; 24 ± 4 yr, 24.2 ± 3.9 kg m(-)(2)) at rest (baseline), following a time-control condition, and following RE (5 sets, 5 repetition maximum bench press, 5 sets 10 repetition maximum biceps curls) using ultrasound. Additionally, intracranial hemodynamic pulsatility index (PI) was assessed in the ophthalmic artery (OA) by using Doppler. Aortic pulse wave velocity (PWV) was obtained from synthesized aortic pressure waveforms obtained via a brachial oscillometric cuff and carotid pulse pressure was measured by using applanation tonometry. Aortic PWV (5.2 ± 0.5-6.0 ± 0.7 m s(-1), P < 0.05) and carotid pulse pressure (45 ± 17-59 ± 19 mm Hg, P < 0.05) were significantly elevated post RE compared with baseline. There were no significant changes in ONSD (5.09 ± 0.7-5.09 ± 0.7 mm, P > 0.05) or OA flow PI (1.35 ± 0.2-1.38 ± 0.3, P > 0.05) following acute RE. In conclusion, during recovery from acute high-intensity RE, there are increases in aortic stiffness and extracranial pressure pulsatility in the absence of changes in ICP and flow pulsatility. These findings may have implications for alterations in cerebral transmural pressure and cerebral aneurysmal wall stress following RE.

Personalized design and virtual evaluation of physician-modified stent grafts for juxta-renal abdominal aortic aneurysms

NASA Astrophysics Data System (ADS)

Sanathkhani, Soroosh; Shroff, Sanjeev G.; Menon, Prahlad G.

2017-02-01

Endovascular aneurysm repair (EVAR) of juxtarenal aortic aneurysms (JAA) is particularly challenging owing to the requirement of suprarenal EVAR graft fixation, which has been associated with significant declines in long term renal function. Therefore, the ability to design fenestrated EVAR grafts on a personalized basis in order to ensure visceral and renal perfusion, is highly desirable. The objectives of this study are: a) To demonstrate novel 3D geometric methods to virtually design and deploy EVAR grafts into a virtually designed JAA, by applying a custom surface mesh deformation tool to a patient-specific descending aortic model reconstructed from computed tomographic (CT) images; and b) To virtually evaluate patient-specific renal flow and wall stresses in these patient-specific virtually EVAR geometries, using computational fluid dynamics (CFD). The presented framework may provide the modern cardiovascular surgeon the ability to leverage non-invasive, pre-operative imaging equipment to personalize and guide EVAR therapeutic strategy. Our CFD studies revealed that virtual EVAR grafting of a patient-specific JAA, with optimal fenestration sites and renal stenting, led to a 179.67±15.95% and 1051.43±18.34% improvement in right and left renal flow rates, respectively, when compared with the baseline patient-specific aortic geometry with renal stenoses, whereas a right and left renal flow improved by 36.44±2.24% and 885.93±12.41%, respectively, relative to the equivalently modeled JAA with renal stenoses, considering averages across the three simulated inflow rate cases. The proposed framework have utility to iteratively optimize suprarenal EVAR fixation length and achieve normal renal wall shear stresses and streamlined juxtarenal hemodynamics.

Dacron graft as replacement to dissected aorta: A three-dimensional fluid-structure-interaction analysis.

PubMed

Jayendiran, R; Nour, B M; Ruimi, A

2018-02-01

Aortic dissection (AD) is a serious medical condition characterized by a tear in the intima, the inner layer of the aortic walls. In such occurrence, blood is being diverted to the media (middle) layer and may result in patient death if not quickly attended. In the case where the diseased portion of the aorta needs to be replaced, one common surgical technique is to use a graft made of Dacron, a synthetic fabric. We investigate the response of a composite human aortic segment-Dacron graft structure subjected to blood flow using the three-dimensional fluid-structure-interaction (FSI) capability in Abaqus. We obtain stress and strain profiles in each of the three layers of the aortic walls as well as in the Dacron graft. Results are compared when elastic and hyperelastic models are used and when isotropy vs. anisotropy is assumed. The more complex case (hyperelastic-anisotropy) is represented by the Holzapfel-Gasser-Ogden (HGO) model which also accounts for the orientation of the fibers present in the tissues. The fluid flow is taken as Newtonian, incompressible, pulsatile and turbulent. The simulation show that for all the cases, the von Mises stress distribution at aorta-Dacron interface is well below the ultimate strength of the aorta. No significant change in radial displacement at the interface of the two materials due to blood flow is observed. Computation cost is also addressed and results show that the hyperelastic-anisotropic model takes about three times longer to run than the elastic isotropic case. Trade-off between accuracy and computational cost has to be weighted. Copyright © 2017 Elsevier Ltd. All rights reserved.

Classification of gutter type in parallel stenting during endovascular aortic aneurysm repair.

PubMed

Overeem, Simon P; Boersen, Johannes T; Schuurmann, Richte C L; Groot Jebbink, Erik; Slump, Cornelis H; Reijnen, Michel M P J; de Vries, Jean-Paul P M

2017-08-01

Gutters can be described as the loss of continuous apposition between the main body of the endograft, the chimney stent graft, and the aortic wall. Gutters have been associated with increased risk of type IA endoleaks and are considered to be the Achilles' heel of chimney endovascular aneurysm repair (ch-EVAR). However, there is no classification yet to classify and quantify gutter types after ch-EVAR. Different gutter types can be distinguished by their morphologic appearance in two- and three-dimensional views and reconstructed slices perpendicular to the center lumen line. Three main categories are defined by (1) the most proximal beginning of the gutter, (2) the length of gutter alongside the endograft, and (3) its distal end. Type A gutters originate at the proximal fabric of an endograft, type B gutters originate as loss of apposition of the chimney stent graft in the branch vessel, and type C gutters start below the fabric of the endograft. To determine eventual changes of gutter size during follow-up computed tomography angiograms (CTAs), measurements may be performed with dedicated software on the follow-up CTA scan to assess the extent of gutters over the aortic circumference, ranging from 0° to 360° of freedom, together with the maximum gap between the endograft material and the aortic wall as it appears on reconstructed axial CTA scan slices. The proposed gutter classification enables a uniform nomenclature in the current ch-EVAR literature and a more accurate risk assessment of gutter-associated endoleaks. Moreover, it allows monitoring of eventual progression of gutter size during follow-up. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Evaluation of the levels of metalloproteinsase-2 in patients with abdominal aneurysm and abdominal hernias.

PubMed

Antoszewska, Magdalena

2013-05-01

Abdominal aortic aneurysms and abdominal hernias become an important health problems of our times. Abdominal aortic aneurysm and its rupture is one of the most dangerous fact in vascular surgery. There are some theories pointing to a multifactoral genesis of these kinds of diseases, all of them assume the attenuation of abdominal fascia and abdominal aortic wall. The density and continuity of these structures depend on collagen and elastic fibers structure. Reducing the strength of the fibers may be due to changes in the extracellular matrix (ECM) by the proteolytic enzymes-matrix metalloproteinases (MMPs) that degrade extracellular matrix proteins. These enzymes play an important role in the development of many disease: malignant tumors (colon, breast, lung, pancreas), cardiovascular disease (myocardial infarction, ischemia-reperfusion injury), connective tissue diseases (Ehler-Danlos Syndrome, Marfan's Syndrome), complications of diabetes (retinopathy, nephropathy). One of the most important is matrix metalloproteinase-2 (MMP-2). The aim of the study was an estimation of the MMP-2 blood levels in patients with abdominal aortic aneurysm and primary abdominal hernia, and in patients with only abdominal aortic aneurysm. The study involved 88 patients aged 42 to 89 years, including 75 men and 13 women. Patients were divided into two groups: patients with abdominal aortic aneurysm and primary abdominal hernia (45 persons, representing 51.1% of all group) and patients with only abdominal aortic aneurysm (43 persons, representing 48,9% of all group). It was a statistically significant increase in MMP-2 blood levels in patients with abdominal aortic aneurysm and primary abdominal hernia compared to patients with only abdominal aortic aneurysm. It was a statistically significant increase in the prevalence of POCHP in patients with only abdominal aortic aneurysm compared to patients with abdominal aortic aneurysm and primary abdominal hernia. Statistically significant higher MMP-2 blood levels in patients with abdominal aortic aneurysm and primary abdominal hernia seems shows that this enzyme plays a role in the pathogenesis of primary abdominal hernias. The observed distribution of MMP-2 blood levels in patients with abdominal aortic aneurysm and primary abdominal hernia may raise the conclusion that this enzyme determines the presence of multi-organ failure of the connective tissue--the patients with only abdominal aortic aneurysm had significantly lower MMP-2 blood levels.

Fluid dynamics of aortic valve stenosis

NASA Astrophysics Data System (ADS)

Keshavarz-Motamed, Zahra; Maftoon, Nima

2009-11-01

Aortic valve stenosis, which causes considerable constriction of the flow passage, is one of the most frequent cardiovascular diseases and is the most common cause of the valvular replacements which take place for around 100,000 per year in North America. Furthermore, it is considered as the most frequent cardiac disease after arterial hypertension and coronary artery disease. The objective of this study is to develop an analytical model considering the coupling effect between fluid flow and elastic deformation with reasonable boundary conditions to describe the effect of AS on the left ventricle and the aorta. The pulsatile and Newtonian blood flow through aortic stenosis with vascular wall deformability is analyzed and its effects are discussed in terms of flow parameters such as velocity, resistance to flow, shear stress distribution and pressure loss. Meanwhile we developed analytical expressions to improve the comprehension of the transvalvular hemodynamics and the aortic stenosis hemodynamics which is of great interest because of one main reason. To medical scientists, an accurate knowledge of the mechanical properties of whole blood flow in the aorta can suggest a new diagnostic tool.

Hemodynamics of the Aortic Jet and Implications for Detection of Aortic Stenosis Murmurs

NASA Astrophysics Data System (ADS)

Zhu, Chi; Seo, Junghee; Bakhshaee, Hani; Mittal, Rajat

2016-11-01

Cardiac auscultation with a stethoscope has served as the primary method for qualitative screening of cardiovascular conditions for over a hundred years. However, a lack of quantitative understanding of the flow mechanism(s) responsible for the generation of the murmurs, as well as the effect of intervening tissue on the propagation of these murmurs has been a significant limiting factor in the advancement of automated cardiac auscultation. In this study, a multiphysics computational modeling approach is used to investigate these issues. Direct numerical simulation (DNS) is used to explore the fluid dynamics of the jets formed at the aortic valve and the pressure fluctuations generated by the interaction of this jet with the aortic wall. Subsequently, structural wave propagation in the tissue is resolved by a high-order, linear viscoelastic wave solver in order to explore the propagation of the murmurs through a tissue-like material. The implications of these results for cardiac auscultation are discussed. The authors would like to acknowledge the financial support from NSF Grants IIS-1344772, CBET-1511200, and computational resource by XSEDE NSF Grant TG-CTS100002.

Inflammatory cell phenotypes in AAAs: their role and potential as targets for therapy.

PubMed

Dale, Matthew A; Ruhlman, Melissa K; Baxter, B Timothy

2015-08-01

Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused ≈15 000 deaths annually in the United States. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4(+) T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Proinflammatory CD4(+) T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to proinflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the proinflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. © 2015 American Heart Association, Inc.

Inflammatory cell phenotypes in AAAs; their role and potential as targets for therapy

PubMed Central

Dale, Matthew A; Ruhlman, Melissa K.; Baxter, B. Timothy

2015-01-01

Abdominal aortic aneurysms are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused approximately 15,000 deaths annually in the U.S. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4+ T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Pro-inflammatory CD4+ T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to pro-inflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the pro-inflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. PMID:26044582

Effect of selenium and omega-3 fatty acids on selected risk factors for heart disease

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

Mathews, A.H.; Hancock, R.C.; Christensen, M.J.

1986-03-01

Male weanling Sprague-Dawley rats were fed for 6 months a Torula yeast basal diet supplemented with one of three levels of Selenium (Se) (0, 0.1, or 1.0 ppm as Na/sub 2/-SeO/sub 3/), with or without a marine oil supplement (MaxEPA, Seven Seas, Hull, Eng.) added at 5% in a 3 x 2 factorial design. Dependent variables measured included: liver and platelet Se-glutathione peroxidase, (Se-GSH-Px); weight gain; relative weights (percent of body weight) of heart and a standardized section of aorta; and ADP-induced platelet aggregation. Dietary Se supplementation increased weight gain, liver and platelet Se-GSH-Px, and decreased relative heart and aortamore » weight (p < .001). MaxEPA significantly decreased platelet Se-GSH-Px (p < .05). Histological examination showed focal disruption of elastic fibers in aortic segments from rats fed the following diets: 0 Se without MaxEPA, 0 Se with MaxEPA, and 0.1 Se with MaxEPA. There were no significant differences in platelet aggregation among dietary groups. These findings suggest the following: (1) Se may be required for maintenance of normal integrity of the elastic tissue of the aortic wall; (2) high levels of polyunsaturates in the diet may compromise the protective effect of Se on elastic fibers in the aortic wall.« less

Decreased expression of γ-carboxylase in diabetes-associated arterial stiffness: impact on matrix Gla protein.

PubMed

Doyon, Marielle; Mathieu, Patrick; Moreau, Pierre

2013-02-01

Arterial stiffness is accelerated in type 1 diabetic patients. Medial artery calcification (MAC) contributes to the development of arterial stiffness. Vitamin K oxidoreductase (VKOR) reduces the vitamin K required by γ-carboxylase to activate matrix γ-carboxyglutamic acid (Gla) protein (MGP), an inhibitor of vascular calcification. This study aimed to evaluate the hypothesis that diabetes reduces the γ-carboxylation of MGP in the aortic wall, leading to increased vascular calcification, and the role of γ-carboxylase and VKOR in this γ-carboxylation deficit. Type 1 diabetes was induced in male Wistar rats with a single ip injection of streptozotocin. Augmentation of arterial stiffness in diabetic rats was shown by a 44% increase in aortic pulse wave velocity. Aortic and femoral calcification were increased by 26 and 56%, respectively. γ-Carboxylated MGP (cMGP, active) was reduced by 36% and the aortic expression of γ-carboxylase was reduced by 58%. Expression of γ-carboxylase correlated with cMGP (r= 0.59) and aortic calcification (r = -0.57). VKOR aortic expression and activity were not modified by diabetes. Vitamin K plasma concentrations were increased by 191% in diabetic rats. In ex vivo experiments with aortic rings, vitamin K supplementation prevented the glucose-induced decrease in γ-carboxylase expression. Our results suggest that reduced cMGP, through an impaired expression of γ-carboxylase, is involved in the early development of MAC in diabetes, and therefore, in the acceleration of arterial stiffness. A defect in vitamin K uptake by target cells could also be involved.

Influence of the tilt angle of Percutaneous Aortic Prosthesis on Velocity and Shear Stress Fields

PubMed Central

Gomes, Bruno Alvares de Azevedo; Camargo, Gabriel Cordeiro; dos Santos, Jorge Roberto Lopes; Azevedo, Luis Fernando Alzuguir; Nieckele, Ângela Ourivio; Siqueira-Filho, Aristarco Gonçalves; de Oliveira, Glaucia Maria Moraes

2017-01-01

Background Due to the nature of the percutaneous prosthesis deployment process, a variation in its final position is expected. Prosthetic valve placement will define the spatial location of its effective orifice in relation to the aortic annulus. The blood flow pattern in the ascending aorta is related to the aortic remodeling process, and depends on the spatial location of the effective orifice. The hemodynamic effect of small variations in the angle of inclination of the effective orifice has not been studied in detail. Objective To implement an in vitro simulation to characterize the hydrodynamic blood flow pattern associated with small variations in the effective orifice inclination. Methods A three-dimensional aortic phantom was constructed, reproducing the anatomy of one patient submitted to percutaneous aortic valve implantation. Flow analysis was performed by use of the Particle Image Velocimetry technique. The flow pattern in the ascending aorta was characterized for six flow rate levels. In addition, six angles of inclination of the effective orifice were assessed. Results The effective orifice at the -4º and -2º angles directed the main flow towards the anterior wall of the aortic model, inducing asymmetric and high shear stress in that region. However, the effective orifice at the +3º and +5º angles mimics the physiological pattern, centralizing the main flow and promoting a symmetric distribution of shear stress. Conclusion The measurements performed suggest that small changes in the angle of inclination of the percutaneous prosthesis aid in the generation of a physiological hemodynamic pattern, and can contribute to reduce aortic remodeling. PMID:28793046

Hypoperfusion of the Adventitial Vasa Vasorum Develops an Abdominal Aortic Aneurysm

PubMed Central

Sasaki, Takeshi; Sano, Masaki; Yamamoto, Naoto; Saito, Takaaki; Inuzuka, Kazunori; Hayasaka, Takahiro; Goto-Inoue, Naoko; Sugiura, Yuki; Sato, Kohji; Kugo, Hirona; Moriyama, Tatsuya; Konno, Hiroyuki; Setou, Mitsutoshi; Unno, Naoki

2015-01-01

The aortic wall is perfused by the adventitial vasa vasorum (VV). Tissue hypoxia has previously been observed as a manifestation of enlarged abdominal aortic aneurysms (AAAs). We sought to determine whether hypoperfusion of the adventitial VV could develop AAAs. We created a novel animal model of adventitial VV hypoperfusion with a combination of a polyurethane catheter insertion and a suture ligation of the infrarenal abdominal aorta in rats. VV hypoperfusion caused tissue hypoxia and developed infrarenal AAA, which had similar morphological and pathological characteristics to human AAA. In human AAA tissue, the adventitial VV were stenotic in both small AAAs (30–49 mm in diameter) and in large AAAs (> 50 mm in diameter), with the sac tissue in these AAAs being ischemic and hypoxic. These results indicate that hypoperfusion of adventitial VV has critical effects on the development of infrarenal AAA. PMID:26308526

Deadly case of Pasteurella multocida aortitis and mycotic aneurysm following a cat bite.

PubMed

Cho, Dennis Dane; Berliner, Yaniv; Carr, David

2016-06-16

Animal bites are frequently encountered in the emergency department (ED). Aortitis leading to mycotic abdominal aortic aneurysm is a rare and potentially deadly complication of Pasteurella multocida (P. multocida) following an animal bite. We present the case of a 68-year-old male who presented to the ED after falling at home. He complained of weakness and abdominal pain. He was in septic shock and was treated empirically with broad-spectrum antibiotics and intravenous fluids. He reported previous antibiotic treatment of a cellulitis secondary to a cat bite injury to his right thumb four weeks prior. Abdominal ultrasound and subsequent computed tomography scan revealed a leaking mycotic abdominal aneurysm that was surgically repaired. Blood cultures and aortic wall tissue cultures grew P. multocida. Given how common animal bite presentations are in the ED, this case highlights the need to consider aortitis and mycotic abdominal aortic aneurysm in an unwell patient with an animal bite.

Evaluation of the effects of glimepiride (Amaryl) and repaglinide (novoNorm) on atherosclerosis progression in high cholesterol-fed male rabbits.

PubMed

Hadi, Najah R; Al-Amran, Fadhil; Hussein, Mohammad A A; Rezeg, Fadhil A

2012-01-01

Atherosclerosis is an inflammatory disease of the blood vessel wall, characterized in early stages by endothelial dysfunction, recruitment and activation of monocyte/macrophages. Glimepiride is one of the third generation sulphonylurea drugs, useful for control of diabetes mellitus type two and it may exert anti inflammatory activity, by induction of nitric oxide production or through selective suppression of the cyclooxygenase pathway. Repaglinide is a new hypoglycemic agent, and a member of the carbamoylmethyl benzoic acid family. Some results from the literature demonstrate that repaglinide has favorable effects on the parameters of antioxidative balance. The objective of the present study was to assess the effect of glimepiride and repaglinide on atherosclerosis via interfering with the inflammatory and oxidative pathways. Twenty four local domestic male rabbits were involved in this study. The animals were randomly divided into four groups; Group I rabbits fed normal chow (oxiod) diet for 10 weeks. Group II rabbits were fed with 1% cholesterol enriched diet. Group III rabbits were fed with 1% cholesterol enriched diet together with Glimepiride (0.1 mg/kg once daily before morning feed). Group IV rabbits were fed with 1% cholesterol enriched diet together with Repaglinide (0.3 mg/kg once daily before morning feed). Blood samples were collected before (0 time) and every two weeks of experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), High-density lipoprotein cholesterol (HDL-C), high sensitive C - reactive protein (hsCRP), Interleukin - 6 (IL-6) and Tumor Necrosis Factor alpha (TNF-α) levels. At the end of 10 weeks, the aorta was removed for measurement of aortic Malondialdehyde (MDA), reduced glutathione (GSH) and aortic intimal thickness. Glimepiride and repaglinide treatment did show significant effect on lipid parameters compared with induced untreated group (P < 0.05). Also, they significantly reduced the elevation in hsCRP, IL-6, TNF-α, aortic MDA and aortic intimal thickness compared with induced untreated group (P < 0.05), and they helped to restore the aortic GSH levels (P < 0.05). Glimepiride and repaglinide may reduce atherosclerosis progression in hypercholesterolemic rabbits by interfering with the inflammatory and oxidative pathways without affecting lipid parameters.

Stochastic modelling of wall stresses in abdominal aortic aneurysms treated by a gene therapy.

PubMed

Mohand-Kaci, Faïza; Ouni, Anissa Eddhahak; Dai, Jianping; Allaire, Eric; Zidi, Mustapha

2012-01-01

A stochastic mechanical model using the membrane theory was used to simulate the in vivo mechanical behaviour of abdominal aortic aneurysms (AAAs) in order to compute the wall stresses after stabilisation by gene therapy. For that, both length and diameter of AAAs rats were measured during their expansion. Four groups of animals, control and treated by an endovascular gene therapy during 3 or 28 days were included. The mechanical problem was solved analytically using the geometric parameters and assuming the shape of aneurysms by a 'parabolic-exponential curve'. When compared to controls, stress variations in the wall of AAAs for treated arteries during 28 days decreased, while they were nearly constant at day 3. The measured geometric parameters of AAAs were then investigated using probability density functions (pdf) attributed to every random variable. Different trials were useful to define a reliable confidence region in which the probability to have a realisation is equal to 99%. The results demonstrated that the error in the estimation of the stresses can be greater than 28% when parameters uncertainties are not considered in the modelling. The relevance of the proposed approach for the study of AAA growth may be studied further and extended to other treatments aimed at stabilisation AAAs, using biotherapies and pharmacological approaches.

An Experimental and Numerical Comparison of the Rupture Locations of an Abdominal Aortic Aneurysm

PubMed Central

Doyle, Barry J.; Corbett, Timothy J.; Callanan, Anthony; Walsh, Michael T.; Vorp, David A.; McGloughlin, Timothy M.

2009-01-01

Purpose: To identify the rupture locations of idealized physical models of abdominal aortic aneurysm (AAA) using an in-vitro setup and to compare the findings to those predicted numerically. Methods: Five idealized AAAs were manufactured using Sylgard 184 silicone rubber, which had been mechanically characterized from tensile tests, tear tests, and finite element analysis. The models were then inflated to the point of rupture and recorded using a high-speed camera. Numerical modeling attempted to confirm these rupture locations. Regional variations in wall thickness of the silicone models was also quantified and applied to numerical models. Results: Four of the 5 models tested ruptured at inflection points in the proximal and distal regions of the aneurysm sac and not at regions of maximum diameter. These findings agree with high stress regions computed numerically. Wall stress appears to be independent of wall thickness, with high stress occurring at regions of inflection regardless of wall thickness variations. Conclusion: According to these experimental and numerical findings, AAAs experience higher stresses at regions of inflection compared to regions of maximum diameter. Ruptures of the idealized silicone models occurred predominantly at the inflection points, as numerically predicted. Regions of inflection can be easily identified from basic 3-dimensional reconstruction; as ruptures appear to occur at inflection points, these findings may provide a useful insight into the clinical significance of inflection regions. This approach will be applied to patient-specific models in a future study. PMID:19642790

Intimal cushions and endothelial nuclear elongation around mouse aortic branches and their spatial correspondence with patterns of lipid deposition

PubMed Central

Bond, Andrew R.; Ni, Chih-Wen; Jo, Hanjoong

2010-01-01

Spatial variation in hemodynamic stresses acting on the arterial wall may explain the nonuniform distribution of atherosclerosis. In thoracic aortas of LDL receptor/apolipoprotein E double knockout mice, lesions develop preferentially around the entire circumference of intercostal branch ostia, regardless of age, with the highest prevalence occurring upstream. Additional chevron-shaped lesions occur further upstream of the ostia. This pattern differs from the age-related ones occurring in people and rabbits. In the present study, patterns of near-wall blood flow around intercostal ostia in wild-type mice were estimated from the morphology of endothelial nuclei, which were shown in vitro to elongate in response to elevated shear stress and to align with the flow, and wall structure was assessed from confocal and scanning electron microscopy. A triangular intimal cushion surrounded the upstream part of most ostia. Nuclear length-to-width ratios were lowest over this cushion and highest at the sides of branches, regardless of age. Nuclear orientations were consistent with flow diverging around the branch. The pattern of nuclear morphology differed from the age-related ones observed in rabbits. The intimal cushion and the distribution of shear stress inferred from these observations can partly account for the pattern of lesions observed in knockout mice. Nuclear elongation in nonbranch regions was approximately constant across animals of different size, demonstrating the existence of a mechanism by which endothelial cells compensate for the dependence of mean aortic wall shear stress on body mass. PMID:19933414

Histopathological analysis of cellular localization of cathepsins in abdominal aortic aneurysm wall.

PubMed

Lohoefer, Fabian; Reeps, Christian; Lipp, Christina; Rudelius, Martina; Zimmermann, Alexander; Ockert, Stefan; Eckstein, Hans-Henning; Pelisek, Jaroslav

2012-08-01

An important feature of abdominal aortic aneurysm (AAA) is the destruction of vessel wall, especially elastin and collagen. Besides matrix metalloproteinases, cathepsins are the most potent elastolytic enzymes. The expression of cathepsins with known elastolytic and collagenolytic activities in the individual cells within AAA has not yet been determined. The vessel wall of 32 AAA patients and 10 organ donors was analysed by immunohistochemistry for expression of cathepsins B, D, K, L and S, and cystatin C in all cells localized within AAA. Luminal endothelial cells (ECs) of AAA were positive for cathepsin D and partially for cathepsins B, K and S. Endothelial cells of the neovessels and smooth muscle cells in the media were positive for all cathepsins tested, especially for cathepsin B. In the inflammatory infiltrate all cathepsins were expressed in the following pattern: B > D = S > K = L. Macrophages showed the highest staining intensity for all cathepsins. Furthermore, weak overall expression of cystatin C was observed in all the cells localized in the AAA with the exception of the ECs. There is markedly increased expression of the various cathepsins within the AAA wall compared to healthy aorta. Our data are broadly consistent with a role for cathepsins in AAA; and demonstrate expression of cathepsins D, B and S in phagocytic cells in the inflammatory infiltrate; and also may reveal a role for cathepsin B in lymphocytes. © 2012 The Authors. International Journal of Experimental Pathology © 2012 International Journal of Experimental Pathology.

Predictor of left ventricular dysfunction after aortic valve replacement in mixed aortic valve disease.

PubMed

Egbe, Alexander C; Warnes, Carole A

2017-02-01

The fate of the left ventricle (LV) after aortic valve replacement (AVR) in mixed aortic valve disease (MAVD) is unknown. Patients with moderate-severe MAVD, ejection fraction ≥50%, and no coronary artery disease who underwent AVR were identified. Moderate-severe MAVD was defined as a combination of ≥moderate aortic stenosis and ≥moderate aortic regurgitation. Assessment for LVD was performed at 1 and 5years after AVR. The purpose of the study was to determine prevalence and predictors of early and late left ventricular dysfunction (LVD) defined as ejection fraction <50% at 1 and 5years post-AVR. The severity of LV hypertrophy was assessed using LV mass index (LVMI), while relative wall thickness (RWT) was used to determine the type of hypertrophy. RWT was calculated as (2×posterior wall thickness)/LV end-diastolic dimension (LVEDD). A RWT score ≥0.42 and <0.42 indicates concentric and eccentric hypertrophy respectively. Patients with MAVD (n=179); age 63±8years, males 134 (75%); underwent AVR at Mayo Clinic, 1994-2010. Early LVD occurred in 38(21%). Predictors of early LVD were LVMI/LVEDD >3.1 (HR 1.83, CI 1.59-1.98); RWT >0.46 (HR 2.16, CI 1.21-4.99); and older age (HR 1.62, CI 1.23-3.02). Assessment of LV function was performed in 124 patients at 5-years post-AVR, and late LVD was present in 29(23%). Predictors of late LVD were LVMI/LVEDD >3.1 (HR 1.77, CI 1.24-2.01) and RWT >0.46 (HR 1.65, CI 1.29-2.24). All-cause mortality occurred in 21(12%), and was more common in patients with LVMI/LVEDD >3.1 (P=0.043) and RWT >0.46 (P=0.029). Patients with postoperative LVD showed less regression of LV mass after AVR even after controlling for blood pressure. LVD can occur after AVR even in the setting of normal preoperative LV function and absence of coronary artery disease. Preoperative LV mass was predictive of LVD and should be taken into consideration when determining the timing of AVR. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Interleukin-6 downregulated vascular smooth muscle cell contractile proteins via ATG4B-mediated autophagy in thoracic aortic dissection.

PubMed

An, Zhao; Qiao, Fan; Lu, Qijue; Ma, Ye; Liu, Yang; Lu, Fanglin; Xu, Zhiyun

2017-12-01

Interleukin-6 (IL-6) overexpression played an important role in the pathogenesis of thoracic aortic dissection (TAD). Our previous study found enhanced autophagy accompanying with contractile proteins α smooth muscle actin (α-SMA) and smooth muscle 22α (SM22α) degradation in TAD aortic vascular smooth muscle cells (VSMCs). Autophagy is an important way for intracellular proteins degradation, while IL-6 has been found as a contributing factor of autophagy in some cancers. These indicated IL-6 might contribute to the occurrence of TAD by promoting autophagy-induced contractile proteins degradation, which has not been investigated. The aim of the present study is to verify this hypothesis and investigate the mechanism of it. We collected 10 TAD and 10 control aortic specimens from patients underwent TAD surgical repair and coronary artery bypass grafting, respectively. Quantitative real-time polymerase chain reaction was used to detect mRNA expression. Protein expression level was assessed by enzyme-linked immunosorbent assay, western blot, and immunohistochemistry. Microtubule-associated protein 1 light chain 3 beta overexpression adenovirus with green and red fluorescent protein tags and transmission electron microscopy were used to detect autophagy level in VSMCs. 3-Methyladenine (3-MA) and chloroquine were used to block autophagy in human VSMCs. Experiment results showed that the expression of IL-6 was significantly increased accompanying with up-regulated autophagy in TAD aortic wall compared with controls. In vitro results showed that IL-6 stimulation decreased the expression of VSMCs contractile proteins α-SMA and SM22α accompanying with up-regulated autophagy. Blocking autophagy with 3-MA or chloroquine inhibited IL-6 induced α-SMA and SM22α degradation. Further investigation showed that autophagy-related 4B cysteine peptidase (ATG4B) was significantly overexpressed in TAD aortic wall and played important role in IL-6 induced autophagy up-regulation. ATG4B knockdown blocked IL-6-induced autophagy and α-SMA and SM22α degradation, while ATG4B overexpression partly replaced the function of IL-6 in human VSMCs. In conclusion, our study demonstrated that IL-6 downregulated expression of VSMCs contractile proteins α-SMA and SM22α via enhancing ATG4B-mediated autophagy in TAD.

Modification of Aortic Cannula With an Inlet Chamber to Induce Spiral Flow and Improve Outlet Flow.

PubMed

Darlis, Nofrizalidris; Osman, Kahar; Padzillah, Muhamad Hasbullah; Dillon, Jeswant; Md Khudzari, Ahmad Zahran

2018-05-01

Physiologically, blood ejected from the left ventricle in systole exhibited spiral flow characteristics. This spiral flow has been proven to have several advantages such as lateral reduction of directed forces and thrombus formation, while it also appears to be clinically beneficial in suppressing neurological complications. In order to deliver spiral flow characteristics during cardiopulmonary bypass operation, several modifications have been made on an aortic cannula either at the internal or at the outflow tip; these modifications have proven to yield better hemodynamic performances compared to standard cannula. However, there is no modification done at the inlet part of the aortic cannula for inducing spiral flow so far. This study was carried out by attaching a spiral inducer at the inlet of an aortic cannula. Then, the hemodynamic performances of the new cannula were compared with the standard straight tip end-hole cannula. This is achieved by modeling the cannula and attaching the cannula at a patient-specific aorta model. Numerical approach was utilized to evaluate the hemodynamic performance, and a water jet impact experiment was used to demonstrate the jet force generated by the cannula. The new spiral flow aortic cannula has shown some improvements by reducing approximately 21% of impinging velocity near to the aortic wall, and more than 58% reduction on total force generated as compared to standard cannula. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Aging impairs smooth muscle-mediated regulation of aortic stiffness: a defect in shock absorption function?

PubMed Central

Gao, Yuan Z.; Saphirstein, Robert J.; Yamin, Rina; Suki, Bela

2014-01-01

Increased aortic stiffness is an early and independent biomarker of cardiovascular disease. Here we tested the hypothesis that vascular smooth muscle cells (VSMCs) contribute significantly to aortic stiffness and investigated the mechanisms involved. The relative contributions of VSMCs, focal adhesions (FAs), and matrix to stiffness in mouse aorta preparations at optimal length and with confirmed VSMC viability were separated by the use of small-molecule inhibitors and activators. Using biomechanical methods designed for minimal perturbation of cellular function, we directly quantified changes with aging in aortic material stiffness. An alpha adrenoceptor agonist, in the presence of NG-nitro-l-arginine methyl ester (l-NAME) to remove interference of endothelial nitric oxide, increases stiffness by 90–200% from baseline in both young and old mice. Interestingly, increases are robustly suppressed by the Src kinase inhibitor PP2 in young but not old mice. Phosphotyrosine screening revealed, with aging, a biochemical signature of markedly impaired agonist-induced FA remodeling previously associated with Src signaling. Protein expression measurement confirmed a decrease in Src expression with aging. Thus we report here an additive model for the in vitro biomechanical components of the mouse aortic wall in which 1) VSMCs are a surprisingly large component of aortic stiffness at physiological lengths and 2) regulation of the VSMC component through FA signaling and hence plasticity is impaired with aging, diminishing the aorta's normal shock absorption function in response to stressors. PMID:25128168

Left ventricular hypertrophy induced by abdominal aortic banding and its prevention by angiotensin receptor blocker telmisartan--a proteomic analysis.

PubMed

Liu, Li; Wang, Wen; Meng, Xianmin; Gao, Jiuming; Wu, Haiying; Wang, Peihe; Wu, Weichun; Wang, Linlin; Ma, Liyuan; Zhang, Weiguo

2010-12-01

Cardiac hypertrophy is frequently caused by pressure overload (i.e., high blood pressure or hypertension) and can lead to heart failure. The major objective of the present study was to investigate the proteomic changes in response to the development of left ventricular hypertrophy (LVH) induced by abdominal aortic banding (AB) and its prevention by antihypertensive treatment with angiotensin II receptor blocker (ARB) telmisartan. One week after AB and Sham surgery, rats were assigned into three groups: SHAM-control, aortic banding without treatment (AB-Ctrl) and aortic banding with telmisartan treatment (AB-Telmi; 5mg/kg/day for 8 weeks). Echocardiography, hemodynamics, and pathology were performed to assess LVH. Left ventricular myocardium was sampled. The analysis of proteomic proteins from myocardium was performed by two-dimensional gel electrophoresis and MALDI-TOF-MS. In AB-Ctrl, heart rate, systolic arterial blood pressure, diastolic blood pressure, left ventricular end systolic pressure, interventricular septal thickness at diastole, posterior wall thickness in diastole, heart weight (HW) and HW/body weight (BW) were increased, indicating that both hypertension and LVH developed. Telmisartan prevented hypertension and LVH. Concurrently, among numerous proteins, there were 17 that were differentially expressed among hypertrophic hearts, normal hearts, and the hearts where hypertrophic response was suppressed by ARB treatment. Primarily, proteins involved in cell structure, metabolism, stress and signal transduction exhibited up-regulations in LVH, providing cellular and molecular mechanism for hypertrophic development. These changes were prevented or greatly attenuated by telmisartan regimen. Interestingly, antioxidative-related heat shock protein 2 was detected neither in SHAM-Ctrl nor in AB-Ctrl, but in AB-Telmi. LVH is accompanied by series changes of protein expression. Both LVH and proteomic changes can be prevented by blockade of renin-angiotensin system with telmisartan. These protein alterations may constitute mechanistic pathways leading to hypertrophy development and experimental targets for novel therapeutic strategy.

Measurements of Intra-Aortic Balloon Wall Movement During Inflation and Deflation: Effects of Angulation.

PubMed

Bruti, Gianpaolo; Kolyva, Christina; Pepper, John R; Khir, Ashraf W

2015-08-01

The intra-aortic balloon pump (IABP) is a ventricular assist device that is used with a broad range of pre-, intra-, and postoperative patients undergoing cardiac surgery. Although the clinical efficacy of the IABP is well documented, the question of reduced efficacy when patients are nursed in the semi-recumbent position remains outstanding. The aim of the present work is therefore to investigate the underlying mechanics responsible for the loss of IABP performance when operated at an angle to the horizontal. Simultaneous recordings of balloon wall movement, providing an estimate of its diameter (D), and fluid pressure were taken at three sites along the intra-aortic balloon (IAB) at 0 and 45°. Flow rate, used for the calculation of displaced volume, was also recorded distal to the tip of the balloon. An in vitro experimental setup was used, featuring physiological impedances on either side of the IAB ends. IAB inflation at an angle of 45° showed that D increases at the tip of the IAB first, presenting a resistance to the flow displaced away from the tip of the balloon. The duration of inflation decreased by 15.5%, the inflation pressure pulse decreased by 9.6%, and volume decreased by 2.5%. Similarly, changing the position of the balloon from 0 to 45°, the balloon deflation became slower by 35%, deflation pressure pulse decreased by 14.7%, and volume suctioned was decreased by 15.2%. IAB wall movement showed that operating at 45° results in slower deflation compared with 0°. Slow wall movement, and changes in inflation and deflation onsets, result in a decreased volume displacement and pressure pulse generation. Operating the balloon at an angle to the horizontal, which is the preferred nursing position in intensive care units, results in reduced IAB inflation and deflation performance, possibly compromising its clinical benefits. Copyright © 2015 The Authors. Artificial Organs published by Wiley Periodicals, Inc. on behalf of International Center for Artificial Organ and Transplantation (ICAOT).

Flow stagnation volume and abdominal aortic aneurysm growth: Insights from patient-specific computational flow dynamics of Lagrangian-coherent structures.

PubMed

Joly, Florian; Soulez, Gilles; Garcia, Damien; Lessard, Simon; Kauffmann, Claude

2018-01-01

Abdominal aortic aneurysms (AAA) are localized, commonly-occurring dilations of the aorta. When equilibrium between blood pressure (loading) and wall mechanical resistance is lost, rupture ensues, and patient death follows, if not treated immediately. Experimental and numerical analyses of flow patterns in arteries show direct correlations between wall shear stress and wall mechano-adaptation with the development of zones prone to thrombus formation. For further insights into AAA flow topology/growth interaction, a workout of patient-specific computational flow dynamics (CFD) is proposed to compute finite-time Lyapunov exponents and extract Lagrangian-coherent structures (LCS). This computational model was first compared with 4-D phase-contrast magnetic resonance imaging (MRI) in 5 patients. To better understand the impact of flow topology and transport on AAA growth, hyperbolic, repelling LCS were computed in 1 patient during 8-year follow-up, including 9 volumetric morphologic AAA measures by computed tomography-angiography (CTA). LCS defined barriers to Lagrangian jet cores entering AAA. Domains enclosed between LCS and the aortic wall were considered to be stagnation zones. Their evolution was studied during AAA growth. Good correlation - 2-D cross-correlation coefficients of 0.65, 0.86 and 0.082 (min, max, SD) - was obtained between numerical simulations and 4-D MRI acquisitions in 6 specific cross-sections from 4 patients. In follow-up study, LCS divided AAA lumens into 3 dynamically-isolated zones: 2 stagnation volumes lying in dilated portions of the AAA, and circulating volume connecting the inlet to the outlet. The volume of each zone was tracked over time. Although circulating volume remained unchanged during 8-year follow-up, the AAA lumen and main stagnation zones grew significantly (8 cm 3 /year and 6 cm 3 /year, respectively). This study reveals that transient transport topology can be quantified in patient-specific AAA during disease progression by CTA, in parallel with lumen morphology. It is anticipated that analysis of the main AAA stagnation zones by patient-specific CFD on a yearly basis could help to predict AAA growth and rupture. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Evaluation of the invasion of esophageal cancer to the aorta by cine-MR imaging].

PubMed

Kawahara, I; Nishimura, H; Uchida, M; Ueda, H; Fujimoto, K; Meno, S; Hayabuchi, N; Fujita, H

1993-01-25

We examined the usefulness of cine-MR imaging for evaluation of the invasion of esophageal cancer to the aorta in 12 cases. We used the technique of field echo pulse sequence. When the low intensity stripe was recognized between the tumor and the wall of aorta, we interpreted it as negative finding of the direct tumor invasion. By using this criteria, 11 of the 12 cases (92%) of the esophageal cancer for aortic wall invasion were correctly diagnosed as compared with 75% correct diagnosis by conventional MR imaging.

Advanced atherosclerosis is associated with increased medial degeneration in sporadic ascending aortic aneurysms.

PubMed

Albini, Paul T; Segura, Ana Maria; Liu, Guanghui; Minard, Charles G; Coselli, Joseph S; Milewicz, Dianna M; Shen, Ying H; LeMaire, Scott A

2014-02-01

The pathogenesis of non-familial, sporadic ascending aortic aneurysms (SAAA) is poorly understood, and the relationship between ascending aortic atherosclerosis and medial degeneration is unclear. We evaluated the prevalence and severity of aortic atherosclerosis and its association with medial degeneration in SAAA. Atherosclerosis was characterized in ascending aortic tissues collected from 68 SAAA patients (mean age, 62.9 ± 12.0 years) and 15 controls (mean age, 56.6 ± 11.4 years [P = 0.07]) by using a modified American Heart Association classification system. Upon histologic examination, 97% of SAAA patients and 73% of controls showed atherosclerotic changes. Most SAAA samples had intermediate (types 2 and 3, 35%) or advanced atherosclerosis (types ≥ 4; 40%), whereas most control samples showed minimal atherosclerosis (none or type 1, 80%; P < 0.001 after adjusting for age). In a separate analysis, we examined the total incidence and grade distribution of medial degenerative changes among SAAA samples according to atherosclerosis grade. Advanced atherosclerosis was associated with higher grades of smooth muscle cell depletion (P < 0.001), elastic fiber depletion (P = 0.02), elastic fiber fragmentation (P < 0.001), and mucopolysaccharide accumulation (P = 0.04). Aortic diameter was larger in SAAA patients with advanced atherosclerosis than in patients with minimal (P = 0.04) or intermediate atherosclerosis (P = 0.04). Immunostaining showed marked CD3+ T-cell and CD68+ macrophage infiltration, MMP-2 and MMP-9 production, and cryopyrin expression in the medial layer adjacent to atherosclerotic plaque. SAAA tissues exhibited advanced atherosclerosis that was associated with severe medial degeneration and increased aortic diameter. Our findings suggest a role for atherosclerosis in the progression of sporadic ascending aortic aneurysms. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Ablation of Potassium-Chloride Cotransporter Type 3 (Kcc3) in Mouse Causes Multiple Cardiovascular Defects and Isosmotic Polyuria.

PubMed

Garneau, Alexandre P; Marcoux, Andrée-Anne; Noël, Micheline; Frenette-Cotton, Rachelle; Drolet, Marie-Claude; Couet, Jacques; Larivière, Richard; Isenring, Paul

2016-01-01

Inactivation of Kcc3 in a mixed 129/Sv×C57BL/6 mouse background has been previously found to increase systemic blood pressure (BP) through presumed neurogenic mechanisms. Yet, while this background is generally not considered ideal to investigate the cardiovascular system, KCC3 is also expressed in the arterial wall and proximal nephron. In the current study, the effects of Kcc3 ablation was investigated in a pure rather than mixed C57BL/6J background under regular- and high-salt diets to determine whether they could be mediated through vasculogenic and nephrogenic mechanisms. Aortas were also assessed for reactivity to pharmacological agents while isolated from the influence of sympathetic ganglia. This approach led to the identification of unforeseen abnormalities such as lower pulse pressure, heart rate, aortic reactivity and aortic wall thickness, but higher diastolic BP, left ventricular mass and urinary output in the absence of increased catecholamine levels. Salt loading also led systolic BP to be higher, but to no further changes in hemodynamic parameters. Importantly, aortic vascular smooth muscle cells and cardiomyocytes were both found to express KCC3 abundantly in heterozygous mice. Hence, Kcc3 inactivation in our model caused systemic vascular resistance and ventricular mass to increase while preventing extracellular fluid volume to accumulate. Given that it also affected the physiological properties of aortas in vitro, vasculogenic mechanisms could therefore account for a number of the hemodynamic abnormalities observed.

Uncertainty Quantification applied to flow simulations in thoracic aortic aneurysms

NASA Astrophysics Data System (ADS)

Boccadifuoco, Alessandro; Mariotti, Alessandro; Celi, Simona; Martini, Nicola; Salvetti, Maria Vittoria

2015-11-01

The thoracic aortic aneurysm is a progressive dilatation of the thoracic aorta causing a weakness in the aortic wall, which may eventually cause life-threatening events. Clinical decisions on treatment strategies are currently based on empiric criteria, like the aortic diameter value or its growth rate. Numerical simulations can give the quantification of important indexes which are impossible to be obtained through in-vivo measurements and can provide supplementary information. Hemodynamic simulations are carried out by using the open-source tool SimVascular and considering patient-specific geometries. One of the main issues in these simulations is the choice of suitable boundary conditions, modeling the organs and vessels not included in the computational domain. The current practice is to use outflow conditions based on resistance and capacitance, whose values are tuned to obtain a physiological behavior of the patient pressure. However it is not known a priori how this choice affects the results of the simulation. The impact of the uncertainties in these outflow parameters is investigated here by using the generalized Polynomial Chaos approach. This analysis also permits to calibrate the outflow-boundary parameters when patient-specific in-vivo data are available.

Effect of preoperative antiplatelet drugs on vascular prostacyclin synthesis.

PubMed

Karwande, S V; Weksler, B B; Gay, W A; Subramanian, V A

1987-03-01

Patients undergoing aortocoronary bypass using autogenous saphenous veins were randomly divided into three comparable groups. Group 1 (n = 10) acted as a control, Group 2 (n = 14) received 80 mg of aspirin at midnight before the operation, and Group 3 (n = 12) received 80 mg of aspirin and 75 mg of dipyridamole at midnight and an additional 75-mg dose of dipyridamole at 6 AM. The purpose was to determine which regimen would maximally inhibit platelet function without depressing vascular prostacyclin synthesis. Serum thromboxane A2, saphenous vein wall and aortic wall prostacyclin, platelet aggregation, and bleeding time were measured in all patients. None was restarted on a regimen of aspirin or dipyridamole postoperatively. Aspirin alone and in combination with dipyridamole significantly inhibited thromboxane A2 and platelet aggregation in all treated patients but spared venous prostacyclin synthesis. Aortic prostacyclin synthesis was partially inhibited in both treated groups. Chest tube drainage was comparable in all three groups. These results indicate that the combination of aspirin and dipyridamole offers no measurable advantage over aspirin alone in the perioperative period.

The efficacy and tolerability of azilsartan in obese insulin-resistant mice with left ventricular pressure overload.

PubMed

Tarikuz Zaman, A K M; McLean, Danielle L; Sobel, Burton E

2013-10-01

Angiotensin II receptor blockers (ARBs) are used widely for the treatment of heart failure. However, their use in obese and insulin-resistant patients remains controversial. To clarify their potential efficacy in these conditions, we administered azilsartan medoxomil (azilsartan), a prodrug of an angiotensin II receptor blocker to mice fed a high-fat diet (HFD) with left ventricular (LV) pressure overload (aortic banding). LV fibrosis (hydroxyproline), cardiac plasminogen activator inhibitor-1 (PAI-1; a marker of profibrosis), and creatine kinase (a marker of myocardial viability and energetics) were assessed. LV wall thickness and cardiac function were assessed echocardiographically. Mice given a HFD were obese and insulin resistant. Their LV hypertrophy was accompanied by greater LV PAI-1 and reduced LV creatine kinase compared with normal diet controls. Drug treatment reduced LV wall thickness, hypertrophy, and PAI-1 and increased cardiac output after aortic banding compared with results in HFD vehicle controls. Thus, azilsartan exerted favorable biological effects on the hearts of obese insulin-resistant mice subjected to LV pressure overload consistent with its potential utility in patients with analogous conditions.

Resveratrol prevents high fat/sucrose diet-induced central arterial wall inflammation and stiffening in nonhuman primates

PubMed Central

Mattison, Julie A.; Wang, Mingyi; Bernier, Michel; Zhang, Jing; Park, Sung-Soo; Maudsley, Stuart; An, Steven S.; Santhanam, Lakshmi; Martin, Bronwen; Faulkner, Shakeela; Morrell, Christopher; Baur, Joseph A.; Peshkin, Leonid; Sosnowska, Danuta; Csiszar, Anna; Herbert, Richard L.; Tilmont, Edward M.; Ungvari, Zoltan; Pearson, Kevin J.; Lakatta, Edward G.; de Cabo, Rafael

2014-01-01

SUMMARY Central arterial wall stiffening driven by a chronic inflammatory milieu accompanies arterial diseases, the leading cause of cardiovascular (CV) morbidity and mortality in Western society. Increase in central arterial wall stiffening, measured as an increase in aortic pulse wave velocity (PWV), is a major risk factor for clinical CV disease events. However, no specific therapies to reduce PWV are presently available. In rhesus monkeys, a two-year diet high in fat and sucrose (HFS) increases not only body weight and cholesterol, but also induces prominent central arterial wall stiffening and increases PWV and inflammation. The observed loss of endothelial cell integrity, lipid and macrophage infiltration, and calcification of the arterial wall were driven by genomic and proteomic signatures of oxidative stress and inflammation. Resveratrol prevented the HFS-induced arterial wall inflammation and the accompanying increase in PWV. Dietary resveratrol may hold promise as a novel therapy to ameliorate increases in PWV. PMID:24882067

Resveratrol prevents high fat/sucrose diet-induced central arterial wall inflammation and stiffening in nonhuman primates.

PubMed

Mattison, Julie A; Wang, Mingyi; Bernier, Michel; Zhang, Jing; Park, Sung-Soo; Maudsley, Stuart; An, Steven S; Santhanam, Lakshmi; Martin, Bronwen; Faulkner, Shakeela; Morrell, Christopher; Baur, Joseph A; Peshkin, Leonid; Sosnowska, Danuta; Csiszar, Anna; Herbert, Richard L; Tilmont, Edward M; Ungvari, Zoltan; Pearson, Kevin J; Lakatta, Edward G; de Cabo, Rafael

2014-07-01

Central arterial wall stiffening, driven by a chronic inflammatory milieu, accompanies arterial diseases, the leading cause of cardiovascular (CV) morbidity and mortality in Western society. An increase in central arterial wall stiffening, measured as an increase in aortic pulse wave velocity (PWV), is a major risk factor for clinical CV disease events. However, no specific therapies to reduce PWV are presently available. In rhesus monkeys, a 2 year diet high in fat and sucrose (HFS) increases not only body weight and cholesterol, but also induces prominent central arterial wall stiffening and increases PWV and inflammation. The observed loss of endothelial cell integrity, lipid and macrophage infiltration, and calcification of the arterial wall were driven by genomic and proteomic signatures of oxidative stress and inflammation. Resveratrol prevented the HFS-induced arterial wall inflammation and the accompanying increase in PWV. Dietary resveratrol may hold promise as a therapy to ameliorate increases in PWV. Copyright © 2014 Elsevier Inc. All rights reserved.

Augmented vascular smooth muscle cell stiffness and adhesion when hypertension is superimposed on aging.

PubMed

Sehgel, Nancy L; Sun, Zhe; Hong, Zhongkui; Hunter, William C; Hill, Michael A; Vatner, Dorothy E; Vatner, Stephen F; Meininger, Gerald A

2015-02-01

Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most previous studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter the mechanical properties of the vascular wall. Alternatively, we hypothesized that a significant component of increased vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of vascular smooth muscle cells, and that aging would augment the contribution from vascular smooth muscle cells when compared with the extracellular matrix. Accordingly, we studied aortic stiffness in young (16-week-old) and old (64-week-old) spontaneously hypertensive rats and Wistar-Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats when compared with young Wistar-Kyoto rats, and these continued to rise in old spontaneously hypertensive rats when compared with age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats versus Wistar-Kyoto rats. were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both vascular smooth muscle cell stiffness and vascular smooth muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. These findings support the concept that stiffness and adhesive properties of vascular smooth muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging. © 2014 American Heart Association, Inc.

[Aortic valve insufficiency due to rupture of the cusp in a patient with multiple trauma].

PubMed

Vidmar, J; Brilej, D; Voga, G; Kovacic, N; Smrkolj, V

2003-06-01

Lesions of the heart valve caused by blunt chest trauma is rare, but when it does occur it can significantly injure the patient. On the basis of autopsy studies, research shows that heart valves are injured in less than 5% of patients who have died due to impact thoracic trauma. Among the heart valves, the aortic valve is the most often lacerated, which has been proved by relevant autopsy and clinical studies. Aortic valve lesions can be the only injury, but it is possible that additional heart or large vessel injuries are also present (myocardial contusion, rupture of the atrial septum, aortic rupture, rupture of the left common carotid artery). The force that causes such an injury is often great and often causes injuries to other organs and organ systems. In a multiple trauma patient, it is very important to specifically look for heart-related injuries because it is possible that they may be overlooked or missed by the surgeon, because of other obvious injuries. We describe the case of a 41-year-old man with multiple trauma who was diagnosed with aortic valve insufficiency due to rupture of the left coronary cusp 6 weeks after a road accident. Valvuloplasty was performed. Seven years later the patient is free of symptoms and is in good physical condition. Echocardiography showed normal dimensions of the heart chambers, a normal thickness of the heart walls, and normal systolic and diastolic function of the left ventricle. Heart valves are morphologically normal, and only an unimportant aortic insufficiency was noticed by echocardiography.

Ameliorative role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats.

PubMed

Singh, Amrit Pal; Singh, Randhir; Krishan, Pawan

2015-04-01

Fibrates are peroxisome proliferator-activated receptor-α agonists and are clinically used for treatment of dyslipidemia and hypertriglyceridemia. Fenofibrate is reported as a cardioprotective agent in various models of cardiac dysfunction; however, limited literature is available regarding the role of gemfibrozil as a possible cardioprotective agent, especially in a non-obese model of cardiac remodelling. The present study investigated the role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats. Cardiac hypertrophy was induced by partial abdominal aortic constriction in rats and they survived for 4 weeks. The cardiac hypertrophy was assessed by measuring left ventricular weight to body weight ratio, left ventricular wall thickness, and protein and collagen content. The oxidative stress in the cardiac tissues was assessed by measuring thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The haematoxylin-eosin and picrosirius red staining was used to observe cardiomyocyte diameter and collagen deposition, respectively. Moreover, serum levels of cholesterol, high-density lipoproteins, triglycerides, and glucose were also measured. Gemfibrozil (30 mg/kg, p.o.) was administered since the first day of partial abdominal aortic constriction and continued for 4 weeks. The partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy are indicated by significant change in various parameters used in the present study that were ameliorated with gemfibrozil treatment in rats. No significant change in serum parameters was observed between various groups used in the present study. It is concluded that gemfibrozil ameliorates partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy and in rats.

In vivo geometry of the kissing stent and covered endovascular reconstruction of the aortic bifurcation configurations in aortoiliac occlusive disease

PubMed Central

Ter Mors, Thijs G; Slump, Cornelis H; Geelkerken, Robert H; Holewijn, Suzanne; Reijnen, Michel MPJ

2017-01-01

Objectives Various configurations of kissing stent (KS) configurations exist and patency rates vary. In response the covered endovascular reconstruction of the aortic bifurcation configuration was designed to minimize mismatch and improve outcome. The aim of the current study is to compare geometrical mismatch of kissing stent with the covered endovascular reconstruction of the aortic bifurcation configuration in vivo. Methods Post-operative computed tomographic data and patient demographics from 11 covered endovascular reconstruction of the aortic bifurcation and 11 matched kissing stent patients were included. A free hand region of interest and ellipse fitting method were applied to determine mismatch areas and volumes. Conformation of the stents to the vessel wall was expressed using the D-ratio. Results Patients were mostly treated for Rutherford category 2 and 3 (64%) with a lesion classification of TASC C and D in 82%. Radial mismatch area and volume for the covered endovascular reconstruction of the aortic bifurcation group was significantly lower compared to the kissing stent configuration (P < 0.05). The D-ratio did not significantly differ between groups. Measurements were performed with good intra-class correlation. There were no significant differences in the post-procedural aortoiliac anatomy. Conclusions The present study shows that radial mismatch exists in vivo and that large differences in mismatch exist, in favour of the covered endovascular reconstruction of the aortic bifurcation configuration. Future research should determine if the decreased radial mismatch results in improved local flow profiles and subsequent clinical outcome. PMID:28530484

In vivo geometry of the kissing stent and covered endovascular reconstruction of the aortic bifurcation configurations in aortoiliac occlusive disease.

PubMed

Groot Jebbink, Erik; Ter Mors, Thijs G; Slump, Cornelis H; Geelkerken, Robert H; Holewijn, Suzanne; Reijnen, Michel Mpj

2017-12-01

Objectives Various configurations of kissing stent (KS) configurations exist and patency rates vary. In response the covered endovascular reconstruction of the aortic bifurcation configuration was designed to minimize mismatch and improve outcome. The aim of the current study is to compare geometrical mismatch of kissing stent with the covered endovascular reconstruction of the aortic bifurcation configuration in vivo. Methods Post-operative computed tomographic data and patient demographics from 11 covered endovascular reconstruction of the aortic bifurcation and 11 matched kissing stent patients were included. A free hand region of interest and ellipse fitting method were applied to determine mismatch areas and volumes. Conformation of the stents to the vessel wall was expressed using the D-ratio. Results Patients were mostly treated for Rutherford category 2 and 3 (64%) with a lesion classification of TASC C and D in 82%. Radial mismatch area and volume for the covered endovascular reconstruction of the aortic bifurcation group was significantly lower compared to the kissing stent configuration ( P < 0.05). The D-ratio did not significantly differ between groups. Measurements were performed with good intra-class correlation. There were no significant differences in the post-procedural aortoiliac anatomy. Conclusions The present study shows that radial mismatch exists in vivo and that large differences in mismatch exist, in favour of the covered endovascular reconstruction of the aortic bifurcation configuration. Future research should determine if the decreased radial mismatch results in improved local flow profiles and subsequent clinical outcome.

Aortic flow patterns and wall shear stress maps by 4D-flow cardiovascular magnetic resonance in the assessment of aortic dilatation in bicuspid aortic valve disease.

PubMed

Rodríguez-Palomares, José Fernando; Dux-Santoy, Lydia; Guala, Andrea; Kale, Raquel; Maldonado, Giuliana; Teixidó-Turà, Gisela; Galian, Laura; Huguet, Marina; Valente, Filipa; Gutiérrez, Laura; González-Alujas, Teresa; Johnson, Kevin M; Wieben, Oliver; García-Dorado, David; Evangelista, Arturo

2018-04-26

In patients with bicuspid valve (BAV), ascending aorta (AAo) dilatation may be caused by altered flow patterns and wall shear stress (WSS). These differences may explain different aortic dilatation morphotypes. Using 4D-flow cardiovascular magnetic resonance (CMR), we aimed to analyze differences in flow patterns and regional axial and circumferential WSS maps between BAV phenotypes and their correlation with ascending aorta dilatation morphotype. One hundred and one BAV patients (aortic diameter ≤ 45 mm, no severe valvular disease) and 20 healthy subjects were studied by 4D-flow CMR. Peak velocity, flow jet angle, flow displacement, in-plane rotational flow (IRF) and systolic flow reversal ratio (SFRR) were assessed at different levels of the AAo. Peak-systolic axial and circumferential regional WSS maps were also estimated. Unadjusted and multivariable adjusted linear regression analyses were used to identify independent correlates of aortic root or ascending dilatation. Age, sex, valve morphotype, body surface area, flow derived variables and WSS components were included in the multivariable models. The AAo was non-dilated in 24 BAV patients and dilated in 77 (root morphotype in 11 and ascending in 66). BAV phenotype was right-left (RL-) in 78 patients and right-non-coronary (RN-) in 23. Both BAV phenotypes presented different outflow jet direction and velocity profiles that matched the location of maximum systolic axial WSS. RL-BAV velocity profiles and maximum axial WSS were homogeneously distributed right-anteriorly, however, RN-BAV showed higher variable profiles with a main proximal-posterior distribution shifting anteriorly at mid-distal AAo. Compared to controls, BAV patients presented similar WSS magnitude at proximal, mid and distal AAo (p = 0.764, 0.516 and 0.053, respectively) but lower axial and higher circumferential WSS components (p < 0.001 for both, at all aortic levels). Among BAV patients, RN-BAV presented higher IRF at all levels (p = 0.024 proximal, 0.046 mid and 0.002 distal AAo) and higher circumferential WSS at mid and distal AAo (p = 0.038 and 0.046, respectively) than RL-BAV. However, axial WSS was higher in RL-BAV compared to RN-BAV at proximal and mid AAo (p = 0.046, 0.019, respectively). Displacement and axial WSS were independently associated with the root-morphotype, and circumferential WSS and SFRR with the ascending-morphotype. Different BAV-phenotypes present different flow patterns with an anterior distribution in RL-BAV, whereas, RN-BAV patients present a predominant posterior outflow jet at the sinotubular junction that shifts to anterior or right anterior in mid and distal AAo. Thus, RL-BAV patients present a higher axial WSS at the aortic root while RN-BAV present a higher circumferential WSS in mid and distal AAo. These results may explain different AAo dilatation morphotypes in the BAV population.

Chronic Treatment with Minoxidil Induces Elastic Fiber Neosynthesis and Functional Improvement in the Aorta of Aged Mice.

PubMed

Coquand-Gandit, Marion; Jacob, Marie-Paule; Fhayli, Wassim; Romero, Beatriz; Georgieva, Miglena; Bouillot, Stéphanie; Estève, Eric; Andrieu, Jean-Pierre; Brasseur, Sandrine; Bouyon, Sophie; Garcia-Honduvilla, Natalio; Huber, Philippe; Buján, Julia; Atanasova, Milena; Faury, Gilles

2017-06-01

Normal arterial aging processes involve vascular cell dysfunction associated with wall stiffening, the latter being due to progressive elastin and elastic fiber degradation, and elastin and collagen cross-linking by advanced glycation end products (AGEs). These processes progressively lead to cardiovascular dysfunction during aging. Elastin is only synthesized during late gestation and childhood, and further degradation occurring throughout adulthood cannot be physiologically compensated by replacement of altered material. However, the ATP-dependent K + channel opener minoxidil has been shown to stimulate elastin expression in vitro and in vivo in the aorta of young adult rats. Therefore, we have studied the effect of a 10-week chronic oral treatment with minoxidil (120 mg/L in drinking water) on the aortic structure and function in aged 24-month-old mice. Minoxidil treatment increased tropoelastin, fibulin-5, and lysyl-oxidase messenger RNA levels, reinduced a moderate expression of elastin, and lowered the levels of AGE-related molecules. This was accompanied by the formation of newly synthesized elastic fibers, which had diverse orientations in the wall. A decrease in the glycation capacity of aortic elastin was also produced by minoxidil treatment. The ascending aorta also underwent a minoxidil-induced increase in diameter and decrease in wall thickness, which partly reversed the age-associated thickening and returned the wall thickness value and strain-stress relation closer to those of younger adult animals. In conclusion, our results suggest that minoxidil presents an interesting potential for arterial remodeling in an antiaging perspective, even when treating already aged animals.

Maternal obesity, gestational weight gain and childhood cardiac outcomes: role of childhood body mass index.

PubMed

Toemen, L; Gishti, O; van Osch-Gevers, L; Steegers, E A P; Helbing, W A; Felix, J F; Reiss, I K M; Duijts, L; Gaillard, R; Jaddoe, V W V

2016-07-01

Maternal obesity may affect cardiovascular outcomes in the offspring. We examined the associations of maternal prepregnancy body mass index and gestational weight gain with childhood cardiac outcomes and explored whether these associations were explained by parental characteristics, infant characteristics or childhood body mass index. In a population-based prospective cohort study among 4852 parents and their children, we obtained maternal weight before pregnancy and in early, mid- and late pregnancy. At age 6 years, we measured aortic root diameter (cm) and left ventricular dimensions. We calculated left ventricular mass (g), left ventricular mass index (g m(-2.7)), relative wall thickness ((2 × left ventricular posterior wall thickness)/left ventricular diameter), fractional shorting (%), eccentric left ventricular hypertrophy and concentric remodeling. A one standard deviation score (SDS) higher maternal prepregnancy body mass index was associated with higher left ventricular mass (0.10 SDS (95% confidence interval (CI) 0.08, 0.13)), left ventricular mass index (0.06 SDS (95% CI 0.03, 0.09)) and aortic root diameter (0.09 SDS (95% CI 0.06, 0.12)), but not with relative wall thickness or fractional shortening. A one SDS higher maternal prepregnancy body mass index was associated with an increased risk of eccentric left ventricular hypertrophy (odds ratio 1.21 (95% CI 1.03, 1.41)), but not of concentric remodeling. When analyzing the effects of maternal weight in different periods simultaneously, only maternal prepregnancy weight and early pregnancy weight were associated with left ventricular mass, left ventricular mass index and aortic root diameter (P-values<0.05), independent of weight in other pregnancy periods. All observed associations were independent of parental and infant characteristics, but attenuated to non-significance after adjustment for childhood body mass index. Maternal prepregnancy body mass index and weight gain in early pregnancy are both associated with offspring cardiac structure in childhood, but these associations seem to be fully explained by childhood body mass index.

Nucleotide Catabolism on the Surface of Aortic Valve Xenografts; Effects of Different Decellularization Strategies.

PubMed

Kutryb-Zajac, Barbara; Yuen, Ada H Y; Khalpey, Zain; Zukowska, Paulina; Slominska, Ewa M; Taylor, Patricia M; Goldstein, Steven; Heacox, Albert E; Lavitrano, Marialuisa; Chester, Adrian H; Yacoub, Magdi H; Smolenski, Ryszard T

2016-04-01

Extracellular nucleotide metabolism controls thrombosis and inflammation and may affect degeneration and calcification of aortic valve prostheses. We evaluated the effect of different decellularization strategies on enzyme activities involved in extracellular nucleotide metabolism. Porcine valves were tested intact or decellularized either by detergent treatment or hypotonic lysis and nuclease digestion. The rates of ATP hydrolysis, AMP hydrolysis, and adenosine deamination were estimated by incubation of aorta or valve leaflet sections with substrates followed by HPLC analysis. We demonstrated relatively high activities of ecto-enzymes on porcine valve as compared to the aortic wall. Hypotonic lysis/nuclease digestion preserved >80 % of ATP and AMP hydrolytic activity but reduced adenosine deamination to <10 %. Detergent decellularization completely removed (<5 %) all these activities. These results demonstrate high intensity of extracellular nucleotide metabolism on valve surface and indicate that various valve decellularization techniques differently affect ecto-enzyme activities that could be important in the development of improved valve prostheses.

Changes in turbulence with rotation of the omnicarbon prosthesis.

PubMed

Travis, Brandon R; Nyboe, Camilla; Christensen, Thomas D; Smerup, Morten; Johansen, Peter; Nygaard, Hans; Hasenkam, J Michael

2007-01-01

This study was performed to determine whether annular plane orientation of the Omnicarbon aortic valve influences forward flow turbulence. The Omnicarbon prostheses was modified to allow in situ manual rotation of the valve when implanted in the aortic position of eight 90 kg pigs. Pulsed Doppler ultrasound was used to acquire velocity measurements at 17 locations within the cross-sectional area of the ascending aorta. In each animal, 12 valve rotations were tested in this manner. Reynolds normal stresses were estimated from the velocity measurements. High Reynolds normal stresses were concentrated between left and posterior-right sides of the aortic wall for all orientations studied. No trends in mean or maximum Reynolds normal stresses with respect to valve rotation were consistent in the experiments. Unlike previous experiments with the Medtronic-Hall tilting disc valve, these experiments showed no notable changes in Reynolds normal stress with respect to orientation of the Omnicarbon valve. This suggests that the tendency of turbulent stresses to change with tilting disc valve orientation may be dependent on valve design.

Reproducibility of ECG-gated ultrasound diameter assessment of small abdominal aortic aneurysms.

PubMed

Bredahl, K; Eldrup, N; Meyer, C; Eiberg, J E; Sillesen, H

2013-03-01

No standardised ultrasound procedure to obtain reliable growth estimates for abdominal aortic aneurysms (AAA) is currently available. We investigated the feasibility and reproducibility of a novel approach controlling for a combination of vessel wall delineation and cardiac cycle variation. Prospective comparative study. Consecutive patients (N = 27) with an AAA, attending their 6-month control as part of a medical treatment trial, were scanned twice by two ultrasound operators. Then, all ultrasound recordings were transferred to a core facility and analysed by a third person. The AAA diameter was determined in four different ways: from the leading edge of adventitia on the anterior wall to either the leading edge of the adventitia (method A) or leading edge of the intima (method B) on the posterior wall, with both measurements performed in systole and diastole. Inter-operator reproducibility was ± 3 mm for all methods applied. There was no difference in outcome between methods A and B; likewise, end-diastolic measurement did not improve reproducibility in preference to peak-systolic measurement. The use of a standardised ultrasound protocol including ECG-gating and subsequent off-line reading with minute calliper placement reduces variability. This may be of use in developing protocols to better detect even small AAA growth rates during clinical trials. Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Athlete's Heart: Is the Morganroth Hypothesis Obsolete?

PubMed

Haykowsky, Mark J; Samuel, T Jake; Nelson, Michael D; La Gerche, Andre

2018-05-01

In 1975, Morganroth and colleagues reported that the increased left ventricular (LV) mass in highly trained endurance athletes versus nonathletes was primarily due to increased end-diastolic volume while the increased LV mass in resistance trained athletes was solely due to an increased LV wall thickness. Based on the divergent remodelling patterns observed, Morganroth and colleagues hypothesised that the increased "volume" load during endurance exercise may be similar to that which occurs in patients with mitral or aortic regurgitation while the "pressure" load associated with performing a Valsalva manoeuvre (VM) during resistance exercise may mimic the stress imposed on the heart by systemic hypertension or aortic stenosis. Despite widespread acceptance of the four-decade old Morganroth hypothesis in sports cardiology, some investigators have questioned whether such a divergent "athlete's heart" phenotype exists. Given this uncertainty, the purpose of this brief review is to re-evaluate the Morganroth hypothesis regarding: i) the acute effects of resistance exercise performed with a brief VM on LV wall stress, and the patterns of LV remodelling in resistance-trained athletes; ii) the acute effects of endurance exercise on biventricular wall stress, and the time course and pattern of LV and right ventricular (RV) remodelling with endurance training; and iii) the value of comparing "loading" conditions between athletes and patients with cardiac pathology. Copyright © 2018. Published by Elsevier B.V.

A multiscale modelling approach to understand atherosclerosis formation: A patient-specific case study in the aortic bifurcation

PubMed Central

Alimohammadi, Mona; Pichardo-Almarza, Cesar; Agu, Obiekezie; Díaz-Zuccarini, Vanessa

2017-01-01

Atherogenesis, the formation of plaques in the wall of blood vessels, starts as a result of lipid accumulation (low-density lipoprotein cholesterol) in the vessel wall. Such accumulation is related to the site of endothelial mechanotransduction, the endothelial response to mechanical stimuli and haemodynamics, which determines biochemical processes regulating the vessel wall permeability. This interaction between biomechanical and biochemical phenomena is complex, spanning different biological scales and is patient-specific, requiring tools able to capture such mathematical and biological complexity in a unified framework. Mathematical models offer an elegant and efficient way of doing this, by taking into account multifactorial and multiscale processes and mechanisms, in order to capture the fundamentals of plaque formation in individual patients. In this study, a mathematical model to understand plaque and calcification locations is presented: this model provides a strong interpretability and physical meaning through a multiscale, complex index or metric (the penetration site of low-density lipoprotein cholesterol, expressed as volumetric flux). Computed tomography scans of the aortic bifurcation and iliac arteries are analysed and compared with the results of the multifactorial model. The results indicate that the model shows potential to predict the majority of the plaque locations, also not predicting regions where plaques are absent. The promising results from this case study provide a proof of concept that can be applied to a larger patient population. PMID:28427316

Prophylactic Residual Aneurysmal Sac Embolization with Expandable Hydrogel Embolic Devices for Endoleak Prevention: Preliminary Study in Dogs

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

Hiraki, Takao; Pavcnik, Dusan, E-mail: pavcnikd@ohsu.edu; Uchida, Barry T.

2005-05-15

Objective. To explore the feasibility and efficacy of residual aneurysmal sac (RAS) embolization with the expandable hydrogel embolic device (EHED) in prevention of endoleaks in a surgically created and endoluminally treated abdominal aortic aneurysm (AAA). Methods. In eight dogs, an AAA was created by means of side-to-side anastomosis between the infrarenal abdominal aorta and inferior vena cava (IVC) with ligation of the IVC above and below the anastomotic end, followed by deployment of an endograft with holes. The RAS was then embolized with the EHED. One animal was killed immediately after RAS embolization and one animal died 12 hr aftermore » the procedure. Follow-up aortograms were obtained in six animals after 1 day (1 animal), 2 weeks and 6 months (1 animal), and 8 weeks (4 animals). Results. Four animals had no endoleaks on the follow-up aortograms. The remaining two animals with incomplete RAS embolization had moderate type III endoleaks. Type I or II endoleaks were not seen in any animals. Complications included RAS wall penetration by the devices with platinum wires in two animals (nos. 1 and 2), device migration into an aortic circulation through the endograft holes in two animals (nos. 2 and 3) or through distal interstices between the aortic wall and endograft in one animal (no. 8), aortic occlusion in three animals (nos. 3, 7, and 8), and RAS rupture in one animal (no. 7). Histologic examination showed expanded hydrogels occupying the RAS with associated mature or immature organized thrombus, fibrinous thrombus, or degenerate blood cells. Conclusion. RAS embolization was feasible with the EHED, although additional modifications to the device are required to avoid complications. Angiographic and histologic results suggested that RAS embolization with the EHED may help in the prevention of endoleaks.« less

Increased 18F-FDG Uptake Is Predictive of Rupture in a Novel Rat Abdominal Aortic Aneurysm Rupture Model

PubMed Central

English, Sean J.; Piert, Morand R.; Diaz, Jose A.; Gordon, David; Ghosh, Abhijit; D'Alecy, Louis G.; Whitesall, Steven E.; Sharma, Ashish K.; DeRoo, Elise P.; Watt, Tessa; Su, Gang; Henke, Peter K.; Eliason, Jonathan L.; Ailawadi, Gorav; Upchurch, Gilbert R.

2015-01-01

Objective To determine whether 18F-fluorodeoxyglucose (18F-FDG) micro–positron emission tomography (micro-PET) can predict abdominal aortic aneurysm (AAA) rupture. Background An infrarenal AAA model is needed to study inflammatory mechanisms that drive rupture. 18F-FDG PET can detect vascular inflammation in animal models and patients. Methods After exposing Sprague-Dawley rats to intra-aortic porcine pancreatic elastase (PPE) (12 U/mL), AAA rupture was induced by daily, subcutaneous, β-aminopropionitrile (BAPN, 300 mg/kg, N = 24) administration. Negative control AAA animals (N = 15) underwent daily saline subcutaneous injection after PPE exposure. BAPN-exposed animals that did not rupture served as positive controls [nonruptured AAA (NRAAA) 14d, N = 9]. Rupture was witnessed using radiotelemetry. Maximum standard uptakes for 18F-FDG micro-PET studies were determined. Aortic wall PAI-1, uPA, and tPA concentrations were determined by western blot analyses. Interleukin (IL)-1β, IL-6, IL-10, and MIP-2 were determined by Bio-Plex bead array. Neutrophil and macrophage populations per high-power field were quantified. Matrix metalloproteinase (MMP) activities were determined by zymography. Results When comparing ruptured AAA (RAAA) to NRAAA 14d animals, increased focal 18F-FDG uptakes were detected at subsequent sites of rupture (P = 0.03). PAI-1 expression was significantly less in RAAA tissue (P = 0.01), with comparable uPA and decreased tPA levels (P = 0.02). IL-1β (P = 0.04), IL-6 (P = 0.001), IL-10 (P = 0.04), and MIP-2 (P = 0.02)expression, neutrophil (P = 0.02) and macrophage presence (P = 0.002), and MMP9 (P < 0.0001) activity were increased in RAAA tissue. Conclusions With this AAA rupture model, increased prerupture 18F-FDG uptake on micro-PET imaging was associated with increased inflammation in the ruptured AAA wall. 18F-FDG PET imaging may be used to monitor inflammatory changes before AAA rupture. PMID:24651130

Vitamin D Receptor Activation Reduces Angiotensin-II-Induced Dissecting Abdominal Aortic Aneurysm in Apolipoprotein E-Knockout Mice.

PubMed

Martorell, Sara; Hueso, Luisa; Gonzalez-Navarro, Herminia; Collado, Aida; Sanz, Maria-Jesus; Piqueras, Laura

2016-08-01

Abdominal aortic aneurysm (AAA) is a vascular disorder characterized by chronic inflammation of the aortic wall. Low concentrations of vitamin D3 are associated with AAA development; however, the potential direct effect of vitamin D3 on AAA remains unknown. This study evaluates the effect of oral treatment with the vitamin D3 receptor (VDR) ligand, calcitriol, on dissecting AAA induced by angiotensin-II (Ang-II) infusion in apoE(-/-) mice. Oral treatment with calcitriol reduced Ang-II-induced dissecting AAA formation in apoE(-/-) mice, which was unrelated to systolic blood pressure or plasma cholesterol concentrations. Immunohistochemistry and reverse-transcription polymerase chain reaction analysis demonstrated a significant increase in macrophage infiltration, neovessel formation, matrix metalloproteinase-2 and matrix metalloproteinase-9, chemokine (CCL2 [(C-C motif) ligand 2], CCL5 [(C-C motif) ligand 5], and CXCL1 [(C-X-C motif) ligand 1]) and vascular endothelial growth factor expression in suprarenal aortic walls of apoE(-/-) mice infused with Ang-II, and all were significantly reduced by cotreatment with calcitriol. Phosphorylation of extracellular signal-regulated kinases 1/2, p38 mitogen-activated protein kinase, and nuclear factor-κB was also decreased in the suprarenal aortas of apoE(-/-) mice cotreated with calcitriol. These effects were accompanied by a marked increase in VDR-retinoid X receptor (RXR) interaction in the aortas of calcitriol-treated mice. In vitro, VDR activation by calcitriol in human endothelial cells inhibited Ang-II-induced leukocyte-endothelial cell interactions, morphogenesis, and production of endothelial proinflammatory and angiogenic chemokines through VDR-RXR interactions, and knockdown of VDR or RXR abolished the inhibitory effects of calcitriol. VDR activation reduces dissecting AAA formation induced by Ang-II in apoE(-/-) mice and may constitute a novel therapeutic strategy to prevent AAA progression. © 2016 American Heart Association, Inc.

Carotid intima-media thickness and elastic properties of aortas in normotensive children of hypertensive parents.

PubMed

Yildirim, Ali; Kosger, Pelin; Ozdemir, Gokmen; Sahin, Fezan Mutlu; Ucar, Birsen; Kilic, Zubeyir

2015-09-01

A significant correlation between hypertension history and high blood pressure has been observed with regard to age, race and gender. Investigating carotid intima-media thickness and aortic stiffness prior to the development of hypertension in children of hypertensive parents enabled us to evaluate these patients for subclinical atherosclerosis. We compared carotid intima-media thickness, aortic strain, distensibility, stiffness indices and elastic modulus in 67 normotensive children whose parents had a diagnosis of essential hypertension and 39 normotensive children with no parental history of hypertension. Although there were no significant differences between the two groups in terms of systolic blood pressure, diastolic blood pressure, average blood pressure and pulse pressure (P>0.05), systolic blood pressures were higher among patients 15 years and older in the study group. No significant differences were noted between the control and study groups regarding interventricular septal thickness, left-ventricular posterior wall thickness, left-ventricular systolic and diastolic diameter and aortic annulus diameter (P>0.05). The left atrium diameter was larger in the study group compared with that in the control group, mainly because of the values of the 15-year-old and older children (P=0.01). The mean, maximum and minimum values of carotid intima-media thickness were significantly different in the study group compared with the control group among all age groups (P<0.001, P<0.001, P=0.006, respectively). Aortic systolic and diastolic diameters were larger in normotensive children of hypertensive parents compared with the control group (P=0.014, P=0.001, respectively). Although there were no differences between the study and control groups regarding aortic strain, aortic distensibility, elastic modulus and stiffness indices (P>0.05), aortic distensibility was lower, and aortic stiffness indices were higher among children 15 years and older in the study group. An increase in the carotid intima-media thickness in all age groups and a decrease in aortic elastic properties in 15-year-old and older children of hypertensive parents may indicate subclinical atherosclerosis in these apparently healthy children.

Breast necrosis secondary to vasopressor extravasation: management using indocyanine green angiography and omental flap closure.

PubMed

Hagopian, Thomas M; Ghareeb, Paul A; Arslanian, Brian H; Moosavi, Benjamin L; Carlson, Grant W

2015-01-01

Extravasation is a rare but serious complication of vasopressor administration. A 60-year-old female who underwent ascending and hemiarch repair of the aorta along with aortic valve replacement developed extensive right breast and chest wall necrosis after vasopressor extravasation from an internal jugular vein central line. The patient underwent a total mastectomy due to deep tissue necrosis detected by laser-assisted indocyanine green dye angiography, and eventually required omental flap reconstruction to obtain adequate sternal coverage. This case represents a previously unreported complication of internal jugular central line extravasation of vasopressors with resultant breast and chest wall necrosis, and highlights the utility of the omentum in chest wall reconstruction. © 2015 Wiley Periodicals, Inc.

N-(2-Aminoethyl) Ethanolamine-Induced Morphological, Biochemical, and Biophysical Alterations in Vascular Matrix Associated With Dissecting Aortic Aneurysm

PubMed Central

Chen, Zhenping; Xu, Ya; Bujalowski, Paul; Oberhauser, Andres F.; Boor, Paul J.

2015-01-01

Dissecting aortic aneurysm (DAA) is an extended tear in the wall of the aorta along the plane of the vascular media. Our previous studies indicated in a developmental animal model, that DAA was related to pathological alteration in collagen, especially collagen type III. Accordingly, in the present studies, neonatal aortic vascular smooth muscle cells (VSMC) and timed pregnant Sprague-Dawley rat dams were treated with N-(2-aminoethyl) ethanolamine (AEEA), which, as shown previously, causes DAA in offspring. Morphological changes in extracellular matrix (ECM) produced by VSMC in vitro were detailed with scanning electron microscopy (SEM), and biochemical changes in cells and ECM produced by VSMCs were defined by Western blotting. Biophysical changes of the collagen extracted from both the ECM produced by VSMC and extracted from fetal rat aortas were studied with atomic force microscopy (AFM). ECM disruption and irregularities were observed in VSMCs treated with AEEA by SEM. Western blotting showed that collagen type I was much more extractable, accompanied by a decrease of the pellet size after urea buffer extraction in the AEEA-treated VSMC when compared with the control. AFM found that collagen samples extracted from the fetal rat aortas of the AEEA-treated dam, and in the in vitro formed ECM prepared by decellularization, became stiffer, or more brittle, indicating that the 3D organization associated with elasticity was altered by AEEA exposure. Our results show that AEEA causes significant morphological, biochemical, and biomechanical alterations in the ECM. These in vitro and in vivo strategies are advantageous in elucidating the underlying mechanisms of DAA. PMID:26443843

Application of thoracic endovascular aortic repair (TEVAR) in treating dwarfism with Stanford B aortic dissection: A case report.

PubMed

Qiu, Jian; Cai, Wenwu; Shu, Chang; Li, Ming; Xiong, Qinggen; Li, Quanming; Li, Xin

2018-04-01

To apply thoracic endovascular aortic repair (TEVAR) to treat dwarfism complicated with Stanford B aortic dissection. In this report, we presented a 63-year-old male patient of dwarfism complicated with Stanford B aortic dissection successfully treated with TEVAR. He was diagnosed with dwarfism complicated with Stanford B aortic dissection. After conservative treatment, the male patient underwent TEVAR at 1 week after hospitalization. After operation, he presented with numbness and weakness of his bilateral lower extremities, and these symptoms were significantly mitigated after effective treatment. At 1- and 3-week after TEVAR, the aorta status was maintained stable and restored. The patient obtained favorable clinical prognosis and was smoothly discharged. During subsequent follow-up, he remained physically stable. TEVAR is probably an option for treating dwarfism complicated with Stanford B aortic dissection, which remains to be validated by subsequent studies with larger sample size.

A clampless and sutureless aortic anastomosis technique using an endograft connector for aortoiliac occlusive disease in which the aorta cannot be clamped or sewn due to calcification or scarring.

PubMed

Papadimitriou, Dimitrios; Mayer, Dieter; Lachat, Mario; Pecoraro, Felice; Frauenfelder, Thomas; Pfammatter, Thomas; Ueda, Hideki; Donas, Konstantinos; Veith, Frank J; Rancic, Zoran

2012-10-01

Bypass surgery in aortoiliac or aortofemoral occlusive disease can be technically demanding and hazardous due to huge calcifications and/or patient co-morbidities. We report about mid-term results of a telescoping sutureless aortic anastomosis technique using endografts as connectors to address such challenging situations. This is a single-center experience (2004-2011) in seven patients (63 ± 6 years) requiring aortoiliac (three) or aortofemoral (four) bypass surgery. In six cases, an aortic stent graft was telescoped into the infrarenal aorta and partly deployed within the aorta and partly outside the aorta. In the first case, a bifurcated stent graft was deployed and the iliac legs were prolonged extra-anatomically with surgical grafts to reach the femoral bifurcation. In the following five cases, a tapered tubular stent graft was deployed through the aortic wall, landing inside a bifurcated surgical graft that was extra-anatomically connected to the iliac or femoral arteries. In the last case, which presented a hostile abdomen and high-risk for extensive surgery, a similar technique was used, but on the iliac artery level. In that case, an iliac stent graft re-loaded 'upside down' was deployed through the left common iliac wall, landing distally inside a hand-made 10 × 10 mm bifurcated surgical graft that was extra-anatomically connected to the left external iliac artery and to the right femoral artery. The distal anastomoses on the seven cases were performed either with running sutures (ten) or with VORTEC (four). Telescoping aortic and/or iliac anastomosis was successful in all patients. There was no perioperative mortality. One patient developed postoperative hyperperfusion of the left leg and necessitated fasciotomy. During a mean follow-up of 1.8 ± 2 years (minimum: 270 days, maximum: 7.1 years), all of the grafts remained patent and there was neither stent-graft migration nor stenosis on the level of the aortic or iliofemoral connection. One patient showed disease progression and required percutaneous transluminal angioplasty on the external iliac artery during follow-up. The uneventful perioperative course in these seven patients, with a follow-up of up to six years, underscores that this new technique can be considered in patients with aortoiliac or aortofemoral occlusive disease and in whom clamping and/or anastomosis is expected to be cumbersome or impossible.

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

Ameli-Renani, S., E-mail: seyedameli@doctors.org.uk; Das, R., E-mail: raj.das@stgeorges.nhs.uk; Weller, A., E-mail: alweller@gmail.com

We report the first case of intervention for a proximal type 1 endoleak following Nellix endovascular aneurysm sealing repair of an aortic aneurysm. This was complicated by migration of Onyx into one of the Nellix graft limbs causing significant stenosis. Subsequent placement of a covered stent to affix the Onyx between the stent and the wall of the Nellix endograft successfully restored stent patency.

Nonlinear analysis of aortic flow in living dogs.

NASA Technical Reports Server (NTRS)

Ling, S. C.; Atabek, H. B.; Letzing, W. G.; Patel, D. J.

1973-01-01

A nonlinear theory which considered the convective accelerations of blood and the nonlinear elastic behavior and taper angle of the vascular wall was used to study the nature of blood flow in the descending thoracic aorta of living dogs under a wide range of pressures and flows. Velocity profiles, wall friction, and discharge waves were predicted from locally measured input data about the pressure-gradient wave and arterial distention. The results indicated that a major part of the mean pressure gradient was balanced by convective accelerations; the theory, which took this factor into account, predicted the correct velocity distributions and flow waves.

Evaluation of the effects of glimepiride (Amaryl) and repaglinide (novoNorm) on atherosclerosis progression in high cholesterol-fed male rabbits

PubMed Central

Hadi, Najah R.; Al-Amran, Fadhil; Hussein, Mohammad A. A.; Rezeg, Fadhil A.

2012-01-01

Background: Atherosclerosis is an inflammatory disease of the blood vessel wall, characterized in early stages by endothelial dysfunction, recruitment and activation of monocyte/macrophages. Glimepiride is one of the third generation sulphonylurea drugs, useful for control of diabetes mellitus type two and it may exert anti inflammatory activity, by induction of nitric oxide production or through selective suppression of the cyclooxygenase pathway. Repaglinide is a new hypoglycemic agent, and a member of the carbamoylmethyl benzoic acid family. Some results from the literature demonstrate that repaglinide has favorable effects on the parameters of antioxidative balance. Objectives: The objective of the present study was to assess the effect of glimepiride and repaglinide on atherosclerosis via interfering with the inflammatory and oxidative pathways. Materials and Methods: Twenty four local domestic male rabbits were involved in this study. The animals were randomly divided into four groups; Group I rabbits fed normal chow (oxiod) diet for 10 weeks. Group II rabbits were fed with 1% cholesterol enriched diet. Group III rabbits were fed with 1% cholesterol enriched diet together with Glimepiride (0.1 mg/kg once daily before morning feed). Group IV rabbits were fed with 1% cholesterol enriched diet together with Repaglinide (0.3 mg/kg once daily before morning feed). Blood samples were collected before (0 time) and every two weeks of experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), High-density lipoprotein cholesterol (HDL-C), high sensitive C - reactive protein (hsCRP), Interleukin – 6 (IL-6) and Tumor Necrosis Factor alpha (TNF-α) levels. At the end of 10 weeks, the aorta was removed for measurement of aortic Malondialdehyde (MDA), reduced glutathione (GSH) and aortic intimal thickness. Results: Glimepiride and repaglinide treatment did show significant effect on lipid parameters compared with induced untreated group (P < 0.05). Also, they significantly reduced the elevation in hsCRP, IL-6, TNF-α, aortic MDA and aortic intimal thickness compared with induced untreated group (P < 0.05), and they helped to restore the aortic GSH levels (P < 0.05). Conclusions: Glimepiride and repaglinide may reduce atherosclerosis progression in hypercholesterolemic rabbits by interfering with the inflammatory and oxidative pathways without affecting lipid parameters. PMID:22346138

Bio-chemo-mechanics of thoracic aortic aneurysms.

PubMed

Wagenseil, Jessica E

2018-03-01

Most thoracic aortic aneurysms (TAAs) occur in the ascending aorta. This review focuses on the unique bio-chemo-mechanical environment that makes the ascending aorta susceptible to TAA. The environment includes solid mechanics, fluid mechanics, cell phenotype, and extracellular matrix composition. Advances in solid mechanics include quantification of biaxial deformation and complex failure behavior of the TAA wall. Advances in fluid mechanics include imaging and modeling of hemodynamics that may lead to TAA formation. For cell phenotype, studies demonstrate changes in cell contractility that may serve to sense mechanical changes and transduce chemical signals. Studies on matrix defects highlight the multi-factorial nature of the disease. We conclude that future work should integrate the effects of bio-chemo-mechanical factors for improved TAA treatment.

Turbulence downstream of subcoronary stentless and stented aortic valves.

PubMed

Funder, Jonas Amstrup; Frost, Markus Winther; Wierup, Per; Klaaborg, Kaj-Erik; Hjortdal, Vibeke; Nygaard, Hans; Hasenkam, J Michael

2011-08-11

Regions of turbulence downstream of bioprosthetic heart valves may cause damage to blood components, vessel wall as well as to aortic valve leaflets. Stentless aortic heart valves are known to posses several hemodynamic benefits such as larger effective orifice areas, lower aortic transvalvular pressure difference and faster left ventricular mass regression compared with their stented counterpart. Whether this is reflected by diminished turbulence formation, remains to be shown. We implanted either stented pericardial valve prostheses (Mitroflow), stentless valve prostheses (Solo or Toronto SPV) in pigs or they preserved their native valves. Following surgery, blood velocity was measured in the cross sectional area downstream of the valves using 10MHz ultrasonic probes connected to a dedicated pulsed Doppler equipment. As a measure of turbulence, Reynolds normal stress (RNS) was calculated at two different blood pressures (baseline and 50% increase). We found no difference in maximum RNS measurements between any of the investigated valve groups. The native valve had significantly lower mean RNS values than the Mitroflow (p=0.004), Toronto SPV (p=0.008) and Solo valve (p=0.02). There were no statistically significant differences between the artificial valve groups (p=0.3). The mean RNS was significantly larger when increasing blood pressure (p=0.0006). We, thus, found no advantages for the stentless aortic valves compared with stented prosthesis in terms of lower maximum or mean RNS values. Native valves have a significantly lower mean RNS value than all investigated bioprostheses. Copyright © 2011 Elsevier Ltd. All rights reserved.

Traumatic rupture of the aortic isthmus: program of selective management.

PubMed

Pate, J W; Gavant, M L; Weiman, D S; Fabian, T C

1999-01-01

Two hypotheses were investigated: (1) helical computed tomography (CT) of the chest on victims of decelerating trauma can yield a diagnosis of, or "rule out," a traumatic rupture of the aorta (TRA) without the need for an aortogram; and (2) selective delay of aortic repair can be safely accomplished through a medical management protocol. Screening helical CT examinations were done on 6169 victims of blunt thoracic trauma; 47 were found to have TRA; in 8, indirect but nondiagnostic findings not clarified by an aortogram led to surgical exploration. The sensitivity of helical CT was higher than that of aortograms, and a "normal" helical CT scan was never associated with a proved TRA. It is estimated that the use of helical CT has resulted in at least a 40% to 50% decrease in the need for aortograms, in addition to yielding rapid, noninvasive valuable information about other injuries. Drugs (beta-blockers +/- vasodilators) to decrease the stress in the aortic wall were used in 93 patients when the diagnosis was suspected and were continued as necessary through the evaluation, stabilization, and until the aorta was cross-clamped at operation. Elective, delayed operation was done between 2 days and 25 months in 15 patients who were deemed to be excessive risks for emergency aortic repair; there were 2 deaths (13. 3%). Eleven patients never had aortic repair. No patient maintained on this protocol, whether repaired emergently, electively, or not at all, developed free rupture of the periaortic hematoma and death from TRA.

Spectrum of Abdominal Aortic Disease in a Tertiary Health Care Setup: MDCT Based Observational Study

PubMed Central

Kumar, DG Santosh; Gadabanahalli, Karthik; Kalyanpur, Arjun

2016-01-01

Introduction Abdominal aortic disease is an important cause of clinical disability that requires early detection by imaging methods for prompt and effective management. Understanding regional disease pattern and prevalence has a bearing on healthcare management and resource planning. Non-invasive, conclusive imaging strategy plays an important role in the detection of disease. Multi-Detector Computed Tomography (MDCT) with its technological developments provides affordable, accurate and comprehensive imaging solution. Aim To evaluate regional demography of abdominal aortic disease spectrum detected using MDCT imaging data in a tertiary hospital. Materials and Methods A descriptive study was conducted based on MDCT imaging data of patients who were investigated with clinical diagnosis of abdominal aortic disease, from March 2008-2010, over a period of 24 months. Patients were examined with the contrast-enhanced MDCT examination. Morphological diagnosis of the aortic disease was based on changes in relative aortic caliber, luminal irregularity, presence of wall calcification, dissection or thrombus and evidence of major branch occlusion. Patients were categorized into four groups based on imaging findings. MDCT information and associated clinical parameters were examined and correlated to management of patient. Descriptive statistical data, namely mean, standard deviation and frequency of disease were evaluated. Results A total of 90 out of 210 patients (43%) were detected with the abdominal aortic abnormality defined by imaging criteria. Group I, comprising of patients with atherosclerosis –including those with complications, constituted 65.5% of the patients. Group II represented patients with aneurysms (45.5%). Group III, consisting of 32.2% of the patients, contained those with dissections. The rest of the patients, including patients with aorto-arteritis, were classified as group IV. Eight patients with aneurysm and one patient with aorto-arteritis were considered for surgical treatment. Ten patients with dissection underwent endovascular procedure. Rest of the patients was managed conservatively. Conclusion Aortic disease was observed in 43% of investigated patients. Atherosclerosis with and without aortic aneurysm constituted the largest group. MDCT provided comprehensive information about the lesion and associated complications. In view of the wider availability and desired imaging qualities, MDCT provided optimal information for diagnosis and management of aortic pathology. Majority of our patients (90%) were treated conservatively. PMID:28050476

Variations in local elastic modulus along the length of the aorta as observed by use of a scanning haptic microscope (SHM).

PubMed

Moriwaki, Takeshi; Oie, Tomonori; Takamizawa, Keiichi; Murayama, Yoshinobu; Fukuda, Toru; Omata, Sadao; Kanda, Keiichi; Nakayama, Yasuhide

2011-12-01

Variations in microscopic elastic structures along the entire length of canine aorta were evaluated by use of a scanning haptic microscope (SHM). The total aorta from the aortic arch to the abdominal aorta was divided into 6 approximately equal segments. After embedding the aorta in agar, it was cut into horizontal circumferential segments to obtain disk-like agar portions containing ring-like samples of aorta with flat surfaces (thickness, approximately 1 mm). The elastic modulus and topography of the samples under no-load conditions were simultaneously measured along the entire thickness of the wall by SHM by using a probe with a diameter of 5 μm and a spatial resolution of 2 μm at a rate of 0.3 s/point. The elastic modulus of the wall was the highest on the side of the luminal surface and decreased gradually toward the adventitial side. This tendency was similar to that of the change in the elastin fiber content. During the evaluation of the mid-portion of each tunica media segment, the highest elastic modulus (40.8 ± 3.5 kPa) was identified at the thoracic section of the aorta that had the highest density of elastic fibers. Under no-load conditions, portions of the aorta with high elastin density have a high elastic modulus.

Effects of Leaflet Design on Transvalvular Gradients of Bioprosthetic Heart Valves.

PubMed

Dabiri, Yaghoub; Ronsky, Janet; Ali, Imtiaz; Basha, Ameen; Bhanji, Alisha; Narine, Kishan

2016-12-01

Bioprosthetic aortic valves (BAVs) are becoming the prostheses of choice in heart valve replacement. The objective of this paper is to assess the effects of leaflet geometry on the mechanics and hemodynamics of BAVs in a fluid structure interaction model. The curvature and angle of leaflets were varied in 10 case studies whereby the following design parameters were altered: a circular arch, a line, and a parabola for the radial curvature, and a circular arch, a spline, and a parabola for the circumferential curvature. Six different leaflet angles (representative of the inclination of the leaflets toward the surrounding aortic wall) were analyzed. The 3-dimensional geometry of the models were created using SolidWorks, Pointwise was used for meshing, and Comsol Multiphysics was used for implicit finite element calculations. Realistic loading was enforced by considering the time-dependent strongly-coupled interaction between blood flow and leaflets. Higher mean pressure gradients as well as von Mises stresses were obtained with a parabolic or circular curvature for radial curvature or a parabolic or spline curvature for the circumferential curvature. A smaller leaflet angle was associated with a lower pressure gradient, and, a lower von Mises stress. The leaflet curvature and angle noticeably affected the speed of valve opening, and closing. When a parabola was used for circumferential or radial curvature, leaflets displacements were asymmetric, and they opened and closed more slowly. A circular circumferential leaflet curvature, a linear leaflet radial curvature, and leaflet inclination toward the surrounding aortic wall were associated with superior BAVs mechanics.

Elective implantation of covered stents for coarctation and recoarctation in adolescents and adults.

PubMed

Alcibar, Juan; Blanco, Roberto; Fernandez, Luis; Arriola, Josune; Garcia, Koldobika; Peña, Natividad; Inguanzo, Ramón; Voces, Roberto; Castellanos, Enrique; Montes, Pedro M

2013-06-01

Stent implantation is an effective therapy for aortic coarctation and recoarctation. However, in adolescents and adults, aortic wall rupture and dissection can occur, as well as aneurysms during follow-up. In order to reduce these complications, we electively implant covered stents. Since 2005, we have performed the procedure using femoral access in 17 patients (2 adolescents and 15 adults), 16 electively and 1 as a rescue procedure. We used the Mullins technique in all cases, implanting a NuMED(®) covered stent. Good stent apposition was achieved in all 17 procedures; 8 patients required a distal flare. Gradient was reduced from 40 (16) mmHg to 2 (2) mmHg (P<.001) and lumen diameter increased from 4 (2) mm to 19 (3) mm (P<.001). Two exceptional cases are discussed: one patient with aortic wall rupture who underwent a rescue procedure using a stent within a covered stent and another patient with total obstruction and intercostal aneurysm in whom the outcome was fatal at 48 h postprocedure (autopsy is shown). Four-year clinical follow-up included Doppler echocardiography; an additional imaging technique was required in 13 patients. All patients recovered well and there were no complications. Covered stents are effective in treating coarctation and recoarctation in adolescents and adults, are the treatment of choice in patients with complex anatomy, and must be available in the operating room as a rescue device when implanting a conventional stent. Copyright © 2012 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Total ellipse of the heart valve: the impact of eccentric stent distortion on the regional dynamic deformation of pericardial tissue leaflets of a transcatheter aortic valve replacement

PubMed Central

Gunning, Paul S.; Saikrishnan, Neelakantan; Yoganathan, Ajit P.; McNamara, Laoise M.

2015-01-01

Transcatheter aortic valve replacements (TAVRs) are a percutaneous alternative to surgical aortic valve replacements and are used to treat patients with aortic valve stenosis. This minimally invasive procedure relies on expansion of the TAVR stent to radially displace calcified aortic valve leaflets against the aortic root wall. However, these calcium deposits can impede the expansion of the device causing distortion of the valve stent and pericardial tissue leaflets. The objective of this study was to elucidate the impact of eccentric TAVR stent distortion on the dynamic deformation of the tissue leaflets of the prosthesis in vitro. Dual-camera stereophotogrammetry was used to measure the regional variation in strain in a leaflet of a TAVR deployed in nominal circular and eccentric (eccentricity index = 28%) orifices, representative of deployed TAVRs in vivo. It was observed that (i) eccentric stent distortion caused incorrect coaptation of the leaflets at peak diastole resulting in a ‘peel-back’ leaflet geometry that was not present in the circular valve and (ii) adverse bending of the leaflet, arising in the eccentric valve at peak diastole, caused significantly higher commissure strains compared with the circular valve in both normotensive and hypertensive pressure conditions (normotension: eccentric = 13.76 ± 2.04% versus circular = 11.77 ± 1.61%, p = 0.0014, hypertension: eccentric = 15.07 ± 1.13% versus circular = 13.56 ± 0.87%, p = 0.0042). This study reveals that eccentric distortion of a TAVR stent can have a considerable impact on dynamic leaflet deformation, inducing deleterious bending of the leaflet and increasing commissures strains, which might expedite leaflet structural failure compared to leaflets in a circular deployed valve. PMID:26674192

Creation of Abdominal Aortic Aneurysms in Sheep by Extrapolation of Rodent Models: Is It Feasible?

PubMed

Verbrugghe, Peter; Verhoeven, Jelle; Clijsters, Marnick; Vervoort, Dominique; Coudyzer, Walter; Verbeken, Eric; Meuris, Bart; Herijgers, Paul

2018-06-07

Abdominal aortic aneurysms (AAAs) are a potentially deathly disease, needing surgical or endovascular treatment. To evaluate potentially new diagnostic tools and treatments, a large animal model, which resembles not only the morphological characteristics but also the pathophysiological background, would be useful. Rodent animal aneurysm models were extrapolated to sheep. Four groups were created: intraluminal infusion with an elastase-collagenase solution (n = 4), infusion with elastase-collagenase solution combined with proximal stenosis (n = 7), aortic xenograft (n = 3), and elastase-collagenase-treated xenograft (n = 4). At fixed time intervals (6, 12, and 24 weeks), computer tomography and autopsy with histological evaluation were performed. The described models had a high perioperative mortality (45%), due to acute aortic thrombosis or fatale hemorrhage. A maximum aortic diameter increase of 30% was obtained in the protease-stenosis group. In the protease-treated groups, some histological features of human AAAs, such as inflammation, thinning of the media, and loss of elastin could be reproduced. In the xenotransplant groups, a pronounced inflammatory reaction was visible at the start. In all models, inflammation decreased and fibrosis occurred at long follow-up, 24 weeks postoperatively. None of the extrapolated small animal aneurysm models could produce an AAA in sheep with similar morphological features as the human disease. Some histological findings of human surgical specimens could be reproduced in the elastase-collagenase-treated groups. Long-term histological evaluation indicated stabilization and healing of the aortic wall months after the initial stimulus. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Effect of statin therapy on serum activity of proteinases and cytokines in patients with abdominal aortic aneurysm

PubMed Central

Muehling, Bernd; Oberhuber, Alexander; Schelzig, Hubert; Bischoff, Gisela; Marx, Nikolaus; Sunder-Plassmann, Ludger; Orend, Karl H

2008-01-01

Background and aims: Metalloproteinases (MMPs) are considered to be key enzymes in the pathogenesis of abdominal aortic aneurysms (AAA), with elevated levels in diseased aorta and in patient sera. Statins seem to exert an inhibitory effect on MMP activity in the aortic wall. No data exist on the effect of statins on serum activity of MMPs and inflammatory cytokines (interleukins, IL). Methods: The serum activities of MMP2 and MMP9, osteoprotegerin (OPG), and IL6 and IL10 in 63 patients undergoing elective infrarenal aneurysm repair were measured on the day before surgery. Levels were correlated to statin therapy and aneurysm diameter. Results: There was no significant difference between the two groups in the activity of circulating levels of MMP2/9, OPG, and IL6/10 in patients with infrarenal aortic aneurysm. IL6 levels in patients with AAA larger than 6 cm were significantly elevated; differences in serum activities of MMP2/9, OPG, and IL10 were not related to AAA diameter. Conclusion: Serum activities of MMP2/9, OPG, and IL6/10 are not correlated to statin therapy; IL6 levels are higher in patients with large aneurysms. Hence the effect of statin therapy in the treatment of aneurismal disease remains to be elucidated. PMID:19337556

Quantifying Turbulent Kinetic Energy in an Aortic Coarctation with Large Eddy Simulation and Magnetic Resonance Imaging

NASA Astrophysics Data System (ADS)

Lantz, Jonas; Ebbers, Tino; Karlsson, Matts

2012-11-01

In this study, turbulent kinetic energy (TKE) in an aortic coarctation was studied using both a numerical technique (large eddy simulation, LES) and in vivo measurements using magnetic resonance imaging (MRI). High levels of TKE are undesirable, as kinetic energy is extracted from the mean flow to feed the turbulent fluctuations. The patient underwent surgery to widen the coarctation, and the flow before and after surgery was computed and compared to MRI measurements. The resolution of the MRI was about 7 × 7 voxels in axial cross-section while 50x50 mesh cells with increased resolution near the walls was used in the LES simulation. In general, the numerical simulations and MRI measurements showed that the aortic arch had no or very low levels of TKE, while elevated values were found downstream the coarctation. It was also found that TKE levels after surgery were lowered, indicating that the diameter of the constriction was increased enough to decrease turbulence effects. In conclusion, both the numerical simulation and MRI measurements gave very similar results, thereby validating the simulations and suggesting that MRI measured TKE can be used as an initial estimation in clinical practice, while LES results can be used for detailed quantification and further research of aortic flows.

Novel role of ADAMTS-5 protein in proteoglycan turnover and lipoprotein retention in atherosclerosis.

PubMed

Didangelos, Athanasios; Mayr, Ursula; Monaco, Claudia; Mayr, Manuel

2012-06-01

Atherosclerosis is initiated by the retention of lipoproteins on proteoglycans in the arterial intima. However, the mechanisms leading to proteoglycan accumulation and lipoprotein retention are poorly understood. In this study, we set out to investigate the role of ADAMTS-5 (a disintegrin and metalloprotease with thrombospondin motifs-5) in the vasculature. ADAMTS-5 was markedly reduced in atherosclerotic aortas of apolipoprotein E-null (apoE(-/-)) mice. The reduction of ADAMTS-5 was accompanied by accumulation of biglycan and versican, the major lipoprotein-binding proteoglycans, in atherosclerosis. ADAMTS-5 activity induced the release of ADAMTS-specific versican (DPEAAE(441)) and aggrecan ((374)ALGS) fragments as well as biglycan and link protein from the aortic wall. Fibroblast growth factor 2 (FGF-2) inhibited ADAMTS-5 expression in isolated aortic smooth muscle cells and blocked the spontaneous release of ADAMTS-generated versican and aggrecan fragments from aortic explants. In aortas of ADAMTS-5-deficient mice, DPEAAE(441) versican neoepitopes were not detectable. Instead, biglycan levels were increased, highlighting the role of ADAMTS-5 in the catabolism of vascular proteoglycans. Importantly, ADAMTS-5 proteolytic activity reduced the LDL binding ability of biglycan and released LDL from human aortic lesions. This study provides the first evidence implicating ADAMTS-5 in the regulation of proteoglycan turnover and lipoprotein retention in atherosclerosis.

Study of normal, fibrous and calcified aortic valve tissue by Raman and reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Rodrigues, Kátia Calligaris; Munin, Egberto; Alves, Leandro P.; Silveira, Fabrício L.; Junior, Landulfo S.; De Lima, Carlos J.; Lázzaro, João C.; De Souza, Genivaldo C.; Piotto, José A. B.; Pacheco, Marcos T. T.; Zângaro, Renato A.

2007-02-01

Several studies have identified the degree of aortic valve calcification as a strong predictor both for the progression and outcome of aortic stenosis. In industrialized countries, aortic valve stenosis is most frequently caused by progressive calcification and degeneration of aortic cusps. However, there are no accurate methods to quantify the extent of aortic valve calcification. To provide a non-invasive alternative to biopsy, a range of optical methods have been investigated, including Raman and reflectance spectroscopy. A Raman spectrum can be used to access the molecular constitution of a particular tissue and classify it. Raman spectroscopy is largely used in the quantification and evaluation of human atherosclerosis, being a powerful technique for performing biochemical analysis without tissue removal. Nevertheless, increased thickness and disorganization of the collagen fibre network and extracellular matrix are known to affect the diffuse spectral reflectance of the tissue. A catheter with the "6 around 1" configuration, the central fiber transmit laser radiation to the sample and the scattered light is collected by the other six surrounding fibers, was used both for Raman and reflectance spectroscopy. A white light (krypton lamp, flashtube Model FX 1160 Perkin Elmer, USA) excitation was used for reflectance measurements. A Ti-sapphire (785nm, Spectra Physics, model 3900S, USA) laser, pumped by an argon laser (Spectra Physics, model Stabilite 2017, USA) was used as the near infrared Raman set up. Several ex-vivo spectra of aortic valve samples were analyzed. The results show a promising way to differentiate normal, fibrous and calcified tissue in aortic valve.

Investigation of hemodynamics in the development of dissecting aneurysm within patient-specific dissecting aneurismal aortas using computational fluid dynamics (CFD) simulations.

PubMed

Tse, Kwong Ming; Chiu, Peixuan; Lee, Heow Pueh; Ho, Pei

2011-03-15

Aortic dissecting aneurysm is one of the most catastrophic cardiovascular emergencies that carries high mortality. It was pointed out from clinical observations that the aneurysm development is likely to be related to the hemodynamics condition of the dissected aorta. In order to gain more insight on the formation and progression of dissecting aneurysm, hemodynamic parameters including flow pattern, velocity distribution, aortic wall pressure and shear stress, which are difficult to measure in vivo, are evaluated using numerical simulations. Pulsatile blood flow in patient-specific dissecting aneurismal aortas before and after the formation of lumenal aneurysm (pre-aneurysm and post-aneurysm) is investigated by computational fluid dynamics (CFD) simulations. Realistic time-dependent boundary conditions are prescribed at various arteries of the complete aorta models. This study suggests the helical development of false lumen around true lumen may be related to the helical nature of hemodynamic flow in aorta. Narrowing of the aorta is responsible for the massive recirculation in the poststenosis region in the lumenal aneurysm development. High pressure difference of 0.21 kPa between true and false lumens in the pre-aneurismal aorta infers the possible lumenal aneurysm site in the descending aorta. It is also found that relatively high time-averaged wall shear stress (in the range of 4-8 kPa) may be associated with tear initiation and propagation. CFD modeling assists in medical planning by providing blood flow patterns, wall pressure and wall shear stress. This helps to understand various phenomena in the development of dissecting aneurysm. Copyright © 2011 Elsevier Ltd. All rights reserved.

Automated segmentation of the atrial region and fossa ovalis towards computer-aided planning of inter-atrial wall interventions.

PubMed

Morais, Pedro; Vilaça, João L; Queirós, Sandro; Marchi, Alberto; Bourier, Felix; Deisenhofer, Isabel; D'hooge, Jan; Tavares, João Manuel R S

2018-07-01

Image-fusion strategies have been applied to improve inter-atrial septal (IAS) wall minimally-invasive interventions. Hereto, several landmarks are initially identified on richly-detailed datasets throughout the planning stage and then combined with intra-operative images, enhancing the relevant structures and easing the procedure. Nevertheless, such planning is still performed manually, which is time-consuming and not necessarily reproducible, hampering its regular application. In this article, we present a novel automatic strategy to segment the atrial region (left/right atrium and aortic tract) and the fossa ovalis (FO). The method starts by initializing multiple 3D contours based on an atlas-based approach with global transforms only and refining them to the desired anatomy using a competitive segmentation strategy. The obtained contours are then applied to estimate the FO by evaluating both IAS wall thickness and the expected FO spatial location. The proposed method was evaluated in 41 computed tomography datasets, by comparing the atrial region segmentation and FO estimation results against manually delineated contours. The automatic segmentation method presented a performance similar to the state-of-the-art techniques and a high feasibility, failing only in the segmentation of one aortic tract and of one right atrium. The FO estimation method presented an acceptable result in all the patients with a performance comparable to the inter-observer variability. Moreover, it was faster and fully user-interaction free. Hence, the proposed method proved to be feasible to automatically segment the anatomical models for the planning of IAS wall interventions, making it exceptionally attractive for use in the clinical practice. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of robotic endovascular catheters for arch vessel cannulation.

PubMed

Riga, Celia V; Bicknell, Colin D; Hamady, Mohamad S; Cheshire, Nicholas J W

2011-09-01

Conventional catheter instability and embolization risk limits the adoption of endovascular therapy in patients with challenging arch anatomy. This study investigated whether arch vessel cannulation can be enhanced by a remotely steerable robotic catheter system. Seventeen clinicians with varying endovascular experience cannulated all arch vessels within two computed tomography-reconstructed pulsatile flow phantoms (bovine type I and type III aortic arches), under fluoroscopic guidance, using conventional and robotic techniques. Quantitative (catheterization times, catheter tip movements, vessel wall hits, catheter deflection) and qualitative metrics (Imperial College Complex Endovascular Cannulation Scoring Tool [IC3ST]) performance scores were compared. Robotic catheterization techniques resulted in a significant reduction in median carotid artery cannulation times and the median number of catheter tip movements for all vessels. Vessel wall contact with the aortic arch wall was reduced to a median of zero with robotic catheters. During stiff guidewire exchanges, robotic catheters maintained stability with zero deflection, independent of the distance the catheter was introduced into the carotid vessels. Overall IC3ST performance scores (interquartile range) were significantly improved using the robotic system: Type I arch score was 26/35 (20-30.8) vs 33/35 (31-34; P = .001), and type III arch score was 20.5/35 (16.5-28.5) vs 26.5/35 (23.5-28.8; P = .001). Low- and medium-volume interventionalists demonstrated an improvement in performance with robotic cannulation techniques. The high-volume intervention group did not show statistically significant improvement, but cannulation times, movements, and vessel wall hits were significantly reduced. Robotic technology has the potential to reduce the time, risk of embolization and catheter dislodgement, radiation exposure, and the manual skill required for carotid and arch vessel cannulation, while improving overall performance scores. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Computational Growth and Remodeling of Abdominal Aortic Aneurysms Constrained by the Spine.

PubMed

Farsad, Mehdi; Zeinali-Davarani, Shahrokh; Choi, Jongeun; Baek, Seungik

2015-09-01

Abdominal aortic aneurysms (AAAs) evolve over time, and the vertebral column, which acts as an external barrier, affects their biomechanical properties. Mechanical interaction between AAAs and the spine is believed to alter the geometry, wall stress distribution, and blood flow, although the degree of this interaction may depend on AAAs specific configurations. In this study, we use a growth and remodeling (G&R) model, which is able to trace alterations of the geometry, thus allowing us to computationally investigate the effect of the spine for progression of the AAA. Medical image-based geometry of an aorta is constructed along with the spine surface, which is incorporated into the computational model as a cloud of points. The G&R simulation is initiated by local elastin degradation with different spatial distributions. The AAA-spine interaction is accounted for using a penalty method when the AAA surface meets the spine surface. The simulation results show that, while the radial growth of the AAA wall is prevented on the posterior side due to the spine acting as a constraint, the AAA expands faster on the anterior side, leading to higher curvature and asymmetry in the AAA configuration compared to the simulation excluding the spine. Accordingly, the AAA wall stress increases on the lateral, posterolateral, and the shoulder regions of the anterior side due to the AAA-spine contact. In addition, more collagen is deposited on the regions with a maximum diameter. We show that an image-based computational G&R model not only enhances the prediction of the geometry, wall stress, and strength distributions of AAAs but also provides a framework to account for the interactions between an enlarging AAA and the spine for a better rupture potential assessment and management of AAA patients.

Computational Growth and Remodeling of Abdominal Aortic Aneurysms Constrained by the Spine

PubMed Central

Farsad, Mehdi; Zeinali-Davarani, Shahrokh; Choi, Jongeun; Baek, Seungik

2015-01-01

Abdominal aortic aneurysms (AAAs) evolve over time, and the vertebral column, which acts as an external barrier, affects their biomechanical properties. Mechanical interaction between AAAs and the spine is believed to alter the geometry, wall stress distribution, and blood flow, although the degree of this interaction may depend on AAAs specific configurations. In this study, we use a growth and remodeling (G&R) model, which is able to trace alterations of the geometry, thus allowing us to computationally investigate the effect of the spine for progression of the AAA. Medical image-based geometry of an aorta is constructed along with the spine surface, which is incorporated into the computational model as a cloud of points. The G&R simulation is initiated by local elastin degradation with different spatial distributions. The AAA–spine interaction is accounted for using a penalty method when the AAA surface meets the spine surface. The simulation results show that, while the radial growth of the AAA wall is prevented on the posterior side due to the spine acting as a constraint, the AAA expands faster on the anterior side, leading to higher curvature and asymmetry in the AAA configuration compared to the simulation excluding the spine. Accordingly, the AAA wall stress increases on the lateral, posterolateral, and the shoulder regions of the anterior side due to the AAA–spine contact. In addition, more collagen is deposited on the regions with a maximum diameter. We show that an image-based computational G&R model not only enhances the prediction of the geometry, wall stress, and strength distributions of AAAs but also provides a framework to account for the interactions between an enlarging AAA and the spine for a better rupture potential assessment and management of AAA patients. PMID:26158885

Developments in parallel grafts for aortic arch lesions.

PubMed

Kolvenbach, Ralf R; Rabin, Asaf; Karmeli, Ron; Alpaslan, Alper; Schwierz, Elizabeth

2016-06-01

Due to the shortage of commercially available off the shelf aortic arch grafts since the last years parallel grafts or chimney grafts have played an increasing role in the treatment of patients with aortic arch lesions. Although there are still issues with type endoleaks and gutters between the chimney graft and the aortic stent-graft remaining. We report our results with the Medtronic thoracic graft in combination with long self-expanding parallel grafts, to ensure an overlapping zone of more than 7 cm between the different grafts. Alternatively, sandwich configurations are used where a direct contact between the parallel graft and the aortic wall is avoided. We have placed a total of 65 parallel grafts into supra-aortic branches. In 21 cases chimney grafts were placed into the carotid artery, in most cases into the left common carotid artery. In 36 cases chimney grafts were placed into left subclavian artery. A maximum number of 4 parallel grafts were placed for total endovascular debranching. In addition, in 8 patients a parallel graft had to be placed into the innominate artery. There was a patency of 69% for all subclavian artery chimney grafts versus 73% for carotid artery parallel grafts. Of note is a stroke rate of 5.2% in all these cases. Only 2 of the patients with an occluded left subclavian artery chimney graft required a bypass procedure for arm claudication or ischemia. We had a primary type I endoleak rate of 28%. In almost 25% secondary interventions were required mainly to treat type I leaks, in those cases where the leak did not resolve spontaneously. The overall mortality rate was 3.5%. The results of parallel graft in the aortic arch are promising, but of major concern is still the high rate of type I endoleaks as well as the neurological complication rate, most probably due to catheter manipulation in patients with severe atherosclerotic arch lesions.

Abdominal Aortic Hemodynamics in Intermittent Claudication Patients at Rest and During Dynamic Pedaling Exercise

PubMed Central

Cheng, Christopher P.; Taylor, Charles A.; Dalman, Ronald L.

2015-01-01

Introduction Lower extremity exercise has been shown to eliminate adverse hemodynamics conditions, such as low and oscillating blood flow and wall shear stress, in the abdominal aortas of healthy young and older adults. Methods We use cine phase-contrast magnetic resonance imaging and a custom MRI-compatible exercise cycle to quantify hemodynamic changes due to pedaling exercise in patients diagnosed with intermittent claudication. Results and Conclusions With only an average heart increase of 35±18% and exercise workload of 36±16 Watts, the patients experienced approximately 3- and 6-fold increases in blood flow, and 4- and 16-fold increases in wall shear stress at the supraceliac and infrarenal aortic locations, respectively. Also, all oscillations in flow and shear stress at rest were eliminated with exercise. Claudication patients experience 3 to 4-fold lower oscillations in flow and shear stress at rest as compared to healthy age-matched controls, likely due to reduced distal arterial compliance as a result of distal atherosclerosis. The magnitude of flow and shear oscillatory indices may be good indicators of distal arterial compliance and health, and may provide predictive power for the efficacy of focal interventions. PMID:26315797

The effect of flow recirculation on abdominal aortic aneurysm

NASA Astrophysics Data System (ADS)

Taib, Ishkrizat; Amirnordin, Shahrin Hisham; Madon, Rais Hanizam; Mustafa, Norrizal; Osman, Kahar

2012-06-01

The presences of flow recirculation at the abdominal aortic aneurysm (AAA) region yield the unpredictable failure of aneurismal wall. The failure of the aneurismal wall is closely related to the hemodynamic factor. Hemodynamic factor such as pressure and velocity distribution play a significance role of aneurysm growth and rupture. By using the computational approach, the influence of hemodynamic factor is investigated using computational fluid dynamic (CFD) method on the virtual AAA model. The virtual 3D AAAs model was reconstructed from Spiral Computed Tomography scan (CT-scan). The blood flow is assumed as being transient, laminar and Newtonian within a rigid section of the vessel. The blood flow also driven by an imposed of pressure gradient in the form of physiological waveform. The pulsating blood flow is also considered in this simulation. The results on pressure distribution and velocity profile are analyzed to interpret the behaviour of flow recirculation. The results show the forming of vortices is seen at the aneurysm bulge. This vortices is form at the aneurysm region then destroyed rapidly by flow recirculation. Flow recirculation is point out much higher at distal end of aneurysm closed to iliac bifurcation. This phenomenon is managed to increase the possibility of aneurysm growth and rupture.

Aortic stiffness and calcification in men in a population-based international study.

PubMed

Sekikawa, Akira; Shin, Chol; Curb, J David; Barinas-Mitchell, Emma; Masaki, Kamal; El-Saed, Aiman; Seto, Todd B; Mackey, Rachel H; Choo, Jina; Fujiyoshi, Akira; Miura, Katsuyuki; Edmundowicz, Daniel; Kuller, Lewis H; Ueshima, Hirotsugu; Sutton-Tyrrell, Kim

2012-06-01

Aortic stiffness, a hallmark of vascular aging, is an independent risk factor of cardiovascular disease and all-cause mortality. The association of aortic stiffness with aortic calcification in middle-aged general population remains unknown although studies in patients with end-stage renal disease or elderly subjects suggest that aortic calcification is an important determinant of aortic stiffness. The goal of this study was to examine the association of aortic calcification and stiffness in multi-ethnic population-based samples of relatively young men. We examined the association in 906 men aged 40-49 (81 Black Americans, 276 Japanese Americans, 258 White Americans and 291 Koreans). Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV) using an automated waveform analyzer. Aortic calcification from aortic arch to iliac bifurcation was evaluated using electron-beam computed tomography. Aortic calcium score was calculated and was categorized into four groups: zero (n=303), 1-100 (n=411), 101-300 (n=110), and 401+ (n=82). Aortic calcification category had a significant positive association with cfPWV after adjusting for age, race, and mean arterial pressure (mean (standard error) of cfPWV (cm/s) from the lowest to highest categories: 836 (10), 850 (9), 877 (17) and 941 (19), P for trend <0.001). The significant positive association remained after further adjusting for other cardiovascular risk factors. The significant positive association was also observed in each race group. The results suggest that aortic calcification can be one mechanism for aortic stiffness and that the association of aortic calcification with stiffness starts as early as the 40s. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Aortic stiffness and calcification in men in a population-based international study

PubMed Central

Sekikawa, Akira; Shin, Chol; Curb, J. David; Barinas-Mitchell, Emma; Masaki, Kamal; El-Saed, Aiman; Seto, Todd B.; Mackey, Rachel H.; Choo, Jina; Fujiyoshi, Akira; Miura, Katsuyuki; Edmundowicz, Daniel; Kuller, Lewis H.; Ueshima, Hirotsugu; Sutton-Tyrrell, Kim

2012-01-01

Objectives Aortic stiffness, a hallmark of vascular aging, is an independent risk factor of cardiovascular disease and all-cause mortality. The association of aortic stiffness with aortic calcification in middle-aged general population remains unknown although studies in patients with end-stage renal disease or elderly subjects suggest that aortic calcification is an important determinant of aortic stiffness. The goal of this study was to examine the association of aortic calcification and stiffness in multi-ethnic population-based samples of relatively young men. Methods We examined the association in 906 men aged 40–49 (81 Black Americans, 276 Japanese Americans, 258 White Americans and 291 Koreans). Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV) using an automated waveform analyzer. Aortic calcification from aortic arch to iliac bifurcation was evaluated using electron-beam computed tomography. Results Aortic calcium score was calculated and was categorized into four groups: zero (n=303), 1–100 (n=411), 101–300 (n=110), and 401+ (n=82). Aortic calcification category had a significant positive association with cfPWV after adjusting for age, race, and mean arterial pressure (mean (standard error) of cfPWV (cm/second) from the lowest to highest categories: 836 (10), 850 (9), 877 (17) and 941 (19), p for trend <0.001). The significant positive association remained after further adjusting for other cardiovascular risk factors. The significant positive association was also observed in each race group. Conclusions The results suggest that aortic calcification can be one mechanism for aortic stiffness and that the association of aortic calcification with stiffness starts as early as the 40’s. PMID:22537531

A reduced-dimensional model for near-wall transport in cardiovascular flows

PubMed Central

Hansen, Kirk B.

2015-01-01

Near-wall mass transport plays an important role in many cardiovascular processes, including the initiation of atherosclerosis, endothelial cell vasoregulation, and thrombogenesis. These problems are characterized by large Péclet and Schmidt numbers as well as a wide range of spatial and temporal scales, all of which impose computational difficulties. In this work, we develop an analytical relationship between the flow field and near-wall mass transport for high-Schmidt-number flows. This allows for the development of a wall-shear-stress-driven transport equation that lies on a codimension-one vessel-wall surface, significantly reducing computational cost in solving the transport problem. Separate versions of this equation are developed for the reaction-rate-limited and transport-limited cases, and numerical results in an idealized abdominal aortic aneurysm are compared to those obtained by solving the full transport equations over the entire domain. The reaction-rate-limited model matches the expected results well. The transport-limited model is accurate in the developed flow regions, but overpredicts wall flux at entry regions and reattachment points in the flow. PMID:26298313

Quantification of common carotid artery and descending aorta vessel wall thickness from MR vessel wall imaging using a fully automated processing pipeline.

PubMed

Gao, Shan; van 't Klooster, Ronald; Brandts, Anne; Roes, Stijntje D; Alizadeh Dehnavi, Reza; de Roos, Albert; Westenberg, Jos J M; van der Geest, Rob J

2017-01-01

To develop and evaluate a method that can fully automatically identify the vessel wall boundaries and quantify the wall thickness for both common carotid artery (CCA) and descending aorta (DAO) from axial magnetic resonance (MR) images. 3T MRI data acquired with T 1 -weighted gradient-echo black-blood imaging sequence from carotid (39 subjects) and aorta (39 subjects) were used to develop and test the algorithm. The vessel wall segmentation was achieved by respectively fitting a 3D cylindrical B-spline surface to the boundaries of lumen and outer wall. The tube-fitting was based on the edge detection performed on the signal intensity (SI) profile along the surface normal. To achieve a fully automated process, Hough Transform (HT) was developed to estimate the lumen centerline and radii for the target vessel. Using the outputs of HT, a tube model for lumen segmentation was initialized and deformed to fit the image data. Finally, lumen segmentation was dilated to initiate the adaptation procedure of outer wall tube. The algorithm was validated by determining: 1) its performance against manual tracing; 2) its interscan reproducibility in quantifying vessel wall thickness (VWT); 3) its capability of detecting VWT difference in hypertensive patients compared with healthy controls. Statistical analysis including Bland-Altman analysis, t-test, and sample size calculation were performed for the purpose of algorithm evaluation. The mean distance between the manual and automatically detected lumen/outer wall contours was 0.00 ± 0.23/0.09 ± 0.21 mm for CCA and 0.12 ± 0.24/0.14 ± 0.35 mm for DAO. No significant difference was observed between the interscan VWT assessment using automated segmentation for both CCA (P = 0.19) and DAO (P = 0.94). Both manual and automated segmentation detected significantly higher carotid (P = 0.016 and P = 0.005) and aortic (P < 0.001 and P = 0.021) wall thickness in the hypertensive patients. A reliable and reproducible pipeline for fully automatic vessel wall quantification was developed and validated on healthy volunteers as well as patients with increased vessel wall thickness. This method holds promise for helping in efficient image interpretation for large-scale cohort studies. 4 J. Magn. Reson. Imaging 2017;45:215-228. © 2016 International Society for Magnetic Resonance in Medicine.

Application of thoracic endovascular aortic repair (TEVAR) in treating dwarfism with Stanford B aortic dissection

PubMed Central

Qiu, Jian; Cai, Wenwu; Shu, Chang; Li, Ming; Xiong, Qinggen; Li, Quanming; Li, Xin

2018-01-01

Abstract Rationale: To apply thoracic endovascular aortic repair (TEVAR) to treat dwarfism complicated with Stanford B aortic dissection. Patient concerns: In this report, we presented a 63-year-old male patient of dwarfism complicated with Stanford B aortic dissection successfully treated with TEVAR. Diagnoses: He was diagnosed with dwarfism complicated with Stanford B aortic dissection. Interventions: After conservative treatment, the male patient underwent TEVAR at 1 week after hospitalization. After operation, he presented with numbness and weakness of his bilateral lower extremities, and these symptoms were significantly mitigated after effective treatment. At 1- and 3-week after TEVAR, the aorta status was maintained stable and restored. Outcomes: The patient obtained favorable clinical prognosis and was smoothly discharged. During subsequent follow-up, he remained physically stable. Lessons: TEVAR is probably an option for treating dwarfism complicated with Stanford B aortic dissection, which remains to be validated by subsequent studies with larger sample size. PMID:29703033

A Methodology for the Derivation of Unloaded Abdominal Aortic Aneurysm Geometry With Experimental Validation

PubMed Central

Chandra, Santanu; Gnanaruban, Vimalatharmaiyah; Riveros, Fabian; Rodriguez, Jose F.; Finol, Ender A.

2016-01-01

In this work, we present a novel method for the derivation of the unloaded geometry of an abdominal aortic aneurysm (AAA) from a pressurized geometry in turn obtained by 3D reconstruction of computed tomography (CT) images. The approach was experimentally validated with an aneurysm phantom loaded with gauge pressures of 80, 120, and 140 mm Hg. The unloaded phantom geometries estimated from these pressurized states were compared to the actual unloaded phantom geometry, resulting in mean nodal surface distances of up to 3.9% of the maximum aneurysm diameter. An in-silico verification was also performed using a patient-specific AAA mesh, resulting in maximum nodal surface distances of 8 μm after running the algorithm for eight iterations. The methodology was then applied to 12 patient-specific AAA for which their corresponding unloaded geometries were generated in 5–8 iterations. The wall mechanics resulting from finite element analysis of the pressurized (CT image-based) and unloaded geometries were compared to quantify the relative importance of using an unloaded geometry for AAA biomechanics. The pressurized AAA models underestimate peak wall stress (quantified by the first principal stress component) on average by 15% compared to the unloaded AAA models. The validation and application of the method, readily compatible with any finite element solver, underscores the importance of generating the unloaded AAA volume mesh prior to using wall stress as a biomechanical marker for rupture risk assessment. PMID:27538124

THE PRESSURE OF AGING

PubMed Central

AlGhatrif, Majd; Wang, Mingyi; Fedorova, Olga V.; Bagrov, Alexei Y.; Lakatta, Edward G.

2016-01-01

Significant hemodynamic changes ensue with aging, leading to an ever-growing epidemic of hypertension. Alterations in central arterial properties play a major role in these hemodynamic changes. These alterations are characterized by an initial decline in aortic distensibility and a rise of diastolic blood pressure, followed by a sharp increase in pulse wave velocity (PWV), and a rise in pulse pressure (PP) beyond the sixth decade. However, the trajectories of PWV and PP diverge with advancing age, more profoundly in men than women, likely reflecting the more pronounced aortic dilatation in men. There is an increased prevalence of salt-sensitive hypertension with advancing age, that is, in part, mediated by marinobufagenin, an endogenous sodium pump ligand, which is also linked to central arterial stiffness. Within the arterial wall, biomechanical and humoral changes are accompanied by significant biomolecular alterations producing a proinflammatory state, in which activation of angiotensin II signaling plays a pivotal role. This proinflammatory state is in origin a reparatory response to a damaged arterial wall under a pulsatile injury. However the same reparatory process results in fibrosis, which in turn worsens arterial stiffness and produce more pulsatile hemodynamics; this relationship between the pulsatile damage and proinflammatory state is best described as a feed-forward loop. Effective efforts to counter the surging epidemic of hypertension with the aging of our population should be aimed at revealing early, pre-clinical hemodynamic and arterial wall alterations, and develop interventions that halt these processes before they reach the stage the medical community defined as “disease”. PMID:27884238

Children and Adolescent Obesity Associates with Pressure-Dependent and Age-Related Increase in Carotid and Femoral Arteries' Stiffness and Not in Brachial Artery, Indicative of Nonintrinsic Arterial Wall Alteration

PubMed Central

García-Espinosa, Victoria; Curcio, Santiago; Castro, Juan Manuel; Arana, Maite; Giachetto, Gustavo; Chiesa, Pedro; Zócalo, Yanina

2016-01-01

Aim. To analyze if childhood obesity associates with changes in elastic, transitional, and/or muscular arteries' stiffness. Methods. 221 subjects (4–15 years, 92 females) were assigned to normal weight (NW, n = 137) or obesity (OB, n = 84) groups, considering their body mass index z-score. Age groups were defined: 4–8; 8–12; 12–15 years old. Carotid, femoral, and brachial artery local stiffness was determined through systodiastolic pressure-diameter and stress-strain relationships. To this end, arterial diameter and peripheral and aortic blood pressure (BP) levels and waveforms were recorded. Carotid-femoral, femoropedal, and carotid-radial pulse wave velocities were determined to evaluate aortic, lower-limb, and upper-limb regional arterial stiffness, respectively. Correlation analysis between stiffness parameters and BP was done. Results. Compared to NW, OB subjects showed higher peripheral and central BP and carotid and femoral stiffness, reaching statistical significance in subjects aged 12 and older. Arterial stiffness differences disappeared when levels were normalized for BP. There were no differences in intrinsic arterial wall stiffness (elastic modulus), BP stiffness relationships, and regional stiffness parameters. Conclusion. OB associates with BP-dependent and age-related increase in carotid and femoral (but not brachial) stiffness. Stiffness changes would not be explained by intrinsic arterial wall alterations but could be associated with the higher BP levels observed in obese children. PMID:27066273

Transesophageal echocardiographic strain imaging predicts aortic biomechanics: Beyond diameter.

PubMed

Emmott, Alexander; Alzahrani, Haitham; Alreishidan, Mohammed; Therrien, Judith; Leask, Richard L; Lachapelle, Kevin

2018-03-11

Clinical guidelines recommend resection of ascending aortic aneurysms at diameters 5.5 cm or greater to prevent rupture or dissection. However, approximately 40% of all ascending aortic dissections occur below this threshold. We propose new transesophageal echocardiography strain-imaging moduli coupled with blood pressure measurements to predict aortic dysfunction below the surgical threshold. A total of 21 patients undergoing aortic resection were recruited to participate in this study. Transesophageal echocardiography imaging of the aortic short-axis and invasive radial blood pressure traces were taken for 3 cardiac cycles. By using EchoPAC (GE Healthcare, Madison, Wis) and postprocessing in MATLAB (MathWorks, Natick, Mass), circumferential stretch profiles were generated and combined with the blood pressure traces. From these data, 2 in vivo stiffness moduli were calculated: the Cardiac Cycle Pressure Modulus and Cardiac Cycle Stress Modulus. From the resected aortic ring, testing squares were isolated for ex vivo mechanical analysis and histopathology. Each square underwent equibiaxial tensile testing to generate stress-stretch profiles for each patient. Two ex vivo indices were calculated from these profiles (energy loss and incremental stiffness) for comparison with the Cardiac Cycle Pressure Modulus and Cardiac Cycle Stress Modulus. The echo-derived stiffness moduli demonstrate positive significant covariance with ex vivo tensile biomechanical indices: energy loss (vs Cardiac Cycle Pressure Modulus: R 2  = 0.5873, P < .0001; vs Cardiac Cycle Stress Modulus: R 2  = 0.6401, P < .0001) and apparent stiffness (vs Cardiac Cycle Pressure Modulus: R 2  = 0.2079, P = .0378; vs Cardiac Cycle Stress Modulus: R 2  = 0.3575, P = .0042). Likewise, these transesophageal echocardiography-derived moduli are highly predictive of the histopathologic composition of collagen and elastin (collagen/elastin ratio vs Cardiac Cycle Pressure Modulus: R 2  = 0.6165, P < .0001; vs Cardiac Cycle Stress Modulus: R 2  = 0.6037, P < .0001). Transesophageal echocardiography-derived stiffness moduli correlate strongly with aortic wall biomechanics and histopathology, which demonstrates the added benefit of using simple echocardiography-derived biomechanics to stratify patient populations. Copyright © 2018. Published by Elsevier Inc.

Acute aortic dissection involving the root: operative and long-term outcome after curative proximal repair†

PubMed Central

Urbanski, Paul P.; Lenos, Aristidis; Irimie, Vadim; Bougioukakis, Petros; Zacher, Michael; Diegeler, Anno

2016-01-01

OBJECTIVES The aim of the study was to evaluate operative and long-term results after surgery of acute aortic dissection involving the root, in which the proximal repair consisted of curative resection of all dissected aortic sinuses and was performed using either valve-sparing root repair or complete root replacement with a valve conduit. METHODS Between August 2002 and March 2013, 162 consecutive patients (mean age 63 ± 14 years) underwent surgery for acute type A aortic dissection. Eighty-six patients with an involvement of the aortic root underwent curative surgery of the proximal aorta consisting of valve-sparing root repair (n = 54, 62.8%) or complete valve and root replacement using composite valve grafts (n = 32, 37.2%). In patients with root repair, all dissected aortic walls were resected and root remodelling using the single patch technique (n = 53) or root repair with valve reimplantation (n = 1) was performed without the use of any glue. All perioperative data were collected prospectively and retrospective statistical examination was performed using univariate and multivariate analyses. RESULTS The mean follow-up was 5.2 ± 3.5 years for all patients (range 0–12 years) and 6.1 ± 3.3 years for survivors. The 30-day mortality rate was 5.8% (5 patients), being considerably lower in the repair sub-cohort (1.9 vs 12.5%). The estimated survival rate at 5 and 10 years was 80.0 ± 4.5 and 69.1 ± 6.7%, respectively. No patient required reoperation on the proximal aorta and/or aortic valve during the follow-up time and there were only two valve-related events (both embolic, one in each group). Among those patients with repaired valves, the last echocardiography available showed no insufficiency in 40 and an irrelevant insufficiency (1+) in 14. CONCLUSIONS Curative repair of the proximal aorta in acute dissection involving the root provides favourable operative and long-term outcome with very low risk of aortic complications and/or reoperations, regardless if a valve-sparing procedure or replacement with a valve conduit is used. Valve-sparing surgery is frequently suitable, providing excellent outcome and very high durability. PMID:26848190

Full dimensional computer simulations to study pulsatile blood flow in vessels, aortic arch and bifurcated veins: Investigation of blood viscosity and turbulent effects.

PubMed

Sultanov, Renat A; Guster, Dennis

2009-01-01

We report computational results of blood flow through a model of the human aortic arch and a vessel of actual diameter and length. A realistic pulsatile flow is used in all simulations. Calculations for bifurcation type vessels are also carried out and presented. Different mathematical methods for numerical solution of the fluid dynamics equations have been considered. The non-Newtonian behaviour of the human blood is investigated together with turbulence effects. A detailed time-dependent mathematical convergence test has been carried out. The results of computer simulations of the blood flow in vessels of three different geometries are presented: for pressure, strain rate and velocity component distributions we found significant disagreements between our results obtained with realistic non-Newtonian treatment of human blood and the widely used method in the literature: a simple Newtonian approximation. A significant increase of the strain rate and, as a result, the wall shear stress distribution, is found in the region of the aortic arch. Turbulent effects are found to be important, particularly in the case of bifurcation vessels.

The Effect of Aortic Compliance on Left Ventricular Power Requirement

NASA Astrophysics Data System (ADS)

Pahlevan, Niema; Gharib, Morteza

2009-11-01

Aortic compliance depends on both geometry and mechanical properties of the aorta. Reduction in arterial compliance has been associated with aging, smoking, and multiple cardiovascular diseases. Increased stiffness of the aorta affects the wave dynamics in the aorta by increasing both pulse pressure amplitude and wave speed. We hypothesized that decreased aortic compliance leads to an increased left ventricular power requirement for a fixed cardiac output due to altered pulse pressure and pulse wave velocity. We used a computational approach using the finite element method for solid and fluid domains coupled to each other by using the direct coupling method. A nonlinear material model was used for the solid wall. The fluid flow model was considered to be Newtonian, incompressible, and laminar. The simulation was performed for a heart rate of 75 beats per minute for six different compliances while keeping the cardiac output and the peripheral resistance constant. The results show a trend towards increased left ventricular energy expenditure per cycle with decreased compliance. The relevance of these findings to clinical observations will be discussed.

Flexible robotic catheters in the visceral segment of the aorta: advantages and limitations.

PubMed

Li, Mimi M; Hamady, Mohamad S; Bicknell, Colin D; Riga, Celia V

2018-06-01

Flexible robotic catheters are an emerging technology which provide an elegant solution to the challenges of conventional endovascular intervention. Originally developed for interventional cardiology and electrophysiology procedures, remotely steerable robotic catheters such as the Magellan system enable greater precision and enhanced stability during target vessel navigation. These technical advantages facilitate improved treatment of disease in the arterial tree, as well as allowing execution of otherwise unfeasible procedures. Occupational radiation exposure is an emerging concern with the use of increasingly complex endovascular interventions. The robotic systems offer an added benefit of radiation reduction, as the operator is seated away from the radiation source during manipulation of the catheter. Pre-clinical studies have demonstrated reduction in force and frequency of vessel wall contact, resulting in reduced tissue trauma, as well as improved procedural times. Both safety and feasibility have been demonstrated in early clinical reports, with the first robot-assisted fenestrated endovascular aortic repair in 2013. Following from this, the Magellan system has been used to successfully undertake a variety of complex aortic procedures, including fenestrated/branched endovascular aortic repair, embolization, and angioplasty.

Erythropoietin has an antiapoptotic effect after myocardial infarction and stimulates in vitro aortic ring sprouting

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

Mansson Broberg, Agneta; Grinnemo, Karl-Henrik; Genead, Rami

Aims were to explore if darbepoietin-{alpha} in mouse can induce angiogenesis and if moderate doses after myocardial infarction stimulates periinfarct capillary and arteriolar densities, cell proliferation, and apoptosis. Myocardial infarction was induced by ligation of LAD. Mouse aortic rings (0.8 mm) were cultured in matrigel and the angiogenic sprouting was studied after addition of darbepoietin-{alpha} with and without VEGF-165. After 12 days the hemoglobin concentration was 25% higher in the darbepoietin-{alpha} treated mice than in the control group. No difference in capillary densities in the periinfarct or noninfarcted areas was seen with darbepoietin-{alpha}. Cell proliferation was about 10 times highermore » in the periinfarct area than in the noninfarcted wall. Darbepoietin-{alpha} treatment led to a decrease of cell proliferation (BrdU, (p < 0.02)) and apoptosis (TUNEL, p < 0.005) with about 30% in the periinfarct area. Darbepoietin-{alpha} and VEGF-165 both independently induced sprouting from aortic rings. The results suggest that darbepoietin-{alpha} can induce angiogenesis but that moderate doses after myocardial infarction are not angiogenic but antiapoptotic.« less

TAVR Through Heavily Calcified Aorta Following Atheroma Retrieval With the "Elevator" Technique.

PubMed

Senguttuvan, N Boopathy; Ellozy, Sharif; Tejani, Furqan; Kovacic, Jason; Kini, Annapoorna S; Sharma, Samin K; Dangas, George D

2015-10-01

An 86-year-old Caucasian female with severe symptomatic, inoperable aortic stenosis was accepted for high-risk transfemoral transcatheter aortic valve replacement (TAVR) approach due to severe calcification of the aorta. During initial passage of a 22 Fr sheath, there was dislodgment with proximal migration of a circumferential tunnel of calcium from the infrarenal aorta. A novel "elevator" technique was used to secure and retrieve the dislodged aorta en bloc back to its original infrarenal aortic position and allow in situ fixation with stenting. A new TAVR system was then successfully placed through the stent and a 23 mm Edwards Sapien valve (Edwards Lifesciences) was implanted as planned. In case of calcification protruding into the lumen of the aorta and limiting the passage of the large valve delivery system sheath, the obstruction can be managed by stenting the calcification against the luminal wall under fluoroscopic and intravascular-ultrasound guidance, allowing successful passage of the valve delivery system. The elevator technique allows axial transportation of any calcified vascular fragments, should they become dislodged.

A mathematical model of aortic aneurysm formation

PubMed Central

Hao, Wenrui; Gong, Shihua; Wu, Shuonan; Xu, Jinchao; Go, Michael R.; Friedman, Avner; Zhu, Dai

2017-01-01

Abdominal aortic aneurysm (AAA) is a localized enlargement of the abdominal aorta, such that the diameter exceeds 3 cm. The natural history of AAA is progressive growth leading to rupture, an event that carries up to 90% risk of mortality. Hence there is a need to predict the growth of the diameter of the aorta based on the diameter of a patient’s aneurysm at initial screening and aided by non-invasive biomarkers. IL-6 is overexpressed in AAA and was suggested as a prognostic marker for the risk in AAA. The present paper develops a mathematical model which relates the growth of the abdominal aorta to the serum concentration of IL-6. Given the initial diameter of the aorta and the serum concentration of IL-6, the model predicts the growth of the diameter at subsequent times. Such a prediction can provide guidance to how closely the patient’s abdominal aorta should be monitored. The mathematical model is represented by a system of partial differential equations taking place in the aortic wall, where the media is assumed to have the constituency of an hyperelastic material. PMID:28212412

Suprasternal notch echocardiography: a potential alternative for the measurement of respiratory variation in aortic blood flow peak velocity in mechanically ventilated children.

PubMed

Devauchelle, Pauline; de Queiroz Siqueira, Mathilde; Lilot, Marc; Chassard, Dominique; Desgranges, François-Pierrick

2018-06-01

We conducted a prospective, observational study to investigate the relationship between the respiratory variation in aortic blood flow peak velocity (ΔVPeak) measured by echocardiography in the proximal ascending aorta from the suprasternal notch window and the ΔVPeak measured at the level of the aortic annulus from the classical apical five-chamber view. We studied children aged from 1 to 10 years referred for surgery under general anesthesia with positive pressure ventilation, after induction of general anesthesia. Twenty-two children (mean age = 5 ± 3 years) were recruited. There was a significant relationship between the ΔVPeak recorded via the suprasternal notch view and the ΔVPeak recorded via the apical five-chamber view (r = 0.62 [95% confidence interval 0.25-0.84], P = 0.003). The ΔVPeak measured using the suprasternal notch route could be considered to predict fluid responsiveness in children under mechanical ventilation, notably when the access to the chest wall is limited during surgery.

Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate

PubMed Central

Ivanov, Vadim; Ivanova, Svetlana; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

2016-01-01

Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth muscle cells, assayed by measuring intracellular collagen content. We observed increased intracellular levels of ascorbate under supplementation with elevated doses of ascorbic acid, as well as its lipid soluble derivative ascorbyl palmitate. Nifedipine reduced ascorbic acid intracellular influx in cultured aortic smooth muscle cells with nifedipine (50 µM) compared to control. Adverse effects of nifedipine were neutralized either by an increased level of cell supplementation with ascorbic acid or by substituting it with ascorbyl palmitate. These studies suggest that adverse effects of channel blockers could be caused by their weakening the arterial wall integrity by interfering with proper extracellular matrix formation. In conclusion, these studies confirm the adverse effects of channel blockers on collagen type l and lV deposition, the key ECM components essential for maintaining optimal structural integrity of the arterial walls. Ascorbate supplementation reversed channel blocker inhibition of these collagen types synthesis and deposition. The results of this study imply the benefits of ascorbate and ascorbate palmitate supplementation in medical management of cardiovascular disease in order to compensate for adverse effects of channel blockers. PMID:27335688

Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate.

PubMed

Ivanov, Vadim; Ivanova, Svetlana; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

2016-01-01

Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth muscle cells, assayed by measuring intracellular collagen content. We observed increased intracellular levels of ascorbate under supplementation with elevated doses of ascorbic acid, as well as its lipid soluble derivative ascorbyl palmitate. Nifedipine reduced ascorbic acid intracellular influx in cultured aortic smooth muscle cells with nifedipine (50 µM) compared to control. Adverse effects of nifedipine were neutralized either by an increased level of cell supplementation with ascorbic acid or by substituting it with ascorbyl palmitate. These studies suggest that adverse effects of channel blockers could be caused by their weakening the arterial wall integrity by interfering with proper extracellular matrix formation. In conclusion, these studies confirm the adverse effects of channel blockers on collagen type l and lV deposition, the key ECM components essential for maintaining optimal structural integrity of the arterial walls. Ascorbate supplementation reversed channel blocker inhibition of these collagen types synthesis and deposition. The results of this study imply the benefits of ascorbate and ascorbate palmitate supplementation in medical management of cardiovascular disease in order to compensate for adverse effects of channel blockers.

Supersonic minimum length nozzle design for dense gases

NASA Technical Reports Server (NTRS)

Aldo, Andrew C.; Argrow, Brian M.

1993-01-01

Recently, dense gases have been investigated for many engineering applications such as for turbomachinery and wind tunnels. Supersonic nozzle design for these gases is complicated by their nonclassical behavior in the transonic flow regime. In this paper a method of characteristics (MOC) is developed for two-dimensional (planar) and, primarily, axisymmetric flow of a van der Waals gas. Using a straight aortic line assumption, a centered expansion is used to generate an inviscid wall contour of minimum length. The van der Waals results are compared to previous perfect gas results to show the real gas effects on the flow properties and inviscid wall contours.

Echocardiographic reference ranges for sedentary donkeys in the UK.

PubMed

Roberts, S L; Dukes-McEwan, J

2016-10-01

The aim of this study was to provide two-dimensional (2D) and M-mode echocardiographic reference ranges from a sample of the UK population of donkeys including geriatrics (>30 years), owned by The Donkey Sanctuary, and to assess the influence of gender, weight and age on these variables. A total of 36 donkeys with no clinical or echocardiographic evidence of cardiovascular disease were examined; 24 geldings and 12 females, aged 3-45 years old, weighing 130-262 kg. Left atrial to aortic ratio was larger in geldings (P=0.004). There was no significant difference for left ventricular M-mode diastolic diameter between females and geldings (P=0.121) after exclusion of one heavy female outlier. 2D measurements significantly increased with bodyweight including maximal left atrial diameter (R(2)=0.112; P=0.046), aortic diameter at various levels (e.g. annulus: R(2)=0.35; P<0.001) and the pulmonary artery diameter (R(2)=0.124; P=0.035). M-mode measurements were not significantly influenced by weight other than the left ventricular free wall in systole (R(2)=0.118; P=0.041). Age and heart rate did not have any significant effect on echocardiographic variables. This is the first UK study to report on echocardiographic reference ranges of sedentary donkeys across a wide age range and shows differences compared with reference ranges from working donkeys. British Veterinary Association.

Efficacy of the Stonehenge Technique for Minimally Invasive Aortic Valve Replacement via Right Infraaxillary Thoracotomy.

PubMed

Yamazaki, Masataka; Kin, Hajime; Kitamoto, Shohei; Yamanaka, Shota; Nishida, Hidefumi; Nishigawa, Kosaku; Takanashi, Shuichiro

2017-02-20

Minimally invasive cardiac surgeries for aortic valve replacement (AVR) are still a technical challenge for surgeons because these procedures are undertaken through small incisions and deep surgical fields. Although AVR via vertical infraaxillary thoracotomy can be a cosmetically superior option, a disadvantage of this approach is the distance between the thoracotomy incision and the ascending aorta. Therefore, we devised a technique to perform all manipulations using the fingertips without the aid of a knot pusher or long-shafted surgical instruments. This was achieved by particular placement of several retracted sutures to the right chest wall. We named placement of these sutures the "Stonehenge technique." In conclusion, AVR via vertical infraaxillary thoracotomy with our Stonehenge technique can be safely and simply performed with superior cosmetic advantages.

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

Cheng, Lik Fai, E-mail: rickieclf@yahoo.com.hk; Cheung, Kwok Fai; Chan, Kwong Man

Nellix Endovascular Aneurysm Sealing (EVAS) system is a new concept and technology of abdominal aortic aneurysm (AAA) repair. Elective EVAS using Nellix device was performed for a 83-year-old man with AAA. 2-month post-EVAS CTA surveillance demonstrated mild enlargement of aneurysmal sac and separation of the EndoBags, but without detectable endoleak. The patient developed sudden AAA rupture with retroperitoneal hematoma at about 4 months after EVAS. We postulated that early enlargement of aneurysmal sac and separation of EndoBags of Nellix devices after EVAS, even without detectable endoleak, might indicate significant aneurysmal wall weakening with increased risk of later AAA rupture. To themore » best of the authors’ knowledge, this was the first reported case of aortic rupture after EVAS without detectable endoleak during and after the procedure.« less

Novel experimental model of pressure overload hypertrophy in rats.

PubMed

Molina, Ezequiel J; Gupta, Dipin; Palma, Jon; Torres, Denise; Gaughan, John P; Houser, Steven; Macha, Mahender

2009-05-15

We studied a novel animal model of pressure overload hypertrophy in transition to heart failure following ascending aortic constriction. We sought to assess chronologic changes in hemodynamic parameters, echocardiographic signs of left ventricular (LV) remodeling, exercise tolerance, and profiles of systemic and local inflammation. A cohort of Sprague Dawley rats underwent aortic constriction proximal to the innominate artery and were followed by echocardiography. A group of animals were euthanized 20 wk after aortic constriction, before any detectable decline in fractional shortening (normal fractional shortening (FS) or control group; n = 6). When additional animals reached an absolute 25% decline in fractional shortening, they were randomized to be euthanized on d 0 (25% downward arrow FS group; n = 5), or d 21 (>25% downward arrow FS group; n = 6). Hemodynamic and echocardiographic assessment, swim testing to exhaustion, and measurement of systemic and local inflammatory markers was performed at each time interval. An absolute decline of 25% in FS after aortic constriction was observed between 24 and 28 wk for most animals. The transition from compensated to decompensated hypertrophy was associated with markedly decreased dP/dt(max) and dP/dt(min), increased LV end-systolic diameter and LV end-diastolic diameter, stabilization of LV free wall diameter, decreased exercise performance and up-regulation in expression of interleukin-1, interleukin-6, tumor necrosis factor-alpha, and atrial natriuretic peptide. All animals developed heart failure. This study demonstrates that proximal aortic constriction in young rats represents an excellent experimental model of pressure overload hypertrophy that may be useful for testing the efficacy of novel therapies for the treatment of heart failure.

Structure of the Elastin-Contractile Units in the Thoracic Aorta and How Genes That Cause Thoracic Aortic Aneurysms and Dissections Disrupt This Structure.

PubMed

Karimi, Ashkan; Milewicz, Dianna M

2016-01-01

The medial layer of the aorta confers elasticity and strength to the aortic wall and is composed of alternating layers of smooth muscle cells (SMCs) and elastic fibres. The SMC elastin-contractile unit is a structural unit that links the elastin fibres to the SMCs and is characterized by the following: (1) layers of elastin fibres that are surrounded by microfibrils; (2) microfibrils that bind to the integrin receptors in focal adhesions on the cell surface of the SMCs; and (3) SMC contractile filaments that are linked to the focal adhesions on the inner side of the membrane. The genes that are altered to cause thoracic aortic aneurysms and aortic dissections encode proteins involved in the structure or function of the SMC elastin-contractile unit. Included in this gene list are the genes encoding protein that are structural components of elastin fibres and microfibrils, FBN1, MFAP5, ELN, and FBLN4. Also included are genes that encode structural proteins in the SMC contractile unit, including ACTA2, which encodes SMC-specific α-actin and MYH11, which encodes SMC-specific myosin heavy chain, along with MYLK and PRKG1, which encode kinases that control SMC contraction. Finally, mutations in the gene encoding the protein linking integrin receptors to the contractile filaments, FLNA, also predispose to thoracic aortic disease. Thus, these data suggest that functional SMC elastin-contractile units are important for maintaining the structural integrity of the aorta. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds

PubMed Central

Hockaday, L A; Kang, K H; Colangelo, N W; Cheung, P Y C; Duan, B; Malone, E; Wu, J; Girardi, L N; Bonassar, L J; Lipson, H; Chu, C C; Butcher, J T

2013-01-01

The aortic valve exhibits complex three-dimensional (3D) anatomy and heterogeneity essential for long-term efficient biomechanical function. These are, however, challenging to mimic in de novo engineered living tissue valve strategies. We present a novel simultaneous 3D-printing/photocrosslinking technique for rapidly engineering complex, heterogeneous aortic valve scaffolds. Native anatomic and axisymmetric aortic valve geometries (root wall and tri-leaflets) with 12 to 22 mm inner diameters (ID) were 3D printed with poly-ethylene glycol-diacrylate (PEG-DA) hydrogels (700 or 8000 MW) supplemented with alginate. 3D printing geometric accuracy was quantified and compared using Micro-CT. Porcine aortic valve interstitial cells (PAVIC) seeded scaffolds were cultured for up to 21 days. Results showed that blended PEG-DA scaffolds could achieve over 10-fold range in elastic modulus (5.3±0.9 to 74.6±1.5 kPa). 3D printing times for valve conduits with mechanically contrasting hydrogels were optimized to 14 to 45 minutes, increasing linearly with conduit diameter. Larger printed valves had greater shape fidelity (93.3±2.6, 85.1±2.0, and 73.3±5.2% for 22, 17, and 12 mm ID porcine valves; 89.1±4.0, 84.1±5.6, and 66.6±5.2% for simplified valves). PAVIC seeded scaffolds maintained near 100% viability over 21 days. These results demonstrate that 3D hydrogel printing with controlled photocrosslinking can rapidly fabricate anatomical heterogeneous valve conduits that support cell engraftment. PMID:22914604

In-vivo assessment of the morphology and hemodynamic functions of the BioValsalva™ composite valve-conduit graft using cardiac magnetic resonance imaging and computational modelling technology.

PubMed

Kidher, Emaddin; Cheng, Zhuo; Jarral, Omar A; O'Regan, Declan P; Xu, Xiao Yun; Athanasiou, Thanos

2014-12-09

The evaluation of any new cardiac valvular prosthesis should go beyond the classical morbidity and mortality rates and involve hemodynamic assessment. As a proof of concept, the objective of this study was to characterise for the first time the hemodynamics and the blood flow profiles at the aortic root in patients implanted with BioValsalva™ composite valve-conduit using comprehensive MRI and computer technologies. Four male patients implanted with BioValsalva™ and 2 age-matched normal controls (NC) underwent cardiac magnetic resonance imaging (MRI). Phase-contrast imaging with velocity-mapping in 3 orthogonal directions was performed at the level of the aortic root and descending thoracic aorta. Computational fluid dynamic (CFD) simulations were performed for all the subjects with patient-specific flow information derived from phase-contrast MR data. The maximum and mean flow rates throughout the cardiac cycle at the aortic root level were very comparable between NC and BioValsalva™ patients (541 ± 199 vs. 567 ± 75 ml/s) and (95 ± 46 vs. 96 ± 10 ml/s), respectively. The maximum velocity (cm/s) was higher in patients (314 ± 49 vs. 223 ± 20; P = 0.06) due to relatively smaller effective orifice area (EOA), 2.99 ± 0.47 vs. 4.40 ± 0.24 cm2 (P = 0.06), however, the BioValsalva™ EOA was comparable to other reported prosthesis. The cross-sectional area and maximum diameter at the root were comparable between the two groups. BioValsalva™ conduit was stiffer than the native aortic wall, compliance (mm2 • mmHg(-1) • 10(-3)) values were (12.6 ± 4.2 vs 25.3 ± 0.4.; P = 0.06). The maximum time-averaged wall shear stress (Pa), at the ascending aorta was equivalent between the two groups, 17.17 ± 2.7 (NC) vs. 17.33 ± 4.7 (BioValsalva™ ). Flow streamlines at the root and ascending aorta were also similar between the two groups apart from a degree of helical flow that occurs at the outer curvature at the angle developed near the suture line. BioValsalva™ composite valve-conduit prosthesis is potentially comparable to native aortic root in structural design and in many hemodynamic parameters, although it is stiffer. Surgeons should pay more attention to the surgical technique to maximise the reestablishment of normal smooth aortic curvature geometry to prevent unfavourable flow characteristics.

Decellularized heart valve as a scaffold for in vivo recellularization: deleterious effects of granulocyte colony-stimulating factor.

PubMed

Juthier, Francis; Vincentelli, André; Gaudric, Julien; Corseaux, Delphine; Fouquet, Olivier; Calet, Christine; Le Tourneau, Thierry; Soenen, Valérie; Zawadzki, Christophe; Fabre, Olivier; Susen, Sophie; Prat, Alain; Jude, Brigitte

2006-04-01

Autologous recellularization of decellularized heart valve scaffolds is a promising challenge in the field of tissue-engineered heart valves and could be boosted by bone marrow progenitor cell mobilization. The aim of this study was to examine the spontaneous in vivo recolonization potential of xenogeneic decellularized heart valves in a lamb model and the effects of granulocyte colony-stimulating factor mobilization of bone marrow cells on this process. Decellularized porcine aortic valves were implanted in 12 lambs. Six lambs received granulocyte colony-stimulating factor (10 microg x kg(-1) x d(-1) for 7 days, granulocyte colony-stimulating factor group), and 6 received no granulocyte colony-stimulating factor (control group). Additionally, nondecellularized porcine valves were implanted in 5 lambs (xenograft group). Angiographic and histologic evaluation was performed at 3, 6, 8, and 16 weeks. Few macroscopic modifications of leaflets and the aortic wall were observed in the control group, whereas progressive shrinkage and thickening of the leaflets appeared in the granulocyte colony-stimulating factor and xenograft groups. In the 3 groups progressive ovine cell infiltration (fluorescence in situ hybridization) was observed in the leaflets and in the adventitia and the intima of the aortic wall but not in the media. Neointimal proliferation of alpha-actin-positive cells, inflammatory infiltration, adventitial neovascularization, and calcifications were more important in the xenograft and the granulocyte colony-stimulating factor groups than in the control group. Continuous re-endothelialization appeared only in the control group. Decellularized xenogeneic heart valve scaffolds allowed partial autologous recellularization. Granulocyte colony-stimulating factor led to accelerated heart valve deterioration similar to that observed in nondecellularized xenogeneic cardiac bioprostheses.

Regional distribution of circumferential residual strains in the human aorta according to age and gender.

PubMed

Sokolis, Dimitrios P; Savva, Giannis D; Papadodima, Stavroula A; Kourkoulis, Stavros K

2017-03-01

The biomechanical response of the human aorta varies with axial location, but little is known about the respective variation of residual strains. Such data are available for common lab animals, but in the traditional opening angle measurement the aorta is considered as an ideal cylinder and average residual strains are measured, so that the spatial variations of local residual strains are not determined. The present study provides opening angle and residual strain data throughout the course and around the circumference of the aorta harvested during autopsy. Opening angle showed notable topographical variation; the highest value was at the top of aortic arch, declining abruptly toward the ascending aorta and to a near-constant value in the descending aorta, and rising in the abdominal aorta. The variation of curvature and of external but not internal residual stretch resembled that of opening angle. Extensive residual stress and wall thickness differences were evidenced among quadrants, with the more pre-stressed being also the thicker quadrants. Gender had overall minor effects, but aging led to increased parameters, occurring earlier in the distal aorta but at later stages becoming predominant proximally. Differences in caliber were pronounced in older subjects, unlike those in opening angle, residual stretches, and thickness that were striking in middle-aged subjects. By contrast, curvature decreased with aging in relation to the smaller percentwise opening angle differences. Detailed knowledge of the zero-stress/no-load geometry of the human aortic wall is critical for an in-depth understanding of aortic physiology, while providing the basis for comparison with disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Stenting of aortic coarctation: acute, intermediate, and long-term results of a prospective multi-institutional registry--Congenital Cardiovascular Interventional Study Consortium (CCISC).

PubMed

Holzer, Ralf; Qureshi, Shakeel; Ghasemi, Abdolrahim; Vincent, Julie; Sievert, Horst; Gruenstein, Daniel; Weber, Howard; Alday, Luis; Peirone, Alejandro; Zellers, Thomas; Cheatham, John; Slack, Michael; Rome, Jonathan

2010-10-01

Since the 1980s, stent implantation has evolved as an important therapeutic strategy for coarctation of the aorta. However, available data is frequently flawed by short follow-up, lack of adequate follow-up imaging, and retrospective nature of data collection. Data was prospectively collected using a multicenter registry congenital cardiovascular interventional study consortium (CCISC). Between 2000 and 2009, 302 patients from 34 centers with a median weight of 58 kg underwent stent implantation for coarctation. Eligible patients (44%) completed intermediate follow-up (3-18 months) with integrated imaging (cath, CT, MRI), whereas 21% completed long-term follow-up (>18-60 months). Procedural success was defined as UL/LL systolic gradient of less than 20 mm Hg, lack of significant recurrent obstruction, and freedom from unplanned repeat intervention. Acute procedural success was 96%. Cumulative intermediate success was 86%, and cumulative long-term success was 77%. Unplanned repeat interventions were required in 4%, and aortic wall complications were seen in 1% of patients (dissection n = 1 and aneurysm n = 3). Other adverse events (n = 15) occurred mainly acutely and included technical complications such as stent malposition (n = 9). At long-term follow-up, 23% of patients continued to have systolic blood pressure above the 95th centile, 9% had an upper-to-lower limb blood pressure gradient in excess of 20 mm Hg, and 32% were taking antihypertensive medication. This study documented acute, intermediate, and long-term outcome data comparable or superior with other surgical or interventional series. However, even with successful initial stent therapy, patients continue to require long-term follow-up and have associated long-term morbidity, relating to aortic wall complications, systemic hypertension, recurrent obstruction as well as need for repeat intervention. © 2010 Wiley-Liss, Inc.

The complementary role of magnetic resonance imaging, Doppler echocardiography, and computed tomography in the diagnosis of dissecting thoracic aneurysms.

PubMed

Goldman, A P; Kotler, M N; Scanlon, M H; Ostrum, B; Parameswaran, R; Parry, W R

1986-05-01

Non-ECG gated MRI was compared with 2DE and/or CT scans in 10 patients with dissecting aneurysms proven by angiography and/or surgery. Patient ages ranged from 48 to 85 years (mean 69.6). Six had DeBakey type I dissections and four had DeBakey type III dissections. MRI was diagnostic for aortic dissection in nine cases and suggestive in the tenth. 2DE was diagnostic in six out of nine patients, suggestive in two patients, and nondiagnostic in one patient. CT was diagnostic in the three cases in which it was employed. MRI demonstrated a dilated ascending aorta with thickened walls in all type I dissections as well as an intimal flap and slow flow in the false channel in four patients. In the other two patients with type I dissection, MRI detected the intimal flap in the descending aorta but not in the ascending aorta, whereas 2DE revealed the ascending aortic intimal flap in both of these patients and CT showed it in one of them. In the type III dissections, MRI demonstrated a thickened wall and thrombus in the lumen in all four cases, and the intimal flap in three out of the four. 2DE excluded ascending aortic involvement in all three type III dissections. Six other patients with fusiform dilated ascending aortas had no evidence of dissection by MRI, 2DE, and aortography. Thus, non-ECG gated MRI alone or in combination with 2DE and/or CT is useful in the diagnosis of dissecting thoracic aneurysm and in assessing the extent of the dissection. In addition, the differentiation of dissecting aneurysms of the aorta from fusiform dilatation of the aorta is made possible by these noninvasive techniques.

Relations of Central Hemodynamics and Aortic Stiffness with Left Ventricular Structure and Function: The Framingham Heart Study.

PubMed

Kaess, Bernhard M; Rong, Jian; Larson, Martin G; Hamburg, Naomi M; Vita, Joseph A; Cheng, Susan; Aragam, Jayashree; Levy, Daniel; Benjamin, Emelia J; Vasan, Ramachandran S; Mitchell, Gary F

2016-03-25

The differing relations of steady and pulsatile components of central hemodynamics and aortic stiffness with cardiac dimensions and function have not been fully elucidated. Central hemodynamics and carotid-femoral pulse wave velocity (CFPWV, a measure of aortic stiffness) were measured by arterial tonometry in 5799 participants of the Framingham Heart Study (mean age 51 years, 54% women) and related to echocardiographic left ventricular (LV) dimensions and systolic and diastolic function using multivariable-adjusted partial Pearson correlations. Mean arterial pressure (MAP, steady component of central blood pressure) was associated positively with LV wall thickness (r=0.168; P<0.0001) but showed only a weak direct association with LV diastolic dimension (r=0.035, P=0.006). Central pulse pressure (pulsatile component of central blood pressure) showed a direct correlation with both LV diastolic dimension and LV wall thickness (r=0.08 and 0.044, both P<0.0001 in multivariable models that included MAP). CFPWV was not associated with LV structure (all P≥0.27) in MAP-adjusted models). Both MAP and CFPWV were associated inversely with LV diastolic function (E'; r=-0.140 and -0.153, respectively; both P<0.0001), and these associations persisted after additional adjustment for LV mass and central pulse pressure (r=-0.142 and -0.108, both P<0.0001). MAP and CFPWV were not associated with LV fractional shortening (P≥0.10), whereas central pulse pressure was positively related (r=0.064, P<0.0001). Pulsatile and steady components of central pressure are conjointly yet variably related to LV structure. CFPWV is related to LV diastolic function but not to systolic function. Additional studies are warranted to confirm these observations. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Increased interleukin-11 levels in thoracic aorta and plasma from patients with acute thoracic aortic dissection.

PubMed

Xu, Yao; Ye, Jing; Wang, Menglong; Wang, Yuan; Ji, Qingwei; Huang, Ying; Zeng, Tao; Wang, Zhen; Ye, Di; Jiang, Huimin; Liu, Jianfang; Lin, Yingzhong; Wan, Jun

2018-06-01

Interleukin (IL) 11 is closely related to tumor and hematological system diseases. Recent studies have demonstrated that IL-11 also participates in cardiovascular diseases, including ischemia-reperfusion mediated heart injury and acute myocardial infarction. This study aimed to investigate whether IL-11 is involved in acute thoracic aortic dissection (TAD). Aortic tissue samples from normal donors and acute TAD patients were collected, and the expression of IL-11 in all aortic tissue was analyzed. In addition, blood samples from patients with chest pain were collected and divided into a non-AD (NAD) group and a TAD group according to the results of computed tomography angiography of the thoracic aorta. The plasma IL-11, IL-17 and interferon (IFN) γ in all blood samples were measured. Compared with aortic tissue of normal controls, IL-11 was significantly increased in aortic tissue of acute TAD patients, especially in the torn section. The IL-11 was derived from aorta macrophages in TAD. In addition, the plasma IL-11, IL-17 and IFN-γ were significantly higher in acute TAD patients than in NAD patients, and the correlation analysis showed that IL-11 levels were positively correlated with levels of IFN-γ, IL-17, glucose, systolic blood pressure, diastolic blood pressure, white blood cells, C-reactive proteins and D-dimers. Binary logistic regression analyses showed that elevated IL11 in patients who may have diagnostic value of TAD, but less that D-dimer. IL-11 was increased in thoracic aorta and plasma of TAD patients and may be a promising biomarker for diagnosis in patients with TAD. Copyright © 2018. Published by Elsevier B.V.

Deformation Differences between Tricuspid and Bicuspid Aortic Valves in Vitro

NASA Astrophysics Data System (ADS)

Szeto, Kai; Rodriguez-Rodriguez, Javier; Pastuszko, Peter; Nigam, Vishal; Lasheras, Juan C.

2011-11-01

It has been shown in clinical studies that patients with congenital bicuspid aortic valves (CBAVs) develop degenerative calcification of the leaflets at young ages compared to patients with the normal tricuspid aortic valves (TAVs). It has been hypothesized that the asymmetrical geometry of the leaflets in CBAVs, flow shear stresses (SS), disturbed flow, and excessive strain rate levels are possible causes for the early calcification and stenosis. Central to the validation of this hypothesis is the need to quantify the differences in strain rate levels between the BAVs and TAVs. We simulate the CBAVs by surgically stitching two of the leaflets of a porcine aortic valve together. To quantify strain differences, we performed in-vitro experiments in both trileaflet and bileaflet valves by tracking the motion of small ink dots marked on each leaflet surface. We then used phase-locked stereo photogrammetry to reconstruct at each instant of time the 3D surface of the leaflets and measure the strain rates in both radial and circumferential directions during the whole cardiac cycle. Our results indicate that the total strain rate of the simulated BAVs is about 15 to 20% higher than the normal leaflets of TAVs at systole. In the BAVs' case, the fused leaflet stretches radially up to 25% higher than the reference length. The excessive stretching in both directions in the fused leaflet results in large changes in the flow patterns and associated wall SS.

Astragaloside IV Attenuated 3,4-Benzopyrene-Induced Abdominal Aortic Aneurysm by Ameliorating Macrophage-Mediated Inflammation.

PubMed

Wang, Jiaoni; Zhou, Yingying; Wu, Shaoze; Huang, Kaiyu; Thapa, Saroj; Tao, Luyuan; Wang, Jie; Shen, Yigen; Wang, Jinsheng; Xue, Yangjing; Ji, Kangting

2018-01-01

Abdominal aortic aneurysm (AAA), characterized by macrophage infiltration-mediated inflammation and oxidative stress, is a potentially fatal disease. Astragaloside IV (AS-IV) has been acknowledged to exhibit antioxidant and anti-inflammatory properties. This study was designed to investigate the protective effect of AS-IV against AAA formation induced by 3,4-benzopyrene (Bap) and angiotensin II (Ang II), and to explore probable mechanisms. Results showed that AS-IV decreased AAA formation, and reduced macrophage infiltration and expression of matrix metalloproteinase. Furthermore, AS-IV abrogated Bap-/Ang II-induced NF-κB activation and oxidative stress. In vitro , AS-IV inhibition of macrophage activation and NF-κB was correlated with increased phosphorylation of phosphatidylinositol 3-kinase (PI3-K)/AKT. Together, our findings suggest that AS-IV has potential as an intervention in the formation of AAA. (1)The protective effect of Astragaloside IV (AS-IV) on abdominal aortic aneurysm (AAA) is associated with its suppressing effects on inflammation in the aortic wall.(2)AS-IV abrogated 3,4-benzopyrene (Bap)/angiotensin II (Ang II)-induced nuclear factor-κB (NF-κB) activation and oxidative stress.(3)AS-IV inhibited Bap-induced RAW264.7 macrophage cells activation by inhibiting oxidative stress and NF-κB activation through phosphatidylinositol 3-kinase (PI3-K)/AKT pathway.AS-IV is a potential preventive agent for cigarette smoking-related AAA.

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.

[Coronary circulation in asymmetrical hypertrophy of the interventricular septum. On a new pathogenic hypothesis].

PubMed

Sánchez, G; Orea, A; Trevethan, S; Martínez Ríos, M A

1984-01-01

Thirty-four patients with left ventricular hypertrophy were studied. In all cases the following parameters were analyzed: 1) Echocardiography:left ventricular diastolic and systolic diameters, ejection fraction, thickness and movement of interventricular septum and posterior wall of the left ventricle (LV) 2) Electrocardiography: R wave voltaje in precordial leads V2, V3 and V5 and electrical axis in frontal plane 3) Catheterization: intracavitary pressures in LV and aortic pressures 4) Left ventriculography: areas of altered contractility 5) Coronariography: distribution pattern of coronary arteries and number of first order branches of circumflex (CA) and anterior descending coronary arteries (ADCA). The population was divided into 2 groups. Group A (GA) was made up of 22 patients with concentric hypertrophy (CH) of the LV (15 with systemic hypertensive heart disease, 6 with aortic valvular stenosis and 1 idiopathic). Echocardiographic findings included posterior wall thickness (PWT) or septal thickness of 1.1. cm or more and interventricular septum-posterior wall thickness ratio (S/PW) of less than 1.3. Group B (GB) included 12 patients with asymmetric septal hypertrophy (ASH), idiopathic in 5, systemic hypertensive heart disease in 4 and aortic valvular stenosis in 3. In these patients the S/PW thickness ratio was greater than 1.3 and the thickness of either wall greater than 1.1. cm. When the data of the two groups were compared there were significant differences in relation to the presence of septal hypertrophy. The R wave voltage in V2, interventricular thickness and S/PW were greater in GB. In addition, septal movement was less in GB than in Group A (0.47 +/- 0.26 cm vs. 0.74 +/- 0.37 cm; P less than 0.05). PWT was also less in Group B than in A (B: 1.01 +/- 0.1 cm, A: 1.2 +/- 0.2 cm; P less than 0.001). The CA in Group B divided into fewer than 4 first order branches to the upper two thirds of the posterior and lateral walls of the LV in 91.6%. This distribution of circumflex branches was found in 31.8% of the patients in Group A (P less than 0.05). In Group B, the ADCA divided into septal branches with no more than 2 diagonal branches. The posterior descending artery dominated septal distribution in 100% of these cases (GA: 31.8%; P less than 0.05). The sum of the first order branches of the CA and the ADCA was 5.6 +/- 0.9 in Group A and 2.7 +/- 0.9 branches in Group B (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

k-t accelerated aortic 4D flow MRI in under two minutes: Feasibility and impact of resolution, k-space sampling patterns, and respiratory navigator gating on hemodynamic measurements.

PubMed

Bollache, Emilie; Barker, Alex J; Dolan, Ryan Scott; Carr, James C; van Ooij, Pim; Ahmadian, Rouzbeh; Powell, Alex; Collins, Jeremy D; Geiger, Julia; Markl, Michael

2018-01-01

To assess the performance of highly accelerated free-breathing aortic four-dimensional (4D) flow MRI acquired in under 2 minutes compared to conventional respiratory gated 4D flow. Eight k-t accelerated nongated 4D flow MRI (parallel MRI with extended and averaged generalized autocalibrating partially parallel acquisition kernels [PEAK GRAPPA], R = 5, TRes = 67.2 ms) using four k y -k z Cartesian sampling patterns (linear, center-out, out-center-out, random) and two spatial resolutions (SRes1 = 3.5 × 2.3 × 2.6 mm 3 , SRes2 = 4.5 × 2.3 × 2.6 mm 3 ) were compared in vitro (aortic coarctation flow phantom) and in 10 healthy volunteers, to conventional 4D flow (16 mm-navigator acceptance window; R = 2; TRes = 39.2 ms; SRes = 3.2 × 2.3 × 2.4 mm 3 ). The best k-t accelerated approach was further assessed in 10 patients with aortic disease. The k-t accelerated in vitro aortic peak flow (Qmax), net flow (Qnet), and peak velocity (Vmax) were lower than conventional 4D flow indices by ≤4.7%, ≤ 11%, and ≤22%, respectively. In vivo k-t accelerated acquisitions were significantly shorter but showed a trend to lower image quality compared to conventional 4D flow. Hemodynamic indices for linear and out-center-out k-space samplings were in agreement with conventional 4D flow (Qmax ≤ 13%, Qnet ≤ 13%, Vmax ≤ 17%, P > 0.05). Aortic 4D flow MRI in under 2 minutes is feasible with moderate underestimation of flow indices. Differences in k-space sampling patterns suggest an opportunity to mitigate image artifacts by an optimal trade-off between scan time, acceleration, and k-space sampling. Magn Reson Med 79:195-207, 2018. © 2018 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Comparing characteristics and clinical and echocardiographic outcomes in low-flow vs normal-flow severe aortic stenosis with preserved ejection fraction in an Asian population.

PubMed

Ngiam, Jinghao Nicholas; Tan, Benjamin Yong-Qiang; Sia, Ching-Hui; Lee, Glenn K M; Kong, William K F; Chan, Yiong-Huak; Poh, Kian-Keong

2017-05-01

In severe aortic stenosis (AS), deterioration of left ventricular ejection fraction (LVEF) to <50% is an AHA/ACC class I indication for valve replacement, regardless of symptoms. Controversy surrounds prognosis of low-flow AS compared to normal-flow, and no study has examined LVEF deterioration. We compared factors associated with LVEF deterioration (to <50%) and clinical outcomes. Consecutive subjects with low-flow (stroke volume index <35 mL/m 2 , n=56) and normal-flow (n=72) severe AS (aortic valve area <1 cm 2 ) with preserved LVEF (>50%) and with paired echocardiography were studied. Univariate and multivariate analyses identified factors associated with LVEF deterioration. Clinical outcomes were determined on follow-up for more than 5 years. Significant LVEF deterioration (to <50%) was seen in 18% of low-flow (initial LVEF 63±8% to 32±9%) and 18% of normal-flow AS (61±7% to 31±12%). Independent factors in low-flow AS were hypertension (OR: 30.7, 95% CI: 2.0-467.6, P=.014) and higher end-systolic wall stress (OR: 1.086, 95% CI: 1.022-1.153, P=.008), compared to normal-flow, which were hypertension (OR: 15.9, 95% CI: 3.1-81.9, P=.001), higher septal E/E' ratio (OR: 1.16, 95% CI: 1.01-1.35, P=.043), lower septal S' velocity (OR: 0.204, 95% CI: 0.061-0.682, P=.010), and higher end-systolic wall stress (OR: 1.051, 95% CI: 1.001-1.104, P=.047). Overall, a third of the cohort experienced MACE, regardless of flow (log-rank 0.048, P=.827). However, aortic valve replacement (AVR) rates were lower in low-flow AS (20% vs 43%, P=.005). Low-flow AS despite normal LVEF appears similar to normal-flow in terms of LVEF deterioration and clinical outcomes in our Asian population. AVR rate was lower even though low-flow may not reflect less severe disease. © 2017, Wiley Periodicals, Inc.

Understanding the fluid mechanics behind transverse wall shear stress.

PubMed

Mohamied, Yumnah; Sherwin, Spencer J; Weinberg, Peter D

2017-01-04

The patchy distribution of atherosclerosis within arteries is widely attributed to local variation in haemodynamic wall shear stress (WSS). A recently-introduced metric, the transverse wall shear stress (transWSS), which is the average over the cardiac cycle of WSS components perpendicular to the temporal mean WSS vector, correlates particularly well with the pattern of lesions around aortic branch ostia. Here we use numerical methods to investigate the nature of the arterial flows captured by transWSS and the sensitivity of transWSS to inflow waveform and aortic geometry. TransWSS developed chiefly in the acceleration, peak systolic and deceleration phases of the cardiac cycle; the reverse flow phase was too short, and WSS in diastole was too low, for these periods to have a significant influence. Most of the spatial variation in transWSS arose from variation in the angle by which instantaneous WSS vectors deviated from the mean WSS vector rather than from variation in the magnitude of the vectors. The pattern of transWSS was insensitive to inflow waveform; only unphysiologically high Womersley numbers produced substantial changes. However, transWSS was sensitive to changes in geometry. The curvature of the arch and proximal descending aorta were responsible for the principal features, the non-planar nature of the aorta produced asymmetries in the location and position of streaks of high transWSS, and taper determined the persistence of the streaks down the aorta. These results reflect the importance of the fluctuating strength of Dean vortices in generating transWSS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Variability of 4D flow parameters when subjected to changes in MRI acquisition parameters using a realistic thoracic aortic phantom.

PubMed

Montalba, Cristian; Urbina, Jesus; Sotelo, Julio; Andia, Marcelo E; Tejos, Cristian; Irarrazaval, Pablo; Hurtado, Daniel E; Valverde, Israel; Uribe, Sergio

2018-04-01

To assess the variability of peak flow, mean velocity, stroke volume, and wall shear stress measurements derived from 3D cine phase contrast (4D flow) sequences under different conditions of spatial and temporal resolutions. We performed controlled experiments using a thoracic aortic phantom. The phantom was connected to a pulsatile flow pump, which simulated nine physiological conditions. For each condition, 4D flow data were acquired with different spatial and temporal resolutions. The 2D cine phase contrast and 4D flow data with the highest available spatio-temporal resolution were considered as a reference for comparison purposes. When comparing 4D flow acquisitions (spatial and temporal resolution of 2.0 × 2.0 × 2.0 mm 3 and 40 ms, respectively) with 2D phase-contrast flow acquisitions, the underestimation of peak flow, mean velocity, and stroke volume were 10.5, 10 and 5%, respectively. However, the calculated wall shear stress showed an underestimation larger than 70% for the former acquisition, with respect to 4D flow, with spatial and temporal resolution of 1.0 × 1.0 × 1.0 mm 3 and 20 ms, respectively. Peak flow, mean velocity, and stroke volume from 4D flow data are more sensitive to changes of temporal than spatial resolution, as opposed to wall shear stress, which is more sensitive to changes in spatial resolution. Magn Reson Med 79:1882-1892, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Contribution of collagen fiber undulation to regional biomechanical properties along porcine thoracic aorta.

PubMed

Zeinali-Davarani, Shahrokh; Wang, Yunjie; Chow, Ming-Jay; Turcotte, Raphaël; Zhang, Yanhang

2015-05-01

As major extracellular matrix components, elastin, and collagen play crucial roles in regulating the mechanical properties of the aortic wall and, thus, the normal cardiovascular function. The mechanical properties of aorta, known to vary with age and multitude of diseases as well as the proximity to the heart, have been attributed to the variations in the content and architecture of wall constituents. This study is focused on the role of layer-specific collagen undulation in the variation of mechanical properties along the porcine descending thoracic aorta. Planar biaxial tensile tests are performed to characterize the hyperelastic anisotropic mechanical behavior of tissues dissected from four locations along the thoracic aorta. Multiphoton microscopy is used to image the associated regional microstructure. Exponential-based and recruitment-based constitutive models are used to account for the observed mechanical behavior while considering the aortic wall as a composite of two layers with independent properties. An elevated stiffness is observed in distal regions compared to proximal regions of thoracic aorta, consistent with sharper and earlier collagen recruitment estimated for medial and adventitial layers in the models. Multiphoton images further support our prediction that higher stiffness in distal regions is associated with less undulation in collagen fibers. Recruitment-based models further reveal that regardless of the location, collagen in the media is recruited from the onset of stretching, whereas adventitial collagen starts to engage with a delay. A parameter sensitivity analysis is performed to discriminate between the models in terms of the confidence in the estimated model parameters.

Crosslinked elastic fibers are necessary for low energy loss in the ascending aorta.

PubMed

Kim, Jungsil; Staiculescu, Marius Catalin; Cocciolone, Austin J; Yanagisawa, Hiromi; Mecham, Robert P; Wagenseil, Jessica E

2017-08-16

In the large arteries, it is believed that elastin provides the resistance to stretch at low pressure, while collagen provides the resistance to stretch at high pressure. It is also thought that elastin is responsible for the low energy loss observed with cyclic loading. These tenets are supported through experiments that alter component amounts through protease digestion, vessel remodeling, normal growth, or in different artery types. Genetic engineering provides the opportunity to revisit these tenets through the loss of expression of specific wall components. We used newborn mice lacking elastin (Eln -/- ) or two key proteins (lysyl oxidase, Lox -/- , or fibulin-4, Fbln4 -/- ) that are necessary for the assembly of mechanically-functional elastic fibers to investigate the contributions of elastic fibers to large artery mechanics. We determined component content and organization and quantified the nonlinear and viscoelastic mechanical behavior of Eln -/- , Lox -/- , and Fbln4 -/- ascending aorta and their respective controls. We confirmed that the lack of elastin, fibulin-4, or lysyl oxidase leads to absent or highly fragmented elastic fibers in the aortic wall and a 56-97% decrease in crosslinked elastin amounts. We found that the resistance to stretch at low pressure is decreased only in Eln -/- aorta, confirming the role of elastin in the nonlinear mechanical behavior of the aortic wall. Dissipated energy with cyclic loading and unloading is increased 53-387% in Eln -/- , Lox -/- , and Fbln4 -/- aorta, indicating that not only elastin, but properly assembled and crosslinked elastic fibers, are necessary for low energy loss in the aorta. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prosthetic Valve Endocarditis Caused by Bartonella henselae: A Case Report of Molecular Diagnostics Informing Nonsurgical Management

PubMed Central

Bartley, Patricia; Angelakis, Emmanouil; Raoult, Didier; Sampath, Rangarajan; Bonomo, Robert A.

2016-01-01

Identifying the pathogen responsible for culture-negative valve endocarditis often depends on molecular studies performed on surgical specimens. A patient with Ehlers-Danlos syndrome who had an aortic graft, a mechanical aortic valve, and a mitral anulloplasty ring presented with culture-negative prosthetic valve endocarditis and aortic graft infection. Research-based polymerase chain reaction (PCR)/electrospray ionization mass spectrometry on peripheral blood samples identified Bartonella henselae. Quantitative PCR targeting the16S-23S ribonucleic acid intergenic region and Western immunoblotting confirmed this result. This, in turn, permitted early initiation of pathogen-directed therapy and subsequent successful medical management of B henselae prosthetic valve endocarditis and aortic graft infection. PMID:27844027

Efficacy of the Stonehenge Technique for Minimally Invasive Aortic Valve Replacement via Right Infraaxillary Thoracotomy

PubMed Central

Kin, Hajime; Kitamoto, Shohei; Yamanaka, Shota; Nishida, Hidefumi; Nishigawa, Kosaku; Takanashi, Shuichiro

2017-01-01

Minimally invasive cardiac surgeries for aortic valve replacement (AVR) are still a technical challenge for surgeons because these procedures are undertaken through small incisions and deep surgical fields. Although AVR via vertical infraaxillary thoracotomy can be a cosmetically superior option, a disadvantage of this approach is the distance between the thoracotomy incision and the ascending aorta. Therefore, we devised a technique to perform all manipulations using the fingertips without the aid of a knot pusher or long-shafted surgical instruments. This was achieved by particular placement of several retracted sutures to the right chest wall. We named placement of these sutures the “Stonehenge technique.” In conclusion, AVR via vertical infraaxillary thoracotomy with our Stonehenge technique can be safely and simply performed with superior cosmetic advantages. PMID:28123153

Elasticity/distensibility of the ascending aorta: basal conditions and simulated conditions from space flights.

PubMed

Alessandri, N; Tufano, F; Petrassi, M; Alessandri, C; Lanzi, L; Fusco, L; Moscariello, F; De Angelis, C; Tomao, E

2010-05-01

The hysto-morfological composition of the ascending aorta wall gives to the vessel its characteristic elasticity/distensibility, which is deteriorated due to both physiological (age) and pathological events (hypertension, diabetes, dyslipidemia). This contributes to reduce the wall elasticity and to occurrence of cardiovascular events. Thirty young healthy subjects (20 males, 10 females, age <30 yr), were subjected to different postural conditions with and without Lower Body Negative Pressure (LBNP) with conventional procedures, to simulate the microgravity conditions in space flight. During this procedure the cardiovascular parameters and the aorta elasticity were assessed with ecocardiography. The observation of results and statistical comparison showed that despite different hemodynamic conditions and with significant variation of blood pressure related to posture, elasticity/distensibility did not change significantly. The elasticity/distensibility of arterial vessels is the result of two interdependent variables such as blood pressure and systolic and diastolic diameters. While blood pressure and heart rate vary physiologically in relation to posture, the compensation of the vessel diameters modifications maintains the aortic compliance invariate. Therefore, in young healthy people, despite the significant postural and the sudden pressure changes (equivalent to parietal stress) aortic compliance does not alter. This behavior might be related to the low rate of cardiovascular events that are present in healthy people aged under 30 yrs.

Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice.

PubMed

Martel, Catherine; Li, Wenjun; Fulp, Brian; Platt, Andrew M; Gautier, Emmanuel L; Westerterp, Marit; Bittman, Robert; Tall, Alan R; Chen, Shu-Hsia; Thomas, Michael J; Kreisel, Daniel; Swartz, Melody A; Sorci-Thomas, Mary G; Randolph, Gwendalyn J

2013-04-01

Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic drainage from skin--1 surgical and the other genetic--to quantitatively track RCT following injection of [3H]-cholesterol-loaded macrophages upstream of blocked or absent lymphatic vessels. Macrophage RCT was markedly impaired in both models, even at sites with a leaky vasculature. Inhibited RCT was downstream of cholesterol efflux from macrophages, since macrophage efflux of a fluorescent cholesterol analog (BODIPY-cholesterol) was not altered by impaired lymphatic drainage. We next addressed whether RCT was mediated by lymphatic vessels from the aortic wall by loading the aortae of donor atherosclerotic Apoe-deficient mice with [2H]6-labeled cholesterol and surgically transplanting these aortae into recipient Apoe-deficient mice that were treated with anti-VEGFR3 antibody to block lymphatic regrowth or with control antibody to allow such regrowth. [2H]-Cholesterol was retained in aortae of anti-VEGFR3-treated mice. Thus, the lymphatic vessel route is critical for RCT from multiple tissues, including the aortic wall. These results suggest that supporting lymphatic transport function may facilitate cholesterol clearance in therapies aimed at reversing atherosclerosis.

Evaluation of the thrombus of abdominal aortic aneurysms using contrast enhanced ultrasound - preliminary results

NASA Astrophysics Data System (ADS)

Łukasiewicz, Adam; Garkowski, Adam; Rutka, Katarzyna; Janica, Jacek; Łebkowska, Urszula

2016-09-01

It is hypothesized that the degree of vascularization of the thrombus may have a significant impact on the rupture of aortic aneurysms. The presence of neovascularization of the vessel wall and mural thrombus has been confirmed only in histopathological studies. However, no non-invasive imaging technique of qualitative assessment of thrombus and neovascularization has been implemented so far. Contrast-enhanced ultrasound (CEUS) has been proposed as a feasible and minimally invasive technique for in vivo visualization of neovascularization in the evaluation of tumors and atherosclerotic plaques. The aim of this study was the evaluation of mural thrombus and AAAs wall with CEUS. CEUS was performed in a group of seventeen patients with AAAs. The mural thrombus enhancement was recognized in 12 cases, yet no significant correlation between the degree of contrast enhancement and AAAs diameter, thrombus width, and thrombus echogenicity was found. We observed a rise in AAAs thrombus heterogeneity with the increase in the aneurysm diameter (r = 0.62, p = 0.017). In conclusion CEUS can visualize small channels within AAAs thrombus, which could be a result of an ongoing angiogenesis. There is a need for further research to find out whether the degree of vascularization of the thrombus may have a significant impact on the rupture of aneurysms.

Modeling of the aorta artery aneurysms and renal artery stenosis using cardiovascular electronic system

PubMed Central

Hassani, Kamran; Navidbakhsh, Mahdi; Rostami, Mostafa

2007-01-01

Background The aortic aneurysm is a dilatation of the aortic wall which occurs in the saccular and fusiform types. The aortic aneurysms can rupture, if left untreated. The renal stenosis occurs when the flow of blood from the arteries leading to the kidneys is constricted by atherosclerotic plaque. This narrowing may lead to the renal failure. Previous works have shown that, modelling is a useful tool for understanding of cardiovascular system functioning and pathophysiology of the system. The present study is concerned with the modelling of aortic aneurysms and renal artery stenosis using the cardiovascular electronic system. Methods The geometrical models of the aortic aneurysms and renal artery stenosis, with different rates, were constructed based on the original anatomical data. The pressure drop of each section due to the aneurysms or stenosis was computed by means of computational fluid dynamics method. The compliance of each section with the aneurysms or stenosis is also calculated using the mathematical method. An electrical system representing the cardiovascular circulation was used to study the effects of these pressure drops and the compliance variations on this system. Results The results showed the decreasing of pressure along the aorta and renal arteries lengths, due to the aneurysms and stenosis, at the peak systole. The mathematical method demonstrated that compliances of the aorta sections and renal increased with the expansion rate of the aneurysms and stenosis. The results of the modelling, such as electrical pressure graphs, exhibited the features of the pathologies such as hypertension and were compared with the relevant experimental data. Conclusion We conclude from the study that the aortic aneurysms as well as renal artery stenosis may be the most important determinant of the arteries rupture and failure. Furthermore, these pathologies play important rules in increase of the cardiovascular pulse pressure which leads to the hypertension. PMID:17559685

Improving proximal fixation and seal with the HeliFx Aortic EndoAnchor.

PubMed

Deaton, David H

2012-12-01

Endovascular aneurysm repair (EVAR) transformed the therapy for aortic aneurysms and introduced an era of widespread use for endovascular procedures in a variety of vascular beds. Although dramatic improvements in acute outcomes drove the early enthusiasm for EVAR, a realization that the long-term integrity of the endoprostheses used for EVAR were sometimes inferior to the results obtained with open surgical reconstruction dampened enthusiasm for their use in low-risk and younger patients who mandated long-term follow-up. While early EVAR failure modes are often related to technical aspects of the implantation, late failures are often related to the implant migrating from its original longitudinal position or losing wall apposition in the face of continued aneurysmal dilatation. Migration, or the failure of longitudinal fixation, results in gradual loss of aortic approximation and the eventual repressurization of the aneurysm sac with its attendant risks of growth and rupture. The inability of stent- and barb-based endovascular fixation to resist aortic dilatation at the site of fixation also represents a late failure mode that can result in aneurysm rupture. A variety of endostaples or endoanchors designed to replicate the function of an interrupted aortic suture have been proposed and tested to varying degrees over the years. The device designed and produced by Aptus EndoSystems, now called the HeliFx Aortic EndoAnchor is the only independent endovascular fixation device that has achieved significant clinical usage and Food and Drug Administration approval. The experience with this device is now more than 5 years and it is approved for use in the broad market across both Europe and the United States. This article will review the engineering and design concepts underlying the HeliFx device as well as the in vitro and in vivo results using this device. Finally, a discussion of the potential for technical, procedural, and endograft innovation based on the availability of endovascular suturing will be reviewed. Copyright © 2012. Published by Elsevier Inc.

Low-carbohydrate diets reduce lipid accumulation and arterial inflammation in guinea pigs fed a high-cholesterol diet.

PubMed

Leite, Jose O; DeOgburn, Ryan; Ratliff, Joseph; Su, Randy; Smyth, Joan A; Volek, Jeff S; McGrane, Mary M; Dardik, Alan; Fernandez, Maria Luz

2010-04-01

Low-carbohydrate diets (LCD) efficiently induce weight loss and favorably affect plasma lipids, however, the effect of LCD on atherosclerosis is still argued. To evaluate the effect of LCD on the prevention of atherosclerosis. Twenty guinea pigs were fed either a LCD or a low-fat diet (LFD) in combination with high-cholesterol (0.25g/100g) for 12 weeks. The percentage energy of macronutrient distribution was 10:65:25 for carbohydrate:fat:protein for the LCD, and 55:20:25 for the LFD. Plasma lipids were measured using colorimetric assays. Plasma and aortic oxidized (oxLDL) were quantified using ELISA methods. Inflammatory cytokines were measured in aortic homogenates using an immunoassay. H&E stained sections of aortic sinus and Schultz stained sections of carotid arteries were examined. LDL cholesterol was lower in the LCD compared to the LFD group (71.9+/-34.8 vs. 81.7+/-26.9mg/dL; p=0.039). Aortic cholesterol was also lower in the LCD (4.98+/-1.3mg/g) compared to the LFD group (6.68+/-2.0mg/g); p<0.05. The Schultz staining method confirmed less aortic cholesterol accumulation in the LCD group. Plasma oxLDL did not differ between groups, however, aortic oxLDL was 61% lower in the LCD compared to the LFD group (p=0.045). There was a positive correlation (r=0.63, p=0.03) between oxLDL and cholesterol concentration in the aorta of LFD group, which was not observed in LCD group (r=-0.05, p=0.96). Inflammatory markers were reduced in guinea pigs from the LCD group (p<0.05) and they were correlated with the decreases in oxLDL in aorta. These results suggest that LCD not only decreases lipid deposition, but also prevents the accumulation of oxLDL and reduces inflammatory cytokines within the arterial wall and may prevent atherosclerosis. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Echocardiographic Assessment of Aortic Pulse-Wave Velocity: Validation against Invasive Pressure Measurements.

PubMed

Styczynski, Grzegorz; Rdzanek, Adam; Pietrasik, Arkadiusz; Kochman, Janusz; Huczek, Zenon; Sobieraj, Piotr; Gaciong, Zbigniew; Szmigielski, Cezary

2016-11-01

Aortic pulse-wave velocity (PWV) is a measure of aortic stiffness that has a prognostic role in various diseases and in the general population. A number of methods are used to measure PWV, including Doppler ultrasound. Although echocardiography has been used for PWV measurement, to the authors' knowledge, it has never been tested against an invasive reference method at the same time point. Therefore, the aim of this study was to compare prospectively an echocardiographic PWV measurement, called echo-PWV, with an invasive study. Forty-five patients (mean age, 66 years; 60% men) underwent simultaneous intra-arterial pressure recording and echocardiographic Doppler flow evaluation during elective cardiac catheterization. Proximal pressure and Doppler waveforms were acquired in the aortic arch. Distal pressure waveforms were registered in the right and distal Doppler waveforms in the left external iliac artery. Transit time was measured as a delay of the foot of pressure or Doppler waveform in the distal relative to the proximal location. Distance was measured on the catheter for invasive PWV and over the surface for echo-PWV. Echo-PWV was calculated as distance divided by transit time. In the whole group, mean invasive PWV was 9.38 m/sec and mean echo-PWV was 9.51 m/sec (P = .78). The Pearson' correlation coefficient between methods was 0.93 (P < .0001). A Bland-Altman plot revealed a mean difference between invasive PWV and echo-PWV of 0.13 ± 0.79 m/sec. Echo-PWV, based on Doppler echocardiography, is a reliable method of aortic PWV measurement, with a close correlation with invasive assessment. Wider implementation of the echo-PWV method for the evaluation of aortic wall stiffness can further expand the clinical and scientific utility of echocardiography. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Defining acute aortic syndrome after trauma: Are Abbreviated Injury Scale codes a useful surrogate descriptor?

PubMed

Leach, R; McNally, Donal; Bashir, Mohamad; Sastry, Priya; Cuerden, Richard; Richens, David; Field, Mark

2012-10-01

The severity and location of injuries resulting from vehicular collisions are normally recorded in Abbreviated Injury Scale (AIS) code; we propose a system to link AIS code to a description of acute aortic syndrome (AAS), thus allowing the hypothesis that aortic injury is progressive with collision kinematics to be tested. Standard AIS codes were matched with a clinical description of AAS. A total of 199 collisions that resulted in aortic injury were extracted from a national automotive collision database and the outcomes mapped onto AAS descriptions. The severity of aortic injury (AIS severity score) and stage of AAS progression were compared with collision kinematics and occupant demographics. Post hoc power analyses were used to estimate maximum effect size. The general demographic distribution of the sample represented that of the UK population in regard to sex and age. No significant relationship was observed between estimated test speed, collision direction, occupant location or seat belt use and clinical progression of aortic injury (once initiated). Power analysis confirmed that a suitable sample size was used to observe a medium effect in most of the cases. Similarly, no association was observed between injury severity and collision kinematics. There is sufficient information on AIS severity and location codes to map onto the clinical AAS spectrum. It was not possible, with this data set, to consider the influence of collision kinematics on aortic injury initiation. However, it was demonstrated that after initiation, further progression along the AAS pathway was not influenced by collision kinematics. This might be because the injury is not progressive, because the vehicle kinematics studied do not fully represent the kinematics of the occupants, or because an unknown factor, such as stage of cardiac cycle, dominates. Epidemiologic/prognostic study, level IV.

Effects of smoking on arterial distensibility, central aortic pressures and left ventricular mass.

PubMed

Markus, Marcello Ricardo Paulista; Stritzke, Jan; Baumeister, Sebastian Edgar; Siewert, Ulrike; Baulmann, Johannes; Hannemann, Anke; Schipf, Sabine; Meisinger, Christa; Dörr, Marcus; Felix, Stephan Burkhart; Keil, Ulrich; Völzke, Henry; Hense, Hans-Werner; Schunkert, Heribert

2013-10-03

The effects of smoking on central aortic pressures and the age-related increase in left ventricular mass (LVM) are largely unknown. We studied the relationship between smoking, arterial distensibility, central aortic pressures and left ventricular mass in two population-based studies. Data was obtained from two German population-based studies (KORA and SHIP, participants' ages 25-84 years). We identified 114 normotensive current smokers and 185 normotensive all-time non-smokers in KORA as well as 400 and 588 such individuals in SHIP. Echocardiographic LVM was obtained at baseline (T0) and follow-up after ten years (T1) in KORA and at follow-up (T1) in SHIP. Additionally, pulse-wave analysis-based central aortic pressure and augmentation index (AIx) were measured at T1 in KORA. Cross-sectional analysis, using KORA T0 and SHIP T1, revealed in both studies a higher covariate-adjusted LVM and left ventricular mass index (LVMI) in smokers as compared with non-smokers. Moreover, in the KORA T1 examination, the smokers demonstrated a more pronounced increase, relative to baseline, of LVM (+13.5%) and LVMI (+13.4%) compared to non-smokers (+8.59% and +8.65%; p=0.036 and 0.042, respectively). Additionally, at KORA T1 smokers had a higher central systolic blood pressure and higher AIx than non-smokers (p=0.012 and p=0.001, respectively). The difference in central aortic pressure due to enhanced and more prolonged wave reflection may explain our finding of a further pronounced increase in left ventricular wall thickness and mass over time in smokers. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Does altered aortic flow in marfan syndrome relate to aortic root dilatation?

PubMed

Wang, Hung-Hsuan; Chiu, Hsin-Hui; Tseng, Wen-Yih Isaac; Peng, Hsu-Hsia

2016-08-01

To examine possible hemodynamic alterations in adolescent to adult Marfan syndrome (MFS) patients with aortic root dilatation. Four-dimensional flow MRI was performed in 20 MFS patients and 12 age-matched normal subjects with a 3T system. The cross-sectional areas of 10 planes along the aorta were segmented for calculating the axial and circumferential wall shear stress (WSSaxial , WSScirc ), oscillatory shear index (OSIaxial , OSIcirc ), and the nonroundness (NR), presenting the asymmetry of segmental WSS. Pearson's correlation analysis was performed to present the correlations between the quantified indices and the body surface area (BSA), aortic root diameter (ARD), and Z score of the ARD. P < 0.05 indicated statistical significance. Patients exhibited lower WSSaxial in the aortic root and the WSScirc in the arch (P < 0.05-0.001). MFS patients exhibited higher OSIaxial and OSIcirc in the sinotubular junction and arch, but lower OSIcirc in the descending aorta (all P < 0.05). The NR values were lower in patients (P < 0.05). The WSSaxial or WSScirc exhibited moderate to strong correlations with BSA, ARD, or Z score (R(2)  = 0.50-0.72) in MFS patients. The significant differences in the quantified indices, which were associated with BSA, ARD, or Z score, in MFS were opposite to previous reports for younger MFS patients, indicating that altered flows in MFS patients may depend on the disease progress. The possible time dependency of hemodynamic alterations in MFS patients strongly suggests that longitudinal follow-up of 4D Flow is needed to comprehend disease progress. J. Magn. Reson. Imaging 2016;44:500-508. © 2016 Wiley Periodicals, Inc.

Elevated levels of protein-bound p-hydroxyphenylacetaldehyde, an amino-acid-derived aldehyde generated by myeloperoxidase, are present in human fatty streaks, intermediate lesions and advanced atherosclerotic lesions.

PubMed Central

Hazen, S L; Gaut, J P; Crowley, J R; Hsu, F F; Heinecke, J W

2000-01-01

Reactive aldehydes might have a pivotal role in the pathogenesis of atherosclerosis by covalently modifying low-density lipoprotein (LDL). However, the identities of the aldehyde adducts that form on LDL in vivo are not yet clearly established. We previously demonstrated that the haem protein myeloperoxidase oxidizes proteins in the human artery wall. We also have shown that p-hydroxyphenylacetaldehyde (pHA), the aldehyde that forms when myeloperoxidase oxidizes L-tyrosine, covalently modifies the N(epsilon)-lysine residues of proteins. The resulting Schiff base can be quantified as N(epsilon)-[2-(p-hydroxyphenyl)ethyl]lysine (pHA-lysine) after reduction with NaCNBH(3). Here we demonstrate that pHA-lysine is a marker for LDL that has been modified by myeloperoxidase, and that water-soluble, but not lipid-soluble, antioxidants inhibit the modification of LDL protein. To determine whether myeloperoxidase-generated aldehydes might modify LDL in vivo, we used a combination of isotope-dilution GC-MS to quantify pHA-lysine in aortic tissues at various stages of lesion evolution. We also analysed LDL isolated from atherosclerotic aortic tissue. Comparison of normal and atherosclerotic aortic tissue demonstrated a significant elevation (more than 10-fold) of the reduced Schiff base adduct in fatty streaks, intermediate lesions and advanced lesions compared with normal aortic tissue. Moreover, the level of pHA-lysine in LDL recovered from atherosclerotic aortic intima was 200-fold that in plasma LDL of healthy donors. These results indicate that pHA-lysine, a specific covalent modification of LDL, is generated in human atherosclerotic vascular tissue. They also raise the possibility that reactive aldehydes generated by myeloperoxidase have a role in converting LDL into an atherogenic lipoprotein. PMID:11104675

Regular Exercise Reduces Endothelial Cortical Stiffness in Western Diet-Fed Female Mice.

PubMed

Padilla, Jaume; Ramirez-Perez, Francisco I; Habibi, Javad; Bostick, Brian; Aroor, Annayya R; Hayden, Melvin R; Jia, Guanghong; Garro, Mona; DeMarco, Vincent G; Manrique, Camila; Booth, Frank W; Martinez-Lemus, Luis A; Sowers, James R

2016-11-01

We recently showed that Western diet-induced obesity and insulin resistance promotes endothelial cortical stiffness in young female mice. Herein, we tested the hypothesis that regular aerobic exercise would attenuate the development of endothelial and whole artery stiffness in female Western diet-fed mice. Four-week-old C57BL/6 mice were randomized into sedentary (ie, caged confined, n=6) or regular exercise (ie, access to running wheels, n=7) conditions for 16 weeks. Exercise training improved glucose tolerance in the absence of changes in body weight and body composition. Compared with sedentary mice, exercise-trained mice exhibited reduced endothelial cortical stiffness in aortic explants (sedentary 11.9±1.7 kPa versus exercise 5.5±1.0 kPa; P<0.05), as assessed by atomic force microscopy. This effect of exercise was not accompanied by changes in aortic pulse wave velocity (P>0.05), an in vivo measure of aortic stiffness. In comparison, exercise reduced femoral artery stiffness in isolated pressurized arteries and led to an increase in femoral internal artery diameter and wall cross-sectional area (P<0.05), indicative of outward hypertrophic remodeling. These effects of exercise were associated with an increase in femoral artery elastin content and increased number of fenestrae in the internal elastic lamina (P<0.05). Collectively, these data demonstrate for the first time that the aortic endothelium is highly plastic and, thus, amenable to reductions in stiffness with regular aerobic exercise in the absence of changes in in vivo whole aortic stiffness. Comparatively, the same level of exercise caused destiffening effects in peripheral muscular arteries, such as the femoral artery, that perfuse the working limbs. © 2016 American Heart Association, Inc.

Four Surgical Modifications to the Classic Elastase Perfusion Aneurysm Model Enable Haemodynamic Alterations and Extended Elastase Perfusion.

PubMed

Busch, Albert; Chernogubova, Ekaterina; Jin, Hong; Meurer, Felix; Eckstein, Hans-Henning; Kim, Mia; Maegdefessel, Lars

2018-04-24

Abdominal aortic aneurysm (AAA) is an individual and socioeconomic burden in today's ageing society. Treatment relies on surgical exclusion of the dilated aorta by open or endovascular repair. For research purposes, animal models are necessary and the elastase induced aneurysm model closely mimics end stage human aneurysm disease. To improve the translational value of this model, four modifications to the classic elastase perfusion procedure (PPE) in relation to human aneurysm morphology were conducted. In ten week old male C57BL/6J wild type mice the PPE procedure was modified in four ways using two different techniques. Flow alteration was simulated by partial ligation of the common iliac artery or the distal aorta. Additionally, careful exploration of the abdominal aortic branches allowed PPE induction at the suprarenal and iliac level. Molecular biology, ultrasound, and immunohistochemistry were used to evaluate these pilot results. Two aortic outflow obstructions simulating distal aortic or iliac stenosis significantly increase murine AAA diameter (p = .046), and affect local vascular wall remodelling. Suprarenal aortic dissection allows a juxtarenal aneurysm to be induced, similar to the angiotensin II induced aneurysm model. A separate investigation for canonical activation of transforming growth factor β in the two embryonically distinct juxtarenal and infrarenal segments showed no distinct difference. Creating an aortoiliac bifurcated aneurysm completes the mimicry of human aneurysm morphology. The alteration of the classic PPE aneurysm by outflow modulation and further elastase perfusion to the juxtarenal and aortoiliac segment modifies morphology and diameter, and thus increases the translational value in future research. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Systemic Upregulation of IL-10 (Interleukin-10) Using a Nonimmunogenic Vector Reduces Growth and Rate of Dissecting Abdominal Aortic Aneurysm.

PubMed

Adam, Matti; Kooreman, Nigel; Jagger, Ann; Wagenhaeuser, Markus U; Mehrkens, Dennis; Wang, Yongming; Kayama, Yosuke; Toyama, Kensuke; Raaz, Uwe; Schellinger, Isabel N; Maegdefessel, Lars; Spin, Joshua M; Hamming, Jaap F; Quax, Paul H A; Baldus, Stephan; Wu, Joseph C; Tsao, Philip S

2018-06-07

Recruitment of immunologic competent cells to the vessel wall is a crucial step in formation of abdominal aortic aneurysms (AAA). Innate immunity effectors (eg, macrophages), as well as mediators of adaptive immunity (eg, T cells), orchestrate a local vascular inflammatory response. IL-10 (interleukin-10) is an immune-regulatory cytokine with a crucial role in suppression of inflammatory processes. We hypothesized that an increase in systemic IL-10-levels would mitigate AAA progression. Using a single intravenous injection protocol, we transfected an IL-10 transcribing nonimmunogenic minicircle vector into the Ang II (angiotensin II)-ApoE -/- infusion mouse model of AAA. IL-10 minicircle transfection significantly reduced average aortic diameter measured via ultrasound at day 28 from 166.1±10.8% (control) to 131.0±5.8% (IL-10 transfected). Rates of dissecting AAA were reduced by IL-10 treatment, with an increase in freedom from dissecting AAA from 21.5% to 62.3%. Using flow cytometry of aortic tissue from minicircle IL-10-treated animals, we found a significantly higher percentage of CD4 + /CD25 + /Foxp3 (forkhead box P3) + regulatory T cells, with fewer CD8 + /Granzyme B + cytotoxic T cells. Furthermore, isolated aortic macrophages produced less TNF-α (tumor necrosis factor-α), more IL-10, and were more likely to be MRC1 (mannose receptor, C type 1)-positive alternatively activated macrophages. These results concurred with gene expression analysis of LPS-stimulated and Ang II-primed human peripheral blood mononuclear cells. Taken together, we provide an effective gene therapy approach to AAA in mice by enhancing antiinflammatory and dampening proinflammatory pathways through minicircle-induced augmentation of systemic IL-10 expression. © 2018 American Heart Association, Inc.

Does altered aortic flow in marfan syndrome relate to aortic root dilatation?

PubMed Central

Wang, Hung‐Hsuan; Chiu, Hsin‐Hui; Tseng, Wen‐Yih Isaac

2016-01-01

Purpose To examine possible hemodynamic alterations in adolescent to adult Marfan syndrome (MFS) patients with aortic root dilatation. Materials and Methods Four‐dimensional flow MRI was performed in 20 MFS patients and 12 age‐matched normal subjects with a 3T system. The cross‐sectional areas of 10 planes along the aorta were segmented for calculating the axial and circumferential wall shear stress (WSSaxial, WSScirc), oscillatory shear index (OSIaxial, OSIcirc), and the nonroundness (NR), presenting the asymmetry of segmental WSS. Pearson's correlation analysis was performed to present the correlations between the quantified indices and the body surface area (BSA), aortic root diameter (ARD), and Z score of the ARD. P < 0.05 indicated statistical significance. Results Patients exhibited lower WSSaxial in the aortic root and the WSScirc in the arch (P < 0.05–0.001). MFS patients exhibited higher OSIaxial and OSIcirc in the sinotubular junction and arch, but lower OSIcirc in the descending aorta (all P < 0.05). The NR values were lower in patients (P < 0.05). The WSSaxial or WSScirc exhibited moderate to strong correlations with BSA, ARD, or Z score (R2 = 0.50–0.72) in MFS patients. Conclusion The significant differences in the quantified indices, which were associated with BSA, ARD, or Z score, in MFS were opposite to previous reports for younger MFS patients, indicating that altered flows in MFS patients may depend on the disease progress. The possible time dependency of hemodynamic alterations in MFS patients strongly suggests that longitudinal follow‐up of 4D Flow is needed to comprehend disease progress. J. Magn. Reson. Imaging 2016;44:500–508. PMID:26854646

Regression of left ventricular hypertrophy and aortic remodelling in NO-deficient hypertensive rats: effect of L-arginine and spironolactone.

PubMed

Paulis, L; Matuskova, J; Adamcova, M; Pelouch, V; Simko, J; Krajcirovicova, K; Potacova, A; Hulin, I; Janega, P; Pechanova, O; Simko, F

2008-09-01

We investigated, whether the substrate for nitric oxide (NO) formation -L-arginine - and the aldosterone receptor antagonist - spironolactone - are able to reverse alterations of the left ventricle (LV) and aorta in N(omega)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Six groups of male adult Wistar rats were investigated: controls after 4 and 7 weeks of experiment, rats treated with L-NAME for 4 weeks and three recovery groups: spontaneous-reversion (4 weeks L-NAME + 3 weeks placebo), spironolactone-induced reversion (4 weeks L-NAME + 3 weeks spironolactone) and L-arginine-induced reversion (4 weeks L-NAME+ 3 weeks L-arginine). Blood pressure was measured by tail-cuff plethysmography. Relative weight of the LV, myocardial fibrosis (based upon histomorphometry and hydroxyproline determination) and conjugated dienes in the LV and aortic cross-sectional area, inner diameter and wall thickness were determined. NO-synthase activity was investigated in the LV and aorta. L-NAME administration induced hypertension, left ventricular hypertrophy (LVH), LV fibrosis, aortic thickening and diminution of NO-synthase activity in the LV and aorta. Reduction in blood pressure and regression of LVH were observed in all recovery groups, yet reduction in LV fibrosis and aortic thickening were not. NO-synthase activity was restored only in the L-arginine and spironolactone group. In our study, the reversion of hypertension and LVH was not dependent on the restoration of NO-synthase activity. Moreover, LV fibrosis and aortic remodelling seem to be more resistant to conditions resulting in regression of LVH. Preserved level of fibrosis in the initial period of LVH regression might result in loss of structural homogeneity and possible functional alterations of the LV.

Blood flow characteristics in the aortic arch

NASA Astrophysics Data System (ADS)

Prahl Wittberg, Lisa; van Wyk, Stevin; Mihaiescu, Mihai; Fuchs, Laszlo; Gutmark, Ephraim; Backeljauw, Philippe; Gutmark-Little, Iris

2012-11-01

The purpose with this study is to investigate the flow characteristics of blood in the aortic arch. Cardiovascular diseases are associated with specific locations in the arterial tree. Considering atherogenesis, it is claimed that the Wall Shear Stress (WSS) along with its temporal and spatial gradients play an important role in the development of the disease. The WSS is determined by the local flow characteristics, that in turn depends on the geometry as well as the rheological properties of blood. In this numerical work, the time dependent fluid flow during the entire cardiac cycle is fully resolved. The Quemada model is applied to account for the non-Newtonian properties of blood, an empirical model valid for different Red Blood Cell loading. Data obtained through Cardiac Magnetic Resonance Imaging have been used in order to reconstruct geometries of the the aortic arch. Here, three different geometries are studied out of which two display malformations that can be found in patients having the genetic disorder Turner's syndrome. The simulations show a highly complex flow with regions of secondary flow that is enhanced for the diseased aortas. The financial support from the Swedish Research Council (VR) and the Sweden-America Foundation is gratefully acknowledged.

Gorham disease of the lumbar spine with an abdominal aortic aneurysm: a case report.

PubMed

Kakuta, Yohei; Iizuka, Haku; Kobayashi, Ryoichi; Iizuka, Yoichi; Takahashi, Toru; Mohara, Jun; Takagishi, Kenji

2014-01-01

Reports of Gorham disease of the lumbar spine complicated by abdominal aortic aneurysms are rare. We herein report the case of a patient with Gorham disease of the lumber spine involving an abdominal aortic aneurysm (AAA). Case report. A 49-year-old man had a 1-month history of right leg pain and severe low back pain. Plain lumbar radiography revealed an osteolytic lesion in the L4 vertebral body. Computed tomography images demonstrated the presence of an extensive osteolytic lesion in the L4 vertebral body and an AAA in front of the L4 vertebral body. The patient underwent mass resection, spinal reconstruction, and blood vessel prosthesis implantation. During surgery, it was found that the wall of the aorta had completely disappeared and was shielded by the tumor mass; therefore, we speculated that the mass in the lumbar spine had directly invaded the aorta. The patient was able to walk without right leg or low back pain 1 year after undergoing surgery. No recurrence was demonstrated in the magnetic resonance images taken 1 year and 10 months after surgery. Copyright © 2014 Elsevier Inc. All rights reserved.

Determination of oxidation state of iron in normal and pathologically altered human aortic valves

NASA Astrophysics Data System (ADS)

Czapla-Masztafiak, J.; Lis, G. J.; Gajda, M.; Jasek, E.; Czubek, U.; Bolechała, F.; Borca, C.; Kwiatek, W. M.

2015-12-01

In order to investigate changes in chemical state of iron in normal and pathologically altered human aortic valves X-ray absorption spectroscopy was applied. Since Fe is suspected to play detrimental role in aortic valve stenosis pathogenesis the oxidation state of this element has been determined. The experimental material consisted of 10 μm sections of valves excised during routine surgery and from autopsies. The experiment was performed at the MicroXAS beamline of the SLS synchrotron facility in Villigen (Switzerland). The Fe K-edge XANES spectra obtained from tissue samples were carefully analyzed and compared with the spectra of reference compounds containing iron in various chemical structures. The analysis of absorption edge position and shape of the spectra revealed that both chemical forms of iron are presented in valve tissue but Fe3+ is the predominant form. Small shift of the absorption edge toward higher energy in the spectra from stenotic valve samples indicates higher content of the Fe3+ form in pathological tissue. Such a phenomenon suggests the role of Fenton reaction and reactive oxygen species in the etiology of aortic valve stenosis. The comparison of pre-edge regions of XANES spectra for control and stenotic valve tissue confirmed no differences in local symmetry or spin state of iron in analyzed samples.

Gender, smoking, body size, and aneurysm geometry influence the biomechanical rupture risk of abdominal aortic aneurysms as estimated by finite element analysis.

PubMed

Lindquist Liljeqvist, Moritz; Hultgren, Rebecka; Siika, Antti; Gasser, T Christian; Roy, Joy

2017-04-01

Finite element analysis (FEA) has been suggested to be superior to maximal diameter measurements in predicting rupture of abdominal aortic aneurysms (AAAs). Our objective was to investigate to what extent previously described rupture risk factors were associated with FEA-estimated rupture risk. One hundred forty-six patients with an asymptomatic AAA of a 40- to 60-mm diameter were retrospectively identified and consecutively included. The patients' computed tomography angiograms were analyzed by FEA without (neutral) and with (specific) input of patient-specific mean arterial pressure (MAP), gender, family history, and age. The maximal wall stress/wall strength ratio was described as a rupture risk equivalent diameter (RRED), which translated this ratio into an average aneurysm diameter of corresponding rupture risk. In multivariate linear regression, RRED neutral increased with female gender (3.7 mm; 95% confidence interval [CI], 0.13-7.3) and correlated with patient height (0.27 mm/cm; 95% CI, 0.11-0.43) and body surface area (BSA, 16 mm/m 2 ; 95% CI, 8.3-24) and inversely with body mass index (BMI, -0.40 mm/kg m -2 ; 95% CI, -0.75 to -0.054) in a wall stress-dependent manner. Wall stress-adjusted RRED neutral was raised if the patient was currently smoking (1.1 mm; 95% CI, 0.21-1.9). Age, MAP, family history, and patient weight were unrelated to RRED neutral . In specific FEA, RRED specific increased with female gender, MAP, family history positive for AAA, height, and BSA, whereas it was inversely related to BMI. All results were independent of aneurysm diameter. Peak wall stress and RRED correlated with aneurysm diameter and lumen volume. Female gender, current smoking, increased patient height and BSA, and low BMI were found to increase the mechanical rupture risk of AAAs. Previously described rupture risk factors may in part be explained by patient characteristic-dependent variations in aneurysm biomechanics. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Using In Vivo and Tissue and Cell Explant Approaches to Study the Morphogenesis and Pathogenesis of the Embryonic and Perinatal Aorta.

PubMed

Misra, Ashish; Feng, Zhonghui; Zhang, Jiasheng; Lou, Zhi-Yin; Greif, Daniel M

2017-09-12

The aorta is the largest artery in the body. The aortic wall is composed of an inner layer of endothelial cells, a middle layer of alternating elastic lamellae and smooth muscle cells (SMCs), and an outer layer of fibroblasts and extracellular matrix. In contrast to the widespread study of pathological models (e.g., atherosclerosis) in the adult aorta, much less is known about the embryonic and perinatal aorta. Here, we focus on SMCs and provide protocols for the analysis of the morphogenesis and pathogenesis of embryonic and perinatal aortic SMCs in normal development and disease. Specifically, the four protocols included are: i) in vivo embryonic fate mapping and clonal analysis; ii) explant embryonic aorta culture; iii) SMC isolation from the perinatal aorta; and iv) subcutaneous osmotic mini-pump placement in pregnant (or non-pregnant) mice. Thus, these approaches facilitate the investigation of the origin(s), fate, and clonal architecture of SMCs in the aorta in vivo. They allow for modulating embryonic aorta morphogenesis in utero by continuous exposure to pharmacological agents. In addition, isolated aortic tissue explants or aortic SMCs can be used to gain insights into the role of specific gene targets during fundamental processes such as muscularization, proliferation, and migration. These hypothesis-generating experiments on isolated SMCs and the explanted aorta can then be assessed in the in vivo context through pharmacological and genetic approaches.

Modelling and numerical simulation of the in vivo mechanical response of the ascending aortic aneurysm in Marfan syndrome.

PubMed

García-Herrera, Claudio M; Celentano, Diego J; Herrera, Emilio A

2017-03-01

Marfan syndrome (MFS) is a genetic disorder that affects connective tissue, impairing cardiovascular structures and function, such as heart valves and aorta. Thus, patients with Marfan disease have a higher risk of developing circulatory problems associated with mitral and aortic valves prolapse, manifested as dilated aorta and aortic aneurysm. However, little is known about the biomechanical characteristics of these structures affected with MFS. This study presents the modelling and simulation of the mechanical response of human ascending aortic aneurysms in MFS under in vivo conditions with intraluminal pressures within normotensive and hypertensive ranges. We obtained ascending aortic segments from five adults with MFS subjected to a vascular prosthesis implantation replacing an aortic aneurysm. We characterised the arterial samples via ex vivo tensile test measurements that enable fitting the material parameters of a hyperelastic isotropic constitutive model. Then, these material parameters were used in a numerical simulation of an ascending aortic aneurysm subjected to in vivo normotensive and hypertensive conditions. In addition, we assessed different constraints related to the movement of the aortic root. Overall, our results provide not only a realistic description of the mechanical behaviour of the vessel, but also useful data about stress/stretch-based criteria to predict vascular rupture. This knowledge may be included in the clinical assessment to determine risk and indicate surgical intervention.

Ascending Aortic Dimensions in Former National Football League Athletes.

PubMed

Gentry, James L; Carruthers, David; Joshi, Parag H; Maroules, Christopher D; Ayers, Colby R; de Lemos, James A; Aagaard, Philip; Hachamovitch, Rory; Desai, Milind Y; Roselli, Eric E; Dunn, Reginald E; Alexander, Kezia; Lincoln, Andrew E; Tucker, Andrew M; Phelan, Dermot M

2017-11-01

Ascending aortic dimensions are slightly larger in young competitive athletes compared with sedentary controls, but rarely >40 mm. Whether this finding translates to aortic enlargement in older, former athletes is unknown. This cross-sectional study involved a sample of 206 former National Football League (NFL) athletes compared with 759 male subjects from the DHS-2 (Dallas Heart Study-2; mean age of 57.1 and 53.6 years, respectively, P <0.0001; body surface area of 2.4 and 2.1 m 2 , respectively, P <0.0001). Midascending aortic dimensions were obtained from computed tomographic scans performed as part of a NFL screening protocol or as part of the DHS. Compared with a population-based control group, former NFL athletes had significantly larger ascending aortic diameters (38±5 versus 34±4 mm; P <0.0001). A significantly higher proportion of former NFL athletes had an aorta of >40 mm (29.6% versus 8.6%; P <0.0001). After adjusting for age, race, body surface area, systolic blood pressure, history of hypertension, current smoking, diabetes mellitus, and lipid profile, the former NFL athletes still had significantly larger ascending aortas ( P <0.0001). Former NFL athletes were twice as likely to have an aorta >40 mm after adjusting for the same parameters. Ascending aortic dimensions were significantly larger in a sample of former NFL athletes after adjusting for their size, age, race, and cardiac risk factors. Whether this translates to an increased risk is unknown and requires further evaluation. © 2017 American Heart Association, Inc.

Coronary ostium occlusion by coronary cusp displacement in Williams syndrome.

PubMed

Shiohama, Tadashi; Fujii, Katsunori; Ebata, Ryota; Funabashi, Nobusada; Matsumiya, Goro; Saito, Yuko Kazato; Takechi, Fumie; Yonemori, Yoko; Nakatani, Yukio; Shimojo, Naoki

2016-06-01

Williams syndrome is a contiguous gene deletion syndrome resulting from a heterozygous deletion on chromosome 7q11.23, and is characterized by distinctive facial features and supravalvular aortic stenosis (SVAS). This syndrome rarely presents unpredictable cardiac death, and yet, as illustrated in the present case, it is still not possible to predict it, even on close monitoring. We herein describe the case of a 6-year-old Japanese girl with Williams syndrome, who had sudden cardiac collapse due to cardiac infarction after pharyngitis. Cardiac failure followed a critical course that did not respond to catecholamine support or heart rest with extracardiac mechanical support. Although marked coronary stenosis was not present, the left coronary cusp abnormally adhered to the aortic wall, which may synergistically cause coronary ostium occlusion with SVAS. Altered hemodynamic state, even that caused by the common cold, may lead to critical myocardial events in Williams syndrome with SVAS. © 2015 Japan Pediatric Society.

Early Enlargement of Aneurysmal Sac and Separation of EndoBags of Nellix Endovascular Aneurysm Sealing System as Signs of Increased Risk of Later Aneurysm Rupture.

PubMed

Cheng, Lik Fai; Cheung, Kwok Fai; Chan, Kwong Man; Ma, Johnny Ka Fai; Luk, Wing Hang; Chan, Micah Chi King; Ng, Carol Wing Kei; Mahboobani, Neeraj Ramesh; Ng, Wai Kin; Wong, Ting

2016-11-01

Nellix Endovascular Aneurysm Sealing (EVAS) system is a new concept and technology of abdominal aortic aneurysm (AAA) repair. Elective EVAS using Nellix device was performed for a 83-year-old man with AAA. 2-month post-EVAS CTA surveillance demonstrated mild enlargement of aneurysmal sac and separation of the EndoBags, but without detectable endoleak. The patient developed sudden AAA rupture with retroperitoneal hematoma at about 4 months after EVAS. We postulated that early enlargement of aneurysmal sac and separation of EndoBags of Nellix devices after EVAS, even without detectable endoleak, might indicate significant aneurysmal wall weakening with increased risk of later AAA rupture. To the best of the authors' knowledge, this was the first reported case of aortic rupture after EVAS without detectable endoleak during and after the procedure.

Echocardiographic features of impaired left ventricular diastolic function in Chagas's heart disease.

PubMed Central

Combellas, I; Puigbo, J J; Acquatella, H; Tortoledo, F; Gomez, J R

1985-01-01

To study left ventricular diastolic function in Chagas's disease, simultaneous echocardiograms, phonocardiograms, and apexcardiograms were recorded in 20 asymptomatic patients with positive Chagas's serology and no signs of heart disease (group 1), 12 with Chagas's heart disease and symptoms of ventricular arrhythmia but no heart failure (group 2), 20 normal subjects (group 3), and 12 patients with left ventricular hypertrophy (group 4). The recordings were digitised to determine left ventricular isovolumic relaxation time and the rate and duration of left ventricular cavity dimension increase and wall thinning. In groups 1 and 2 (a) aortic valve closure (A2) and mitral valve opening were significantly delayed relative to minimum dimension and were associated with prolonged isovolumic relaxation, (b) left ventricular cavity size was abnormally increased during isovolumic relaxation and abnormally reduced during isovolumic contraction, and (c) peak rate of posterior wall thinning and dimension increase were significantly reduced and duration of posterior wall thinning was significantly prolonged; both of these abnormalities occurred at the onset of diastolic filling. These abnormalities were more pronounced in group 2 and were accompanied by an increase in the height of the apexcardiogram "a" wave, an indication of pronounced atrial systole secondary to end diastolic filling impairment due to reduced left ventricular distensibility. Group 4, which had an established pattern of diastolic abnormalities, showed changes similar to those in group 2; however, the delay in aortic valve closure (A2) and in mitral valve opening and the degree of dimension change were greater in the latter group. Thus early isovolumic relaxation and left ventricular abnormalities were pronounced in the patients with Chagas's heart disease and may precede systolic compromise, which may become apparent in later stages of the disease. The digitised method is valuable in the early detection of myocardial damage. Images PMID:3155954

Effect of aorto-iliac bifurcation and iliac stenosis on flow dynamics in an abdominal aortic aneurysm

NASA Astrophysics Data System (ADS)

Patel, Shivam; Usmani, Abdullah Y.; Muralidhar, K.

2017-06-01

Physiological flows in rigid diseased arterial flow phantoms emulating an abdominal aortic aneurysm (AAA) under rest conditions with aorto-iliac bifurcation and iliac stenosis are examined in vitro through 2D PIV measurements. Flow characteristics are first established in the model resembling a symmetric AAA with a straight outlet tube. The influence of aorto-iliac bifurcation and iliac stenosis on AAA flow dynamics is then explored through a comparison of the nature of flow patterns, vorticity evolution, vortex core trajectory and hemodynamic factors against the reference configuration. Specifically, wall shear stress and oscillatory shear index in the bulge portion of the models are of interest. The results of this investigation indicate overall phenomenological similarity in AAA flow patterns across the models. The pattern is characterized by a central jet and wall-bounded vortices whose strength increases during the deceleration phase as it moves forward. The central jet impacts the wall of AAA at its distal end. In the presence of an aorto-iliac bifurcation as well as iliac stenosis, the flow patterns show diminished strength, expanse and speed of propagation of the primary vortices. The positions of the instantaneous vortex cores, determined using the Q-function, correlate with flow separation in the bulge, flow resistance due to a bifurcation, and the break in symmetry introduced by a stenosis in one of the legs of the model. Time-averaged WSS in a healthy aorta is around 0.70 N m-2 and is lowered to the range ±0.2 N m-2 in the presence of the downstream bifurcation with a stenosed common iliac artery. The consequence of changes in the flow pattern within the aneurysm on disease progression is discussed.

Role of endothelial permeability hotspots and endothelial mitosis in determining age-related patterns of macromolecule uptake by the rabbit aortic wall near branch points.

PubMed

Chooi, K Yean; Comerford, Andrew; Cremers, Stephanie J; Weinberg, Peter D

2016-07-01

Transport of macromolecules between plasma and the arterial wall plays a key role in atherogenesis. Scattered hotspots of elevated endothelial permeability to macromolecules occur in the aorta; a fraction of them are associated with dividing cells. Hotspots occur particularly frequently downstream of branch points, where lesions develop in young rabbits and children. However, the pattern of lesions varies with age, and can be explained by similar variation in the pattern of macromolecule uptake. We investigated whether patterns of hotspots and mitosis also change with age. Evans' Blue dye-labeled albumin was injected intravenously into immature or mature rabbits and its subsequent distribution in the aortic wall around intercostal branch ostia examined by confocal microscopy and automated image analysis. Mitosis was detected by immunofluorescence after adding 5-bromo-2-deoxiuridine to drinking water. Hotspots were most frequent downstream of branches in immature rabbits, but a novel distribution was observed in mature rabbits. Neither pattern was explained by mitosis. Hotspot uptake correlated spatially with the much greater non-hotspot uptake (p < 0.05), and the same pattern was seen when only the largest hotspots were considered. The pattern of hotspots changes with age. The data are consistent with there being a continuum of local permeabilities rather than two distinct mechanisms. The distribution of the dye, which binds to elastin and collagen, was similar to that of non-binding tracers and to lesions apart from a paucity at the lateral margins of branches that can be explained by lower levels of fibrous proteins in those regions. Copyright © 2016. Published by Elsevier Ireland Ltd.

A combined numerical and experimental framework for determining permeability properties of the arterial media.

PubMed

Comerford, A; Chooi, K Y; Nowak, M; Weinberg, P D; Sherwin, S J

2015-04-01

The medial layer of the arterial wall may play an important role in the regulation of water and solute transport across the wall. In particular, a high medial resistance to transport could cause accumulation of lipid-carrying molecules in the inner wall. In this study, the water transport properties of medial tissue were characterised in a numerical model, utilising experimentally obtained data for the medial microstructure and the relative permeability of different constituents. For the model, a new solver for flow in porous materials, based on a high-order splitting scheme, was implemented in the spectral/hp element library nektar++ and validated. The data were obtained by immersing excised aortic bifurcations in a solution of fluorescent protein tracer and subsequently imaging them with a confocal microscope. Cuboidal regions of interest were selected in which the microstructure and relative permeability of different structures were transformed to a computational mesh. Impermeable objects were treated fictitiously in the numerical scheme. On this cube, a pressure drop was applied in the three coordinate directions and the principal components of the permeability tensor were determined. The reconstructed images demonstrated the arrangement of elastic lamellae and interspersed smooth muscle cells in rat aortic media; the distribution and alignment of the smooth muscle cells varied spatially within the extracellular matrix. The numerical simulations highlighted that the heterogeneity of the medial structure is important in determining local water transport properties of the tissue, resulting in regional and directional variation of the permeability tensor. A major factor in this variation is the alignment and density of smooth muscle cells in the media, particularly adjacent to the adventitial layer.

COMPUTATIONAL SIMULATIONS DEMONSTRATE ALTERED WALL SHEAR STRESS IN AORTIC COARCTATION PATIENTS TREATED BY RESECTION WITH END-TO-END ANASTOMOSIS

PubMed Central

LaDisa, John F.; Dholakia, Ronak J.; Figueroa, C. Alberto; Vignon-Clementel, Irene E.; Chan, Frandics P.; Samyn, Margaret M.; Cava, Joseph R.; Taylor, Charles A.; Feinstein, Jeffrey A.

2011-01-01

Background Atherosclerotic plaque in the descending thoracic aorta (dAo) is related to altered wall shear stress (WSS) for normal patients. Resection with end-to-end anastomosis (RWEA) is the gold standard for coarctation of the aorta (CoA) repair, but may lead to altered WSS indices that contribute to morbidity. Methods Computational fluid dynamics (CFD) models were created from imaging and blood pressure data for control subjects and age- and gender-matched CoA patients treated by RWEA (4 male, 2 female, 15±8 years). CFD analysis incorporated downstream vascular resistance and compliance to generate blood flow velocity, time-averaged WSS (TAWSS) and oscillatory shear index (OSI) results. These indices were quantified longitudinally and circumferentially in the dAo, and several visualization methods were used to highlight regions of potential hemodynamic susceptibility. Results The total dAo area exposed to subnormal TAWSS and OSI was similar between groups, but several statistically significant local differences were revealed. Control subjects experienced left-handed rotating patterns of TAWSS and OSI down the dAo. TAWSS was elevated in CoA patients near the site of residual narrowings and OSI was elevated distally, particularly along the left dAo wall. Differences in WSS indices between groups were negligible more than 5 dAo diameters distal to the aortic arch. Conclusions Localized differences in WSS indices within the dAo of CoA patients treated by RWEA suggest that plaque may form in unique locations influenced by the surgical repair. These regions can be visualized in familiar and intuitive ways allowing clinicians to track their contribution to morbidity in longitudinal studies. PMID:21801315

Surgical infrarenal "neo-neck" technique during elective conversion after EVAR with suprarenal fixation.

PubMed

Bonvini, S; Wassermann, V; Menegolo, M; Scrivere, P; Grego, F; Piazza, M

2015-08-01

Conversion of a previous endovascular aneurysm repair (EVAR) with suprarenal fixation is a challenging situation even in the elective setting. The outcomes of a technique based on preservation of the first proximal covered stent of the endograft, used as a "neo-neck" for proximal anastomosis, are presented. From 2001 to 2014, nine patients underwent elective conversion of a previous suprarenally fixed EVAR. After supraceliac clamping, the aneurysm sac was opened and the endograft identified; the fabric was cut beyond the first covered stent together with its native aortic wall in order to create a "neo-neck." An aortic balloon was inflated into the visceral aorta to avoid back bleeding. A Dacron bifurcated tube graft (Intergard, Maquet) was then sutured to the neo-neck mimicking endobanding, passing the stitches into the aortic wall and the first covered stent. The mean age was 68 years (range, 52-84 years). The stent grafts removed were four Zenith (Cook Medical), three Endurant (Medtronic), and two E-vita (Jotec). The indication for conversion was type 1A (n = 2), type 2 (n = 2), and type 3 (n = 1) endoleak, complete endograft thrombosis (n = 2), and abdominal pain with sac enlargement with no radiological sign of endoleak (n = 2). Blood loss was 1,428 mL (range 500-3,000 mL); the visceral ischemic time to perform the proximal anastomosis was 23.5 min ± 2.3 min). The post-operative complication rate was 11% (n = 1/9) related to a case of sac wall bleeding requiring re-intervention; mortality at 30 days was 0%. At 22 months (range, 8-41) the computed tomography angiogram demonstrated no signs of leaks or anastomotic pseudoaneurysm. Preservation of the proximal covered stent of an endograft with suprarenal fixation used as an infrarenal "neo-neck" with incorporation of the aorta to the suture line during elective surgical explantation simplifies the procedure, and can be achieved with very low early morbidity and mortality; furthermore, it seems to be durable over mid-term follow up. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Heterogeneous histomorphology, yet homogeneous vascular smooth muscle cell dedifferentiation, characterize human aneurysm disease.

PubMed

Busch, Albert; Hartmann, Elena; Grimm, Caroline; Ergün, Süleyman; Kickuth, Ralph; Otto, Christoph; Kellersmann, Richard; Lorenz, Udo

2017-11-01

Abdominal aortic aneurysm (AAA) is a frequent, potentially life-threatening, disease that can only be treated by surgical means such as open surgery or endovascular repair. No alternative treatment is currently available, and despite expanding knowledge about the pathomechanism, clinical trials on medical aneurysm abrogation have led to inconclusive results. The heterogeneity of human AAA based on histologic examination is thereby generally neglected. In this study we aimed to further elucidate the role of these differences in aneurysm disease. Tissue samples from AAA and popliteal artery aneurysm patients were examined by histomorphologic analysis, immunohistochemistry, Western blot, and polymerase chain reaction. The results were correlated with clinical data such as aneurysm diameter and laboratory results. The morphology of human AAA vessel wall probes varies tremendously based on the grade of inflammation. This correlates with increasing intima/media thickness and upregulation of the vascular endothelial growth factor cascade but not with any clinical parameter or the aneurysm diameter. The phenotypic switch of vascular smooth muscle cells occurred regardless of the inflammatory state and expressional changes of the transcription factors Kruppel-like factor-4 and transforming growth factor-β lead to differential protein localization in aneurysmal compared with control arteries. These changes were in similar manner also observed in samples from popliteal artery aneurysms, which, however, showed a more homogenous phenotype. Heterogeneity of AAA vessel walls based on inflammatory morphology does not correlate with AAA diameter yet harbors specific implications for basic research and possible aneurysm detection. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Vascular wall flow-induced forces in a progressively enlarged aneurysm model.

PubMed

Neofytou, Panagiotis; Tsangaris, Sokrates; Kyriakidis, Michalis

2008-12-01

The current study is focused on the numerical investigation of the flow field induced by the unsteady flow in the vicinity of an abdominal aortic aneurysm model. The computational fluid dynamics code used is based on the finite volume method, and it has already been used in various bioflow studies. For modelling the rheological behaviour of blood, the Quemada non-Newtonian model is employed, which is suitable for simulating the two-phase character of blood namely a suspension of blood cells in plasma. For examining its non-Newtonian effects a comparison with a corresponding Newtonian flow is carried out. Furthermore, the investigation is focused on the distribution of the flow-induced forces on the interior wall of the aneurysm and in order to study the development of the distribution with the gradual enlargement of the aneurysm, three different degrees of aneurysm-growth have been assumed. Finally and for examining the effect of the distribution on the aneurysm growth, a comparison is made between the pressure and wall shear-stress distributions at the wall for each growth-degree.

The structure and material composition of ossified aortic valves identified using a set of scientific methods

NASA Astrophysics Data System (ADS)

Zeman, Antonín; Šmíd, Michal; Havelcová, Martina; Coufalová, Lucie; Kučková, Štěpánka; Velčovská, Martina; Hynek, Radovan

2013-11-01

Degenerative aortic stenosis has become a common and dangerous disease in recent decades. This disease leads to the mineralization of aortic valves, their gradual thickening and loss of functionality. We studied the detailed assessment of the proportion and composition of inorganic and organic components in the ossified aortic valve, using a set of analytical methods applied in science: polarized light microscopy, scanning electron microscopy, X-ray fluorescence, X-ray diffraction, gas chromatography/mass spectrometry and liquid chromatography-tandem mass spectrometry. The sample valves showed the occurrence of phosphorus and calcium in the form of phosphate and calcium carbonate, hydroxyapatite, fluorapatite and hydroxy-fluorapatite, with varying content of inorganic components from 65 to 90 wt%, and with phased development of degenerative disability. The outer layers of the plaque contained an organic component with peptide bonds, fatty acids, proteins and cholesterol. The results show a correlation between the formation of fluorapatite in aortic valves and in other parts of the human bodies, associated with the formation of bones.

M-Mode Echocardiographic Changes in Growing Beagles

PubMed Central

Diez-Prieto, Inmaculada; García-Rodríguez, M Belén; Ríos-Granja, M Angeles; Cano-Rábano, María J; Peña-Penabad, Marina; Pérez-García, Carlos C

2010-01-01

Heart growth in 6 female beagle dogs was measured by using M-mode echocardiography at 4, 7, 10, 13, 17, and 21 mo of age. The same 6 dogs were evaluated throughout the study to establish when cardiac development ends in this breed. The following parameters were measured during systole and diastole: left ventricle posterior wall thickness, interventricular septal thickness, left ventricular internal dimension, left atrial dimension during ventricular systole, aortic root dimension at end diastole, E-point to septal separation, left ventricular preejection period, ejection time of the left ventricular outflow, and time between the cessation and onset of the mitral inflow intervals. The percentage of the left ventricle posterior wall thickening, fractional shortening, ejection fraction, left ventricular end systolic and end-diastolic volumes, ratio of the left atrial dimension to aortic root dimension, and the Tei index of myocardial performance were calculated. The heart rate was measured by cardiac auscultation. The influence of ageing on each echocardiographic parameter and relationships with body weight and surface were studied. Results show that cardiac development in female beagles can be considered finished by the age of 1 y, perhaps as soon as 7 mo. The cardiac indexes studied were unaffected by the age and corporal dimensions, confirming the usefulness of these parameters for evaluating cardiac functionality alterations independent of a dog's age and body weight or surface area. PMID:20122313

Chromosomal mapping of quantitative trait loci controlling elastin content in rat aorta.

PubMed

Gauguier, Dominique; Behmoaras, Jacques; Argoud, Karène; Wilder, Steven P; Pradines, Christelle; Bihoreau, Marie Thérèse; Osborne-Pellegrin, Mary; Jacob, Marie Paule

2005-03-01

Extracellular matrix molecules such as elastin and collagens provide mechanical support to the vessel wall. In addition to its structural role, elastin is a regulator that maintains homeostasis through biologic signaling. Genetically determined minor modifications in elastin and collagen in the aorta could influence the onset and evolution of arterial pathology, such as hypertension and its complications. We previously demonstrated that the inbred Brown Norway (BN) rat shows an aortic elastin deficit in both abdominal and thoracic segments, partly because of a decrease in tropoelastin synthesis when compared with the LOU rat, that elastin gene polymorphisms in these strains do not significantly account for. After a genome-wide search for quantitative trait loci (QTL) influencing the aortic elastin, collagen, and cell protein contents in an F2 population derived from BN and LOU rats, we identified on chromosomes 2 and 14, 3 QTL specifically controlling elastin levels, and a further highly significant QTL on chromosome 17 linked to the level of cell proteins. We also mapped 3 highly significant QTL linked to body weight (on chromosomes 1 and 3) and heart weight (on chromosome 1) in the cross. This study demonstrates the polygenic control of the content of key components of the arterial wall. Such information represents a first step in understanding possible mechanisms involved in dysregulation of these parameters in arterial pathology.

Septation and separation within the outflow tract of the developing heart

PubMed Central

Webb, Sandra; Qayyum, Sonia R; Anderson, Robert H; Lamers, Wouter H; Richardson, Michael K

2003-01-01

The developmental anatomy of the ventricular outlets and intrapericardial arterial trunks is a source of considerable confusion. First, major problems exist because of the multiple names and definitions used to describe this region of the heart as it develops. Second, there is no agreement on the boundaries of the described components, nor on the number of ridges or cushions to be found dividing the outflow tract, and the pattern of their fusion. Evidence is also lacking concerning the role of the fused cushions relative to that of the so-called aortopulmonary septum in separating the intrapericardial components of the great arterial trunks. In this review, we discuss the existing problems, as we see them, in the context of developmental and postnatal morphology. We concentrate, in particular, on the changes in the nature of the wall of the outflow tract, which is initially myocardial throughout its length. Key features that, thus far, do not seem to have received appropriate attention are the origin, and mode of separation, of the intrapericardial portions of the arterial trunks, and the formation of the walls of the aortic and pulmonary valvar sinuses. Also as yet undetermined is the formation of the free-standing muscular subpulmonary infundibulum, the mechanism of its separation from the aortic valvar sinuses, and its differentiation, if any, from the muscular ventricular outlet septum. PMID:12739611

A two-system, single-analysis, fluid-structure interaction technique for modelling abdominal aortic aneurysms.

PubMed

Kelly, S C; O'Rourke, M J

2010-01-01

This work reports on the implementation and validation of a two-system, single-analysis, fluid-structure interaction (FSI) technique that uses the finite volume (FV) method for performing simulations on abdominal aortic aneurysm (AAA) geometries. This FSI technique, which was implemented in OpenFOAM, included fluid and solid mesh motion and incorporated a non-linear material model to represent AAA tissue. Fully implicit coupling was implemented, ensuring that both the fluid and solid domains reached convergence within each time step. The fluid and solid parts of the FSI code were validated independently through comparison with experimental data, before performing a complete FSI simulation on an idealized AAA geometry. Results from the FSI simulation showed that a vortex formed at the proximal end of the aneurysm during systolic acceleration, and moved towards the distal end of the aneurysm during diastole. Wall shear stress (WSS) values were found to peak at both the proximal and distal ends of the aneurysm and remain low along the centre of the aneurysm. The maximum von Mises stress in the aneurysm wall was found to be 408kPa, and this occurred at the proximal end of the aneurysm, while the maximum displacement of 2.31 mm occurred in the centre of the aneurysm. These results were found to be consistent with results from other FSI studies in the literature.

Decellularized aortic conduits: could their cryopreservation affect post-implantation outcomes? A morpho-functional study on porcine homografts.

PubMed

Gallo, Michele; Bonetti, Antonella; Poser, Helen; Naso, Filippo; Bottio, Tomaso; Bianco, Roberto; Paolin, Adolfo; Franci, Paolo; Busetto, Roberto; Frigo, Anna Chiara; Buratto, Edward; Spina, Michele; Marchini, Maurizio; Ortolani, Fulvia; Iop, Laura; Gerosa, Gino

2016-11-01

Decellularized porcine aortic valve conduits (AVCs) implanted in a Vietnamese Pig (VP) experimental animal model were matched against decellularized and then cryopreserved AVCs to assess the effect of cryopreservation on graft hemodynamic performance and propensity to in vivo repopulation by host's cells. VPs (n = 12) underwent right ventricular outflow tract substitution using AVC allografts and were studied for 15-month follow-up. VPs were randomized into two groups, receiving AVCs treated with decellularization alone (D; n = 6) or decellularization/cryopreservation (DC; n = 6), respectively. Serial echocardiography was carried out to follow up hemodynamic function. All explanted AVCs were processed for light and electron microscopy. No signs of dilatation, progressive stenosis, regurgitation, and macroscopic calcification were echocardiographically observed in both D and DC groups. Explanted D grafts exhibited near-normal features, whereas the presence of calcification, inflammatory infiltrates, and disarray of elastic lamellae occurred in some DC grafts. In the unaltered regions of AVCs from both groups, almost complete re-endothelialization was observed for both valve cusps and aorta walls. In addition, side-by-side repopulation by recipient's fibroblasts, myofibroblasts, and smooth muscle cells was paralleled by ongoing tissue remodeling, as revealed by the ultrastructural identification of typical canals of collagen fibrillogenesis and elastogenesis-related features. Incipient neo-vascularization and re-innervation of medial and adventitial tunicae of grafted aortic walls were also detected for both D and DC groups. Cryopreservation did not affect post-implantation AVC hemodynamic behavior and was topically propensive to cell repopulation and tissue renewal, although graft deterioration including calcification was present in several areas. Thus, these preliminary data provide essential information on feasibility of decellularization and cryopreservation coupling in the perspective of treatment optimization and subsequent clinical trials using similarly treated human allografts as innovative heart valve substitutes.

Descending aortic mechanics and atrial fibrillation: a two-dimensional speckle tracking transesophageal echocardiography study.

PubMed

Teixeira, Rogério; Monteiro, Ricardo; Dinis, Paulo; Santos, Maria José; Botelho, Ana; Quintal, Nuno; Cardim, Nuno; Gonçalves, Lino

2017-04-01

Vascular mechanics assessed with two-dimensional speckle tracking echocardiography (2D-STE) could be used as a new imaging surrogate of vascular stiffening. The CHA 2 DS 2 -VASc score is considered accurate as an estimate of stroke risk in non-valvular AF, although many potential stroke risk factors have not been included in this scoring method. The purpose of this research is to study the feasibility of evaluating vascular mechanics at the descending aorta in non-valvular AF patients using transesophageal 2D-STE and to analyze the association between descending aortic mechanics and stroke. We prospectively recruited a group of 44 patients referred for a transesophageal echocardiogram (TEE) in the context of cardioversion for non-valvular AF. A short-axis view of the descending aorta, one to two centimeters after the aortic arch was selected for the vascular mechanics assessment with the 2D-STE methodology. The vascular mechanics parameters analyzed were circumferential aortic strain (CAS) and early circumferential aortic strain rate (CASR). A clinical assessment was performed with focus on the past stroke history and the CHA 2 DS 2 -VASc score. The mean age of our cohort was 65 ± 13 years and 75% were men; AF was known for 2.8 ± 2.5 years and it was considered paroxystic in 41% of cases. Waveforms adequate for measuring 2D-STE were present in 85% of the 264 descending aortic wall segments. The mean CAS was 3.5 ± 1.2% and the mean CASR was 0.7 ± 0.3 s -1 . The inter- and intra-observer variability for aortic mechanics was considered adequate. The median CHA 2 DS 2 VASc score was 2 (2-3). As the score increased we noted that both the CAS (r = -0.38, P = 0.01) and the CASR (r = -0.42, P < 0.01) decreased. Over 16% of the AF patients had a past history of stroke. These patients had lower values of both descending aortic strain [2.2 (1.8-2.6) vs. 3.9 (3.3-4.9)%, P < 0.01] and strain rate [0.4 (0.3-0.4) vs. 0.7 (0.6-1.1) s -1 , P < 0.01]. CAS remained independently associated with a past history of stroke after adjustment for the CHA 2 DS 2 VASc score. Our data showed that non-valvular AF patients with a past history of stroke had lower values of aortic mechanics assessed with transesophageal 2D-STE.

Arterial waveform parameters in a large, population-based sample of adults: relationships with ethnicity and lifestyle factors.

PubMed

Sluyter, J D; Hughes, A D; Thom, S A McG; Lowe, A; Camargo, C A; Hametner, B; Wassertheurer, S; Parker, K H; Scragg, R K R

2017-05-01

Little is known about how aortic waveform parameters vary with ethnicity and lifestyle factors. We investigated these issues in a large, population-based sample. We carried out a cross-sectional analysis of 4798 men and women, aged 50-84 years from Auckland, New Zealand. Participants were 3961 European, 321 Pacific, 266 Maori and 250 South Asian people. We assessed modifiable lifestyle factors via questionnaires, and measured body mass index (BMI) and brachial blood pressure (BP). Suprasystolic oscillometry was used to derive aortic pressure, from which several haemodynamic parameters were calculated. Heavy alcohol consumption and BMI were positively related to most waveform parameters. Current smokers had higher levels of aortic augmentation index than non-smokers (difference=3.7%, P<0.0001). Aortic waveform parameters, controlling for demographics, antihypertensives, diabetes and cardiovascular disease (CVD), were higher in non-Europeans than in Europeans. Further adjustment for brachial BP or lifestyle factors (particularly BMI) reduced many differences but several remained. Despite even further adjustment for mean arterial pressure, pulse rate, height and total:high-density lipoprotein cholesterol, compared with Europeans, South Asians had higher levels of all measured aortic waveform parameters (for example, for backward pressure amplitude: β=1.5 mm Hg; P<0.0001), whereas Pacific people had 9% higher log e (excess pressure integral) (P<0.0001). In conclusion, aortic waveform parameters varied with ethnicity in line with the greater prevalence of CVD among non-white populations. Generally, this was true even after accounting for brachial BP, suggesting that waveform parameters may have increased usefulness in capturing ethnic variations in cardiovascular risk. Heavy alcohol consumption, smoking and especially BMI may partially contribute to elevated levels of these parameters.

Arterial waveform parameters in a large, population-based sample of adults: relationships with ethnicity and lifestyle factors

PubMed Central

Sluyter, J D; Hughes, A D; Thom, S A McG; Lowe, A; Camargo Jr, C A; Hametner, B; Wassertheurer, S; Parker, K H; Scragg, R K R

2017-01-01

Little is known about how aortic waveform parameters vary with ethnicity and lifestyle factors. We investigated these issues in a large, population-based sample. We carried out a cross-sectional analysis of 4798 men and women, aged 50–84 years from Auckland, New Zealand. Participants were 3961 European, 321 Pacific, 266 Maori and 250 South Asian people. We assessed modifiable lifestyle factors via questionnaires, and measured body mass index (BMI) and brachial blood pressure (BP). Suprasystolic oscillometry was used to derive aortic pressure, from which several haemodynamic parameters were calculated. Heavy alcohol consumption and BMI were positively related to most waveform parameters. Current smokers had higher levels of aortic augmentation index than non-smokers (difference=3.7%, P<0.0001). Aortic waveform parameters, controlling for demographics, antihypertensives, diabetes and cardiovascular disease (CVD), were higher in non-Europeans than in Europeans. Further adjustment for brachial BP or lifestyle factors (particularly BMI) reduced many differences but several remained. Despite even further adjustment for mean arterial pressure, pulse rate, height and total:high-density lipoprotein cholesterol, compared with Europeans, South Asians had higher levels of all measured aortic waveform parameters (for example, for backward pressure amplitude: β=1.5 mm Hg; P<0.0001), whereas Pacific people had 9% higher loge (excess pressure integral) (P<0.0001). In conclusion, aortic waveform parameters varied with ethnicity in line with the greater prevalence of CVD among non-white populations. Generally, this was true even after accounting for brachial BP, suggesting that waveform parameters may have increased usefulness in capturing ethnic variations in cardiovascular risk. Heavy alcohol consumption, smoking and especially BMI may partially contribute to elevated levels of these parameters. PMID:28004730

Segmental and age differences in the elastin network, collagen, and smooth muscle phenotype in the tunica media of the porcine aorta.

PubMed

Tonar, Zbyněk; Kubíková, Tereza; Prior, Claudia; Demjén, Erna; Liška, Václav; Králíčková, Milena; Witter, Kirsti

2015-09-01

The porcine aorta is often used in studies on morphology, pathology, transplantation surgery, vascular and endovascular surgery, and biomechanics of the large arteries. Using quantitative histology and stereology, we estimated the area fraction of elastin, collagen, alpha-smooth muscle actin, vimentin, and desmin within the tunica media in 123 tissue samples collected from five segments (thoracic ascending aorta; aortic arch; thoracic descending aorta; suprarenal abdominal aorta; and infrarenal abdominal aorta) of porcine aortae from growing domestic pigs (n=25), ranging in age from 0 to 230 days. The descending thoracic aorta had the greatest elastin fraction, which decreased proximally toward the aortic arch as well as distally toward the abdominal aorta. Abdominal aortic segments had the highest fraction of actin, desmin, and vimentin positivity and all of these vascular smooth muscle markers were lower in the thoracic aortic segments. No quantitative differences were found when comparing the suprarenal abdominal segments with the infrarenal abdominal segments. The area fraction of actin within the media was comparable in all age groups and it was proportional to the postnatal growth. Thicker aortic segments had more elastin and collagen with fewer contractile cells. The collagen fraction decreased from ascending aorta and aortic arch toward the descending aorta. By revealing the variability of the quantitative composition of the porcine aorta, the results are suitable for planning experiments with the porcine aorta as a model, i.e. power test analyses and estimating the number of samples necessary to achieving a desirable level of precision. The complete primary morphometric data, in the form of continuous variables, are made publicly available for biomechanical modeling of site-dependent distensibility and compliance of the porcine aorta. Copyright © 2015 Elsevier GmbH. All rights reserved.

Development of the Aortic Baroreflex in Microgravity

NASA Technical Reports Server (NTRS)

Shimizu, Tsuyoshi; Yamasaki, Masao; Waki, Hidefumi; Katsuda, Shin-ichiro; Oishi, Hirotaka; Katahira, Kiyoaki; Nagayama, Tadanori; Miyake, Masao; Miyamoto, Yukako

2003-01-01

Baroreceptors sense pressure in blood vessels and send this information to the brain. The primary baroreceptors are located in the main blood vessel leaving the heart (the aorta) and in the arteries in the neck (the carotid arteries). The brain uses information from the baroreceptors to determine whether blood pressure should be raised or lowered. These reflex responses are called baroreflexes. Changing position within a gravity field (i.e., moving from lying to sitting or standing) powerfully stimulates the baroreflexes. In weightlessness, the amount of stimuli that the baroreflexes receive is dramatically reduced. If this reduction occurs when the pathways that control the baroreflexes are being formed, it is possible that either the structure or function of the baroreceptors may be permanently changed. To study the effect of microgravity on structural and functional development of the aortic baroreflex system, we studied young rats (eight days old at launch) that flew on the Space Shuttle Columbia for 16 days. Six rats were studied on landing day; another six were studied after re-adapting to Earth's gravity for 30 days. On both landing day and 30 days after landing, we tested the sensitivity of the rats' baroreflex response. While the rats were anaesthetized, we recorded their arterial pressure, heart rate, and aortic nerve activity. After the tissues were preserved with perfusion fixation, we also examined the baroreflex structures. On landing day, we found that, compared to the controls, the flight rats had: fewer unmyelinated nerve fibers in their aortic nerves lower baroreflex sensitivity significantly lower contraction ability and wall tension of the aorta a reduced number of smooth muscle cells in the aorta. In the 30-day recovery group, the sensitivity of the baroreflex showed no difference between the flight rats and the control groups, although the unmyelinated fibers of the aortic nerve remained reduced in the flight rats. The results show that spaceflight does affect the development of the aortic baroreflex. The sensitivity of the reflex may be suppressed; however, the function of the blood pressure control system can re-adapt to Earth's gravity if the rats return before maturation. The structural differences in the input pathway of the reflex (Le., the reduction in nerve fibers) may remain permanently.

Pentosan polysulfate inhibits atherosclerosis in Watanabe heritable hyperlipidemic rabbits: differential modulation of metalloproteinase-2 and -9.

PubMed

Lupia, Enrico; Zheng, Feng; Grosjean, Fabrizio; Tack, Ivan; Doublier, Sophie; Elliot, Sharon J; Vlassara, Helen; Striker, Gary E

2012-02-01

Pentosan polysulfate (PPS), a heparinoid compound essentially devoid of anticoagulant activity, modulates cell growth and decreases inflammation. We investigated the effect of PPS on the progression of established atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. After severe atherosclerosis developed on an atherogenic diet, WHHL rabbits were treated with oral PPS or tap water for 1 month. The aortic intima-to-media ratio and macrophage infiltration were reduced, plaque collagen content was increased, and plaque fibrous caps were preserved by PPS treatment. Plasma lipid levels and post-heparin hepatic lipase activity remained unchanged. However, net collagenolytic activity in aortic extracts was decreased, and the levels of matrix metalloproteinase (MMP)-2 and tissue inhibitor of metalloproteinase (TIMP) activity were increased by PPS. Moreover, PPS treatment decreased tumor necrosis factor α (TNFα)-stimulated proinflammatory responses, in particular activation of nuclear factor-κB and p38, and activation of MMPs in macrophages. In conclusion, oral PPS treatment prevents progression of established atherosclerosis in WHHL rabbits. This effect may be partially mediated by increased MMP-2 and TIMP activities in the aortic wall and reduced TNFα-stimulated inflammation and MMP activation in macrophages. Thus, PPS may be a useful agent in inhibiting the progression of atherosclerosis.

Pentosan polysulfate inhibits atherosclerosis in Watanabe heritable hyperlipidemic rabbits: differential modulation of metalloproteinase-2 and -9

PubMed Central

Lupia, Enrico; Zheng, Feng; Grosjean, Fabrizio; Tack, Ivan; Doublier, Sophie; Elliot, Sharon J; Vlassara, Helen; Striker, Gary E

2013-01-01

Pentosan polysulfate (PPS), a heparinoid compound essentially devoid of anticoagulant activity, modulates cell growth and decreases inflammation. We investigated the effect of PPS on the progression of established atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. After severe atherosclerosis developed on an atherogenic diet, WHHL rabbits were treated with oral PPS or tap water for 1 month. The aortic intima-to-media ratio and macrophage infiltration were reduced, plaque collagen content was increased, and plaque fibrous caps were preserved by PPS treatment. Plasma lipid levels and post-heparin hepatic lipase activity remained unchanged. However, net collagenolytic activity in aortic extracts was decreased, and the levels of matrix metalloproteinase (MMP)-2 and tissue inhibitor of metalloproteinase (TIMP) activity were increased by PPS. Moreover, PPS treatment decreased tumor necrosis factor α (TNFα)-stimulated proinflammatory responses, in particular activation of nuclear factor-κB and p38, and activation of MMPs in macrophages. In conclusion, oral PPS treatment prevents progression of established atherosclerosis in WHHL rabbits. This effect may be partially mediated by increased MMP-2 and TIMP activities in the aortic wall and reduced TNFα-stimulated inflammation and MMP activation in macrophages. Thus, PPS may be a useful agent in inhibiting the progression of atherosclerosis. PMID:22042083

Immunohistochemical and ultrastructural detection of advanced glycation end products in atherosclerotic lesions of human aorta with a novel specific monoclonal antibody.

PubMed Central

Kume, S.; Takeya, M.; Mori, T.; Araki, N.; Suzuki, H.; Horiuchi, S.; Kodama, T.; Miyauchi, Y.; Takahashi, K.

1995-01-01

To elucidate the deposition of advanced glycation end products (AGEs) in aortic atherosclerosis, aortic walls were obtained from 25 autopsy cases and examined immunohistochemically and immunoelectron microscopically with a monoclonal antibody specific for AGEs, 6D12. Among the autopsy cases, atherosclerotic lesions were found in the aortas of 22 cases and were composed of diffuse intimal thickening, fatty streaks, atherosclerotic plaques, and/or complicated lesions. In these cases, intracellular AGE accumulation was demonstrated in the intimal lesions of aortic atherosclerosis in 12 cases. Compared with the diffuse intimal thickening, intracellular AGE accumulation was marked in the fatty streaks and atherosclerotic plaques. Immunohistochemical double staining with 6D12 and monoclonal antibodies for macrophages or muscle actin or a polyclonal antibody for scavenger receptors demonstrated that the AGE accumulation in macrophages or their related foam cells was marked in the diffuse intimal thickening and fatty streak lesions and that almost all macrophages and macrophage-derived foam cells possessed scavenger receptors. Immunoelectron microscopic observation revealed the localization of 6D12-positive reaction in lysosomal lipid vacuoles or electron-dense granules of the foam cells. These results indicate that AGE accumulation occurs in macrophages, smooth muscle cells, and their related foam cells. Images Figure 2 Figure 3 Figure 6 PMID:7545874

Endothelial MMP-9 drives the inflammatory response in abdominal aortic aneurysm (AAA).

PubMed

Ramella, Martina; Boccafoschi, Francesca; Bellofatto, Kevin; Md, Antonia Follenzi; Fusaro, Luca; Boldorini, Renzo; Casella, Francesco; Porta, Carla; Settembrini, Piergiorgio; Cannas, Mario

2017-01-01

Progression of abdominal aortic aneurysm (AAA) is typified by chronic inflammation and extracellular matrix (ECM) degradation of the aortic wall. Vascular inflammation involves complex interactions among inflammatory cells, endothelial cells (ECs), vascular smooth muscle cells (vSMCs), and ECM. Although vascular endothelium and medial neoangiogenesis play a key role in AAA, the molecular mechanisms underlying their involvement are only partially understood. In AAA biopsies, we found increased MMP-9, IL-6, and monocyte chemoattractant protein-1 (MCP-1), which correlated with massive medial neo-angiogenesis (C4d positive staining). In this study, we developed an in vitro model in order to characterize the role of endothelial matrix metalloproteinase-9 (e-MMP-9) as a potential trigger of medial disruption and in the inflammatory response bridging between ECs and vSMC. Lentiviral-mediated silencing of e-MMP-9 through RNA interference inhibited TNF-alpha-mediated activation of NF-κB in EA.hy926 human endothelial cells. In addition, EA.hy926 cells void of MMP-9 failed to migrate in a 3D matrix. Moreover, silenced EA.hy926 affected vSMC behavior in terms of matrix remodeling. In fact, also MMP-9 in vSMC resulted inhibited when endothelial MMP-9 was suppressed.

Continuous and Pulsatile Pediatric Ventricular Assist Device Hemodynamics with a Viscoelastic Blood Model

PubMed Central

Good, Bryan C.; Deutsch, Steven; Manning, Keefe B.

2015-01-01

Purpose To investigate the effects of pulsatile and continuous pediatric ventricular assist (PVAD) flow and pediatric blood viscoelasticity on hemodynamics in a pediatric aortic graft model. Methods Hemodynamic parameters of pulsatility, along with velocity and wall shear stress (WSS), are analyzed and compared between Newtonian and viscoelastic blood models at a range of physiological pediatric hematocrits using computational fluid dynamics. Results Both pulsatile and continuous PVAD flow lead to a decrease in pulsatility (surplus hemodynamic energy (SHE), ergs/cm3) compared to healthy aortic flow but with continuous PVAD pulsatility up to 2.4 times lower than pulsatile PVAD pulsatility at each aortic outlet. Significant differences are also seen between the two flow modes in velocity and WSS. The higher velocity jet during systole with pulsatile flow leads to higher WSSs at the anastomotic toe and at the aortic branch bifurcations. The lower velocity but continuous flow jet leads to a much different flow field and higher WSSs into diastole. Under a range of physiological pediatric hematocrit (20-60%), both velocity and WSS can vary significantly with the higher hematocrit blood model generally leading to higher peak WSSs but also lower WSSs in regions of flow separation. Conclusions The large decrease in pulsatility seen from continuous PVAD flow could lead to complications in pediatric vascular development while the high WSSs during peak systole from pulsatile PVAD flow could lead to blood damage. Both flow modes lead to similar regions prone to intimal hyperplasia (IH) resulting from low time-averaged WSS (TAWSS) and high oscillatory shear index (OSI). PMID:26643646

Can Intestinal Phosphate Binding or Inhibition of Hydroxyapatite Growth in the Vascular Wall Halt the Progression of Established Aortic Calcification in Chronic Kidney Disease?

PubMed

Neven, Ellen; Opdebeeck, Britt; De Maré, Annelies; Bashir-Dar, Rida; Dams, Geert; Marynissen, Rita; Behets, Geert J; Verhulst, Anja; Riser, Bruce L; D'Haese, Patrick C

2016-11-01

Vascular calcification significantly contributes to mortality in chronic kidney disease (CKD) patients. Sevelamer and pyrophosphate (PPi) have proven to be effective in preventing vascular calcification, the former by controlling intestinal phosphate absorption, the latter by directly interfering with the hydroxyapatite crystal formation. Since most patients present with established vascular calcification, it is important to evaluate whether these compounds may also halt or reverse the progression of preexisting vascular calcification. CKD and vascular calcification were induced in male Wistar rats by a 0.75 % adenine low protein diet for 4 weeks. Treatment with PPi (30 or 120 µmol/kg/day), sevelamer carbonate (1500 mg/kg/day) or vehicle was started at the time point at which vascular calcification was present and continued for 3 weeks. Hyperphosphatemia and vascular calcification developed prior to treatment. A significant progression of aortic calcification in vehicle-treated rats with CKD was observed over the final 3-week period. Sevelamer treatment significantly reduced further progression of aortic calcification as compared to the vehicle control. No such an effect was seen for either PPi dose. Sevelamer but not PPi treatment resulted in an increase in both osteoblast and osteoid perimeter. Our study shows that sevelamer was able to reduce the progression of moderate to severe preexisting aortic calcification in a CKD rat model. Higher doses of PPi may be required to induce a similar reduction of severe established arterial calcification in this CKD model.

New classification of geometric ventricular patterns in severe aortic stenosis: Could it be clinically useful?

PubMed

Di Nora, Concetta; Cervesato, Eugenio; Cosei, Iulian; Ravasel, Andreea; Popescu, Bogdan A; Zito, Concetta; Carerj, Scipione; Antonini-Canterin, Francesco; Popescu, Andreea C

2018-04-16

In severe aortic stenosis, different left ventricle (LV) remodeling patterns as a response to pressure overload have distinct hemodynamic profiles, cardiac function, and outcomes. The most common classification considers LV relative wall thickness and LV mass index to create 4 different groups. A new classification including also end-diastolic volume index has been recently proposed. To describe the prevalence of the newly identified remodeling patterns in patients with severe aortic stenosis and to evaluate their clinical relevance according to symptoms. We analyzed 286 consecutive patients with isolated severe aortic stenosis. Current guidelines were used for echocardiographic evaluation. Symptoms were defined as the presence of angina, syncope, or NYHA class III-IV. The mean age was 75 ± 9 years, 156 patients (54%) were men, while 158 (55%) were symptomatic. According to the new classification, the most frequent remodeling pattern was concentric hypertrophy (57.3%), followed by mixed (18.9%) and dilated hypertrophy (8.4%). There were no patients with eccentric remodeling; only 4 patients had a normalLV geometry. Symptomatic patients showed significantly more mixed hypertrophy (P < .05), while the difference regarding the prevalence of the other patterns was not statistically significant. When we analyzed the distribution of the classic 4 patterns stratified by the presence of symptoms, however, we did not find a significant difference (P = .157). The new classification had refined the description of different cardiac geometric phenotypes that develop as a response to pressure overload. It might be superior to the classic 4 patterns in terms of association with symptoms. © 2018 Wiley Periodicals, Inc.

A new method for precise determination of endograft position and apposition in the aortic neck after endovascular aortic aneurysm repair.

PubMed

VAN Noort, Kim; Schuurmann, Richte C; Slump, Cornelis H; Vos, Jan A; Devries, Jean P

2016-10-01

Follow-up imaging after endovascular aortic aneurysm repair (EVAR) focuses on detection of gross abnormalities: endoleaks and significant (>10 mm) migration. Precise determination of endograft position and wall apposition may predict late complications. We present a new measurement method to determine precise position and apposition of endografts in the aortic neck. Four patients were selected from our EVAR database. These patients had late (>1 year) type IA endoleak or >1 cm endograft migration. Twenty patients with uneventful follow-up were measured as controls. The new software adds six parameters to define endograft position and neck apposition: fabric distance to renal arteries, tilt, endograft expansion (% of the maximum original diameter), neck surface, apposition surface, and shortest apposition length. These parameters were determined on preoperative and all available postoperative CT-scans, to detect subtle changes during follow-up. All patients with endoleak or migration had increases in fabric distance, tilt, or endograft expansion or decrease of apposition surface. Changes occurred at least one CT scan before the endoleak or migration was noted in the CT reports. The patient without complications showed no changes in position or apposition during follow-up. The new measurement method detected subtle changes in endograft position and apposition during CT follow-up, not recognized initially. It can potentially determine endograft movements and decrease of apposition surface before they lead to complications like type IA endoleaks or uncorrectable migration. A larger follow-up study comparing complicated and non-complicated EVAR patients is needed to corroborate these results.

Don't Forget the Abdominal Wall: Imaging Spectrum of Abdominal Wall Injuries after Nonpenetrating Trauma.

PubMed

Matalon, Shanna A; Askari, Reza; Gates, Jonathan D; Patel, Ketan; Sodickson, Aaron D; Khurana, Bharti

2017-01-01

Abdominal wall injuries occur in nearly one of 10 patients coming to the emergency department after nonpenetrating trauma. Injuries range from minor, such as abdominal wall contusion, to severe, such as abdominal wall rupture with evisceration of abdominal contents. Examples of specific injuries that can be detected at cross-sectional imaging include abdominal muscle strain, tear, or hematoma, including rectus sheath hematoma (RSH); traumatic abdominal wall hernia (TAWH); and Morel-Lavallée lesion (MLL) (closed degloving injury). These injuries are often overlooked clinically because of (a) a lack of findings at physical examination or (b) distraction by more-severe associated injuries. However, these injuries are important to detect because they are highly associated with potentially grave visceral and vascular injuries, such as aortic injury, and because their detection can lead to the diagnosis of these more clinically important grave traumatic injuries. Failure to make a timely diagnosis can result in delayed complications, such as bowel hernia with potential for obstruction or strangulation, or misdiagnosis of an abdominal wall neoplasm. Groin injuries, such as athletic pubalgia, and inferior costochondral injuries should also be considered in patients with abdominal pain after nonpenetrating trauma, because these conditions may manifest with referred abdominal pain and are often included within the field of view at cross-sectional abdominal imaging. Radiologists must recognize and report acute abdominal wall injuries and their associated intra-abdominal pathologic conditions to allow appropriate and timely treatment. © RSNA, 2017.

Guidance of aortic ablation using optical coherence tomography.

PubMed

Patel, Nirlep A; Li, Xingde; Stamper, Debra L; Fujimoto, James G; Brezinski, Mark E

2003-04-01

There is a significant need for an imaging modality that is capable of providing guidance for intravascular procedures, as current technologies suffer from significant limitations. In particular, laser ablation of in-stent restenosis, revascularization of chronic total occlusions, and pulmonary vein ablation could benefit from guidance. Optical coherence tomography (OCT), a recently introduced technology, is similar to ultrasound except that it measures the back-reflection of infrared light instead of sound. This study examines the ability of OCT to guide vascular laser ablation. Aorta samples underwent laser ablation using an argon laser at varying power outputs and were monitored with OCT collecting images at 4 frames. Samples were compared to the corresponding histopathology. Arterial layers could be differentiated in the images sequences. This allowed correlation of changes in the OCT image with power and duration in addition to histopathology. OCT provides real-time guidance of arterial ablation. At 4 frames, OCT was successfully able to show the microstructural changes in the vessel wall during laser ablation. Since current ablation procedures often injure surrounding tissue, the ability to minimize collateral damage to the adjoining tissue represents a useful advantage of this system. This study suggests a possible role for OCT in the guidance of intravascular procedures.

Hepatic steatosis is associated with aortic valve sclerosis in the general population: the Study of Health in Pomerania (SHIP).

PubMed

Markus, Marcello Ricardo Paulista; Baumeister, Sebastian Edgar; Stritzke, Jan; Dörr, Marcus; Wallaschofski, Henri; Völzke, Henry; Lieb, Wolfgang

2013-07-01

We aimed to analyze the association between hepatic steatosis and aortic valve sclerosis in the general population. Cross-sectional data of 2212 men and women, aged 45 to 81 years, from the baseline examination of the population-based Study of Health in Pomerania (SHIP-0) were analyzed. Hepatic steatosis was primarily defined as the presence of a hyperechogenic ultrasound pattern of the liver. Aortic valve sclerosis was determined by echocardiography. In our sample, hepatic steatosis was present in 877 (39.7%) individuals. Among participants with hepatic steatosis, aortic valve sclerosis was more common (n=323; 36.8%) compared with participants without hepatic steatosis (n=379; 28.4%; P<0.001). After adjustment for potential confounders, individuals with hepatic steatosis had 33% higher odds of aortic valve sclerosis compared with those without hepatic steatosis (95% confidence interval, 6%-66%; P=0.014). Additional adjustment for high-sensitive C-reactive protein, serum ferritin levels, and white blood cells slightly reduced the association to 32% (95% confidence interval, 4%-66%; P=0.021). Our findings add evidence that hepatic steatosis and aortic valve sclerosis are interrelated after adjustment for major confounders. The release of proatherogenic substances by the steatotic liver or its contribution to insulin resistance and dyslipidemia may contribute to the development of calcification and sclerosis of the aortic valve.

Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2 Diabetes Mellitus.

PubMed

Raaz, Uwe; Schellinger, Isabel N; Chernogubova, Ekaterina; Warnecke, Christina; Kayama, Yosuke; Penov, Kiril; Hennigs, Jan K; Salomons, Florian; Eken, Suzanne; Emrich, Fabian C; Zheng, Wei H; Adam, Matti; Jagger, Ann; Nakagami, Futoshi; Toh, Ryuji; Toyama, Kensuke; Deng, Alicia; Buerke, Michael; Maegdefessel, Lars; Hasenfuß, Gerd; Spin, Joshua M; Tsao, Philip S

2015-08-28

Accelerated arterial stiffening is a major complication of diabetes mellitus with no specific therapy available to date. The present study investigates the role of the osteogenic transcription factor runt-related transcription factor 2 (Runx2) as a potential mediator and therapeutic target of aortic fibrosis and aortic stiffening in diabetes mellitus. Using a murine model of type 2 diabetes mellitus (db/db mice), we identify progressive structural aortic stiffening that precedes the onset of arterial hypertension. At the same time, Runx2 is aberrantly upregulated in the medial layer of db/db aortae, as well as in thoracic aortic samples from patients with type 2 diabetes mellitus. Vascular smooth muscle cell-specific overexpression of Runx2 in transgenic mice increases expression of its target genes, Col1a1 and Col1a2, leading to medial fibrosis and aortic stiffening. Interestingly, increased Runx2 expression per se is not sufficient to induce aortic calcification. Using in vivo and in vitro approaches, we further demonstrate that expression of Runx2 in diabetes mellitus is regulated via a redox-sensitive pathway that involves a direct interaction of NF-κB with the Runx2 promoter. In conclusion, this study highlights Runx2 as a previously unrecognized inducer of vascular fibrosis in the setting of diabetes mellitus, promoting arterial stiffness irrespective of calcification. © 2015 American Heart Association, Inc.

In-vitro analysis of early calcification in aortic valvular interstitial cells using Laser-Induced Breakdown Spectroscopy (LIBS).

PubMed

Davari, Seyyed Ali; Masjedi, Shirin; Ferdous, Zannatul; Mukherjee, Dibyendu

2018-01-01

Calcific aortic valve disease (CAVD) is a major cardiovascular disorder caused by osteogenic differentiation of valvular interstitial cells (VICs) within aortic valves. Conventional methods like colorimetric assays and histology fail to detect small calcium depositions during in-vitro VIC cultures. Laser-induced breakdown spectroscopy (LIBS) is a robust analytical tool used for inorganic materials characterizations, but relatively new to biomedical applications. We employ LIBS, for the first time, for quantitative in-vitro detection of calcium depositions in VICs at various osteogenic differentiation stages. VICs isolated from porcine aortic valves were cultured in osteogenic media over various days. Colorimetric calcium assays based on arsenazo dye and Von Kossa staining measured the calcium depositions within VICs. Simultaneously, LIBS signatures for Ca I (422.67 nm) atomic emission lines were collected for estimating calcium depositions in lyophilized VIC samples. Our results indicate excellent linear correlation between the calcium assay and our LIBS measurements. Furthermore, unlike the assay results, the LIBS results could resolve calcium signals from cell samples with as early as 2 days of osteogenic culture. Quantitatively, the LIBS measurements establish the limit of detection for calcium content in VICs to be ∼0.17±0.04 μg which indicates a 5-fold improvement over calcium assay. Picture: Quantitative LIBS enables in-vitro analysis for early stage detection of calcium deposition within aortic valvular interstitial cells (VICs). © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

CXCL16/CXCR6-mediated adhesion of human peripheral blood mononuclear cells to inflamed endothelium.

PubMed

Linke, Bona; Meyer Dos Santos, Sascha; Picard-Willems, Bettina; Keese, Michael; Harder, Sebastian; Geisslinger, Gerd; Scholich, Klaus

2017-06-21

The endothelial chemokine CXC motif ligand 16 (CXCL16) is involved in the recruitment and firm adhesion of CXCR6 + cells to the atherosclerosis-prone aortic vessel wall. Recently we showed that CXCR6 + platelets from flowing blood attach to CXCL16 expressed by activated endothelium on the luminal side of the blood vessel. With this study we supplement these findings with the observation that platelets bound to the inflamed endothelium are presenting CXCR6 to CXCL16-positive peripheral blood mononuclear cells (PBMCs) and, thus, are mediating an increased adhesion of PBMCs to the arterial wall. Furthermore we identified endothelial CXCL16 as an important adhesion molecule promoting the firm adhesion of CXCR6-positive PBMCs to inflamed endothelium. Our results demonstrate that endothelial CXCL16 as well as platelet CXCR6 are acting as potent PBMC-adhesion ligands, inducing PBMC-adhesion to the atherosclerosis-prone vessel wall and thus promoting the progression of atherosclerosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Selective common and uncommon imaging manifestations of blunt nonaortic chest trauma: when time is of the essence.

PubMed

Altoos, Rola; Carr, Robert; Chung, Jonathan; Stern, Eric; Nevrekar, Dipti

2015-01-01

This is a pictorial essay in which we review and illustrate a variety of thoracic injuries related to blunt trauma. Non-aortic blunt thoracic trauma can be divided anatomically into injuries of the chest wall, lungs, pleura, mediastinum, and diaphragm. Some injuries involve more than one anatomic compartment, and multiple injuries commonly coexist. This article provides common imaging findings and discussion of both common and uncommon but critical thoracic injuries encountered. Published by Elsevier Inc.

Rationale and Design of the ARREST Trial Investigating Mesenchymal Stem Cells in the Treatment of Small Abdominal Aortic Aneurysm.

PubMed

Wang, S Keisin; Green, Linden A; Gutwein, Ashley R; Drucker, Natalie A; Motaganahalli, Raghu L; Fajardo, Andres; Babbey, Clifford M; Murphy, Michael P

2018-02-01

Abdominal aortic aneurysms (AAAs) are a major source of morbidity and mortality despite continuing advances in surgical technique and care. Although the inciting factors for AAA development continue to be elusive, accumulating evidence suggests a significant periaortic inflammatory response leading to degradation and dilation of the aortic wall. Previous human trials have demonstrated safety and efficacy of mesenchymal stem cells (MSCs) in the treatment of inflammation-related pathologies such as rheumatoid arthritis, graft versus host disease, and transplant rejection. Therefore, herein, we describe the Aortic Aneurysm Repression with Mesenchymal Stem Cells (ARREST) trial, a phase I investigation into the safety of MSC infusion for patients with small AAA and the cells' effects on modulation of AAA-related inflammation. ARREST is a phase I, single-center, double-blind, randomized controlled trial (RCT) investigating infusion both dilute and concentrated MSCs compared to placebo in 36 small AAA (35-45 mm) patients. Subjects will be followed by study personnel for 12 months to ascertain incidence of adverse events, immune cell phenotype expression, peripheral cytokine profile, and periaortic inflammation. Maximum transverse aortic diameter will be assessed regularly for 5 years by a combination of computed tomography and duplex sonography. Four patients have thus far been enrolled, randomized, and treated per protocol. We anticipate the conclusion of the treatment phase within the next 24 months with ongoing long-term follow-up. ARREST will be pivotal in assessing the safety of MSC infusion and provide preliminary data on the ability of MSCs to favorably modulate the pathogenic AAA host immune response. The data gleaned from this phase I trial will provide the groundwork for a larger, phase III RCT which may provide the first pharmaceutical intervention for AAA. Copyright © 2017 Elsevier Inc. All rights reserved.

Novel multi-dimensional modelling for surgical planning of acute aortic dissection type A based on computed tomography scan.

PubMed

Hossien, Abdullrazak; Gelsomino, Sandro; Mochtar, Baheramsjah; Maessen, Jos G; Sardari Nia, Peyman

2015-11-01

Acute type A aortic dissection (TAAD) is a life-threatening emergency and requires immediate surgical intervention. We propose a novel finite element multi-dimensional modelling (FE-MDM) technique to identify aortic tears preoperatively to aid surgical preplanning. Thirty-two patients with TAAD were included in this retrospective study. Computed tomography (CT) scans were imported using the segmentation software and reconstruction resulted in modelling of single TAAD components: aortic wall, false lumen, true lumen, gap in the flap and blood in both lumens. CT scans were processed by interpreters who were blinded to the clinical data and then were compared with operative findings. The models were assessed and compared regarding localization and size of the entry tear with the intraoperative findings. Image set data were retrieved from CT scans. Surgical inspection confirmed the localization of the tear obtained by the model in all patients with a 100% chance prediction (P < 0.0001) in all patients. With the simulation of the guided-cannulation, it was possible to place the cannula in the ascending aorta in 100% of patients (P < 0.0001 vs surgery). Using the virtual volume model, the chance of inserting into the false lumen was 0% (P < 0.0001). There was a strong correlation between the virtual volume model and cannulation in the true lumen (r = 0.88, P < 0.0001). The FE-MDM technique of aortic dissection is helpful in identifying the site of the tear and may be considered as an additional tool in surgical preplanning. It may also enhance the efficiency of deep hypothermic circulatory arrest in patients with single entry sites in the ascending aorta and it may facilitate direct cannulation of the ascending aorta. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Aortic elasticity indices by magnetic resonance predict progression of ascending aorta dilation.

PubMed

Aquaro, Giovanni Donato; Briatico Vangosa, Alessandra; Toia, Patrizia; Barison, Andrea; Ait-Ali, Lamia; Midiri, Massimo; Cotroneo, Antonio Raffaele; Emdin, Michele; Festa, Pierluigi

2017-04-01

Aortic distensibility and pulse-wave velocity (PWV) are under investigation as parameters by which to evaluate the indication for ascending aorta (AA) replacement. The maximum rate of systolic distension (MRSD) was proposed as a new index of aortic elasticity. The aim of this study was to assess the role of aortic elasticity parameters to predict AA growth rates in patients with AA dilation (AAD). Magnetic resonance imaging (MRI) was performed annually in 65 patients with AA dilation (median follow-up 17 months; 25-75th percentile; range 12-30 months). A significant increase in AA diameter was defined as a ≥2-mm increase. An increase in AA diameter was found in 42 (68 %) patients (AAD+ group) and absent in 20. Median increase was 0.16 (25-75th percentile; range 0.32-0.7) mm/month. The AAD+ group had a lower MRSD (4.6 ± 2.2 vs 7.4 ± 2.0, p < 0.001) but the same PWV and distensibility. MRSD showed 93.7 % specificity and 75.6 % sensitivity for prediction of increase. Patients with MRSD ≤ 6 had lower progression-free survival times (p < 0.002). After a follow-up of 4.1 years, patients who underwent surgical therapy had lower MRSD and distensibility than others. MRSD is an index of aorta elastic properties and is a valuable predictor for progression in AAD. • MRI-derived parameters of aortic wall elasticity predict progression of ascending aorta dilation. • Maximal rate of systolic distension (MRSD) was the best predictor of progression. • Patients with MRSD ≤ 6 had lower progression-free survival (PFS) times. • Patients who underwent surgical therapy had lower MRSD and distensibility. • MRI-derived parameters identify patients with fast progression of Ascending Aorta Dilation.

The early and midterm function of decellularized aortic valve allografts.

PubMed

da Costa, Francisco D A; Costa, Ana Claudia B A; Prestes, Roberta; Domanski, Ana Carolina; Balbi, Eduardo Mendel; Ferreira, Andreia D A; Lopes, Sergio Veiga

2010-12-01

This study evaluates the early and midterm results of decellularized aortic valve allografts (DAVA) as an aortic valve replacement. Between October 2005 and February 2010, 41 patients, 28 of whom were male, with a median age of 34 years (range, 0.1 to 71), had aortic valve replacement with DAVA. Decellularization was obtained with a 0.1% sodium dodecyl sulfate solution. Postoperative evaluation was performed with serial echocardiograms, magnetic resonance imaging, and multislice computed tomography studies to evaluate valve hemodynamics, allograft conduit dimensions, and calcification scores. There were 3 early deaths and 1 late death, with a mean follow-up of 19 months (range, 1 to 53). There was 1 reoperation due to a failed mitral valve repair. By echocardiography in all patients, the median immediate postoperative peak gradient was 7 mm Hg (range, 1 to 26 mm Hg), and at last follow-up it was 4 mm Hg (range, 1 to 16 mm Hg); valvular regurgitation was graded as none or trivial in all but 1 patient, who had a regurgitation graded as mild to moderate. By magnetic resonance imaging (n = 4), mean root dimensions were stable at the annulus (24 mm), sinus of Valsalva (33 mm), and sinotubular junction (28 mm). By computed tomography (n = 22), there was only discrete conduit calcification (median calcium score 63 Hounsfield units [HU]; range, 0 to 894 HU) to 3 years of follow-up. Conduit biopsy in the patient who underwent reoperation demonstrated well-preserved wall structure, absence of calcification, and limited in vivo host repopulation. The early and midterm results with DAVA demonstrated stable structural integrity, low rate of calcification, and adequate hemodynamics. Although longer periods of observation are necessary, DAVA appears to be a promising alternative for aortic valve replacement in selected patients. Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Role of diastolic function indices in the risk stratification of patients with mixed aortic valve disease.

PubMed

Egbe, Alexander C; Khan, Arooj R; Boler, Amber; Said, Sameh M; Geske, Jeffrey B; Miranda, William R; Akintoye, Emmanuel; Connolly, Heidi M; Warnes, Carole A; Oh, Jae K

2018-06-01

Determine the role of diastolic function indices in pre-operative and post-operative risk stratification in patients with moderate mixed aortic valve disease (MAVD). A retrospective study was conducted of asymptomatic patients with moderate MAVD (a combination of moderate aortic stenosis and moderate aortic regurgitation) and an ejection fraction of 50% or more who were followed up at Mayo Clinic from 1 January 2004, to 31 December 2013. A pre-requisite for inclusion in the study was assessment of diastolic function involving at least three of the following indices: tissue Doppler early diastolic velocity (e'), mitral inflow early velocity (E), tricuspid regurgitation velocity, and left atrial volume index. Primary endpoints were aortic valve replacement (AVR) or cardiac death while secondary endpoints were cardiovascular adverse events (CAEs) after AVR. We defined CAEs as stroke, heart failure hospitalization, severe left ventricular dysfunction, and cardiac death. There were 214 patients (age 61 ± 8 years, men 146 [68%]) followed for 6.1 ± 2.3 years during which 162 (76%) AVRs and 11 (5%) cardiac deaths occurred. The multivariable risk factors for cardiac death or AVR were relative wall thickness (RWT) > 0.42 [hazard ratio (HR), 1.88 [95% CI, 1.28-2.59]; P = 0.001] and average E/e' >14 (HR, 1.94 [95% CI, 1.29-3.01]; P = 0.02). Freedom from CAE after AVR was significantly lower in the patients with baseline RWT >0.42 or mean E/e' >14 than the other patients: 79% (95% CI 74-83%) vs. 94% (95% CI 89-98%) at 3 years (P = 0.03). The presence of RWT >0.42 or E/e' >14 identifies a high-risk patient subset whose risk for cardiovascular morbidities persists even after AVR.

Aortic Arch Morphology and Aortic Length in Patients with Dissection, Traumatic, and Aneurysmal Disease.

PubMed

Alberta, H B; Takayama, T; Smits, T C; Wendorff, B B; Cambria, R P; Farber, M A; Jordan, W D; Patel, V; Azizzadeh, A; Rovin, J D; Matsumura, J S

2015-12-01

To assess aortic arch morphology and aortic length in patients with dissection, traumatic injury, and aneurysm undergoing TEVAR, and to identify characteristics specific to different pathologies. This was a retrospective analysis of the aortic arch morphology and aortic length of dissection, traumatic injury, and aneurysmal patients. Computed tomography imaging was evaluated of 210 patients (49 dissection, 99 traumatic injury, 62 aneurysm) enrolled in three trials that received the conformable GORE TAG thoracic endoprosthesis. The mean age of trauma patients was 43 ± 19.6 years, 57 ± 11.7 years for dissection and 72 ± 9.6 years for aneurysm patients. A standardized protocol was used to measure aortic arch diameter, length, and take-off angle and clockface orientation of branch vessels. Differences in arch anatomy and length were assessed using ANOVA and independent t tests. Of the 210 arches evaluated, 22% had arch vessel common trunk configurations. The aortic diameter and the distance from the left main coronary (LMC) to the left common carotid (LCC) were greater in dissection patients than in trauma or aneurysm patients (p < .001). Aortic diameter in aneurysm patients was greater compared with trauma patients (p < .05). The distances from the branch vessels to the celiac artery (CA) were greater in dissection and aneurysm patients than in trauma patients (p < .001). The take-off angle of the innominate (I), LCCA, and left subclavian (LS) were greater, between 19% and 36%, in trauma patients than in dissection and aneurysm patients (p < .001). Clockface orientation of the arch vessels varies between pathologies. Arch anatomy has significant morphologic differences when comparing aortic pathologies. Describing these differences in a large sample of patients is beneficial for device designs and patient selection. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Bacteria and bacterial DNA in atherosclerotic plaque and aneurysmal wall biopsies from patients with and without periodontitis

PubMed Central

Armingohar, Zahra; Jørgensen, Jørgen J.; Kristoffersen, Anne Karin; Abesha-Belay, Emnet; Olsen, Ingar

2014-01-01

Background Several studies have reported an association between chronic periodontitis (CP) and cardiovascular diseases. Detection of periodontopathogens, including red complex bacteria (RCB), in vascular lesions has suggested these bacteria to be involved in the pathogenesis of atherosclerosis and abdominal aortic aneurysms. Objective In this study, we investigate bacteria and their DNA in vascular biopsies from patients with vascular diseases (VD; i.e. abdominal aortic aneurysms, atherosclerotic carotid, and common femoral arteries), with and without CP. Methods DNA was extracted from vascular biopsies selected from 40 VD patients: 30 with CP and 10 without CP. The V3-V5 region of the 16S rDNA (V3-V5) was polymerase chain reaction (PCR)-amplified, and the amplicons were cloned into Escherichia coli, sequenced, and classified (GenBank and the Human Oral Microbiome database). Species-specific primers were used for the detection of Porphyromonas gingivalis. In addition, 10 randomly selected vascular biopsies from the CP group were subjected to scanning electron microscopy (SEM) for visualization of bacteria. Checkerboard DNA–DNA hybridization was performed to assess the presence of RCB in 10 randomly selected subgingival plaque samples from CP patients. Results A higher load and mean diversity of bacteria were detected in vascular biopsies from VD patients with CP compared to those without CP. Enterobacteriaceae were frequently detected in vascular biopsies together with cultivable, commensal oral, and not-yet-cultured bacterial species. While 70% of the subgingival plaque samples from CP patients showed presence of RCB, only P. gingivalis was detected in one vascular biopsy. Bacterial cells were seen in all 10 vascular biopsies examined by SEM. Conclusions A higher bacterial load and more diverse colonization were detected in VD lesions of CP patients as compared to patients without CP. This indicated that a multitude of bacterial species both from the gut and the oral cavity, rather than exclusively periodontopathogens, may be involved as additional risk factors in the pathogenesis of VD. PMID:25006361

Spaceflight Affects Postnatal Development of the Aortic Wall in Rats

PubMed Central

Yamasaki, Masao; Waki, Hidefumi; Miyake, Masao; Nagayama, Tadanori; Miyamoto, Yukako; Wago, Haruyuki; Okouchi, Toshiyasu; Shimizu, Tsuyoshi

2014-01-01

We investigated effect of microgravity environment during spaceflight on postnatal development of the rheological properties of the aorta in rats. The neonate rats were randomly divided at 7 days of age into the spaceflight, asynchronous ground control, and vivarium control groups (8 pups for one dam). The spaceflight group rats at 9 days of age were exposed to microgravity environment for 16 days. A longitudinal wall strip of the proximal descending thoracic aorta was subjected to stress-strain and stress-relaxation tests. Wall tensile force was significantly smaller in the spaceflight group than in the two control groups, whereas there were no significant differences in wall stress or incremental elastic modulus at each strain among the three groups. Wall thickness and number of smooth muscle fibers were significantly smaller in the spaceflight group than in the two control groups, but there were no significant differences in amounts of either the elastin or collagen fibers among the three groups. The decreased thickness was mainly caused by the decreased number of smooth muscle cells. Plastic deformation was observed only in the spaceflight group in the stress-strain test. A microgravity environment during spaceflight could affect postnatal development of the morphological and rheological properties of the aorta. PMID:25210713

Flow and wall shear stress characterization after endovascular aneurysm repair and endovascular aneurysm sealing in an infrarenal aneurysm model.

PubMed

Boersen, Johannes T; Groot Jebbink, Erik; Versluis, Michel; Slump, Cornelis H; Ku, David N; de Vries, Jean-Paul P M; Reijnen, Michel M P J

2017-12-01

Endovascular aneurysm repair (EVAR) with a modular endograft has become the preferred treatment for abdominal aortic aneurysms. A novel concept is endovascular aneurysm sealing (EVAS), consisting of dual endoframes surrounded by polymer-filled endobags. This dual-lumen configuration is different from a bifurcation with a tapered trajectory of the flow lumen into the two limbs and may induce unfavorable flow conditions. These include low and oscillatory wall shear stress (WSS), linked to atherosclerosis, and high shear rates that may result in thrombosis. An in vitro study was performed to assess the impact of EVAR and EVAS on flow patterns and WSS. Four abdominal aortic aneurysm phantoms were constructed, including three stented models, to study the influence of the flow divider on flow (Endurant [Medtronic, Minneapolis, Minn], AFX [Endologix, Irvine, Calif], and Nellix [Endologix]). Experimental models were tested under physiologic resting conditions, and flow was visualized with laser particle imaging velocimetry, quantified by shear rate, WSS, and oscillatory shear index (OSI) in the suprarenal aorta, renal artery (RA), and common iliac artery. WSS and OSI were comparable for all models in the suprarenal aorta. The RA flow profile in the EVAR models was comparable to the control, but a region of lower WSS was observed on the caudal wall compared with the control. The EVAS model showed a stronger jet flow with a higher shear rate in some regions compared with the other models. Small regions of low WSS and high OSI were found near the distal end of all stents in the common iliac artery compared with the control. Maximum shear rates in each region of interest were well below the pathologic threshold for acute thrombosis. The different stent designs do not influence suprarenal flow. Lower WSS is observed in the caudal wall of the RA after EVAR and a higher shear rate after EVAS. All stented models have a small region of low WSS and high OSI near the distal outflow of the stents. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Structure, Mechanics, and Histology of Intraluminal Thrombi in Abdominal Aortic Aneurysms.

PubMed

Tong, Jianhua; Holzapfel, Gerhard A

2015-07-01

It has been recognized that the intraluminal thrombus (ILT) is a biologically active material contributing in the progression and rupture of abdominal aortic aneurysms (AAAs). To advance our understanding of the potential role of ILT in the natural history of AAAs, the structural, mechanical, and histological characteristics of ILTs have been studied with great interest over the past decade. Given that the ILT is evolving and changing its composition during AAA progression, attention has been paid to exploring the chemomechanical effects of ILT on the underlying wall properties. Various biomechanical and chemomechanical data, and related models have provided advanced insights into AAA pathogenesis which have served as a basis for clinical diagnosis. The goal of this review is to describe and summarize recent advances in the research of ILT found in the aorta in terms of structure, mechanics, and histology on a patient-specific basis. We point to some possible future studies which hopefully stimulate multidisciplinary research to address open problems.

The high opening of the right bronchial artery with a non-typical course.

PubMed

Maciejewski, R; Madej, B; Anasiewicz, A

1995-01-01

Authors describing the bronchial vessels agree to the fact that they are characterised by a great variability in regard to their number and the place where they leave aorta (1, 2, 6). The characteristic feature of the right bronchial artery is that it often forms common trunks with other vessels (mainly with the first right aortic intercostal branch or with one of the upper oesophageal arteries). It can also have a common let-out trunk with the left upper bronchial artery (4). Bearing in mind that the operations on trachea and bronchi are difficult, and that it is very important to maintain the blood supply of the walls in the operated organs we have decided to publish our observations. They refer to a case, not described before, in which the right bronchial artery left the aortic arch in a high position making the vascular supply to the front lower half of the trachea and its bifurcation. Then, it went down to the membranous part of the right bronchus.

Protection against atherogenesis with the polymer drag-reducing agent Separan AP-30.

PubMed

Faruqui, F I; Otten, M D; Polimeni, P I

1987-03-01

The inhibitory effect of Separan AP-30, an anionic polyacrylamide, on atherosclerotic plaque formation in aortas of rabbits on a high (2%) cholesterol diet was tested over a period extending from 37 to 170 days. Atherogenesis was quantified morphometrically by application of a computer-assisted image analysis of histologic cross sections of the aorta. The area of vessel wall-atheroma interface, fraction of lumen occluded, and other indexes of atherogenesis were measured in each of 26 segments of aorta excised from the animals, half of which were administered injections (intravenous) of Separan three times a week. Regression analysis of the morphometric data indicates that the polyelectrolyte exerts a powerful antiatherogenic effect in all regions of the aorta, inhibiting the formation of plaque mass to less than half in the aortic arch and about one-fifth in the descending aorta as compared with the aortic plaque masses in untreated rabbits. Results are compatible with the suggestion that a novel hemodynamic principle in vivo, polymer drag reduction, might be effectively applied against atherosclerosis.

The effect of inlet boundary conditions in image-based CFD modeling of aortic flow

NASA Astrophysics Data System (ADS)

Madhavan, Sudharsan; Kemmerling, Erica Cherry

2016-11-01

CFD of cardiovascular flow is a growing and useful field, but simulations are subject to a number of sources of uncertainty which must be quantified. Our work focuses on the uncertainty introduced by the selection of inlet boundary conditions in an image-based, patient-specific model of the aorta. Specifically, we examined the differences between plug flow, fully developed parabolic flow, linear shear flows, skewed parabolic flow profiles, and Womersley flow. Only the shape of the inlet velocity profile was varied-all other parameters were held constant between simulations, including the physiologically realistic inlet flow rate waveform and outlet flow resistance. We found that flow solutions with different inlet conditions did not exhibit significant differences beyond 1 . 75 inlet diameters from the aortic root. Time averaged wall shear stress (TAWSS) was also calculated. The linear shear velocity boundary condition solution exhibited the highest spatially averaged TAWSS, about 2 . 5 % higher than the fully developed parabolic velocity boundary condition, which had the lowest spatially averaged TAWSS.

Management of Endovascular Aortic Aneurysm Complications via Retrograde Catheterization Through the Distal Stent-Graft Landing Zone.

PubMed

Zhang, Xicheng; Sun, Yuan; Chen, Zhaolei; Jing, Yuanhu; Xu, Miao

2017-08-01

A retrograde technique through the gap between the distal stent landing zone and the iliac artery wall has been applied to treat type II endoleak after endovascular aortic aneurysm repair (EVAR). In this study, we tried to investigate its efficacy in the management of type III endoleak and intraoperative accidental events. We reported 2 complications of EVAR that were difficult to treat with conventional methods. One patient had a sustained type III endoleak after EVAR, and the right renal artery was accidentally sealed by a graft stent in the other patient during the operation. Both complications were managed by the retrograde technique from the distal stent landing zone. In the first case, the endoleak was easily embolized by the retrograde catheterization technique, and in the second case, a stent was implanted in the right renal artery using the retrograde technique to restore blood flow. In some EVAR cases, the technique of retrograde catheterization through the distal stent-graft landing zone is feasible, safe, and easy to perform.

Two-dimensional aortographic coronary angiography with synchrotron radiation at aortic regurgitation state

NASA Astrophysics Data System (ADS)

Takeda, Tohoru; Umetani, Keiji; Doi, Toshiki; Itai, Yuji; Yu, Quanwen; Akatsuka, Takao

1999-10-01

At aortic regurgitation state, 2D synchrotron radiation (SR) coronary arteriography (CAG) with aortographic contrast injection was examined theoretically and animal experiments were performed to confirm its diagnostic ability. This system consisted of a silicon monocrystal, fluorescent plate, avalanche-type pickup tube camera, and image acquisition system. The experiment was performed at synchrotron sources in the Photon Factory of Tsukuba. The x- ray energy was adjusted to just above the iodine K-edge. Theoretical calculation described that the coronary arteries overlapping on left ventricle could not be demonstrated well with a high signal-to-noise ratio by using the aortographic CAG with SR. The canine coronary arteries without overlap over the left ventricle were demonstrated clearly, however, the image quality appear to be reduced. The coronary artery overlapping over left ventricle could not be demonstrated well, however the transient reduction of left ventricular wall motion was revealed by transient stenotic procedure of left anterior descending coronary artery.

Losartan Attenuates Degradation of Aorta and Lung Tissue Micromechanics in a Mouse Model of Severe Marfan Syndrome.

PubMed

Lee, Jia-Jye; Galatioto, Josephine; Rao, Satish; Ramirez, Francesco; Costa, Kevin D

2016-10-01

Marfan syndrome (MFS) is an autosomal dominant disease of the connective tissue due to mutations in the fibrillin-1 gene (FBN1). This study aimed at characterizing microelastic properties of the ascending aortic wall and lung parenchyma tissues from wild type (WT) and age-matched Fbn1 hypomorphic mice (Fbn1(mgR/mgR) mice) to identify tissue-specific biomechanical effects of aging and disease in MFS. Atomic force microscopy was used to indent lung parenchyma and aortic wall tissues, using Hybrid Eshelby Decomposition analysis to extract layer-specific properties of the intima and media. The intima stiffened with age and was not different between WT and Fbn1(mgR/mgR) tissues, whereas the media layer of MFS aortas showed progressive structural and mechanical degradation with a modulus that was 50% softer than WT by 3.5 months of age. Similarly, MFS mice displayed progressive structural and mechanical deterioration of lung tissue, which was over 85% softer than WT by 3.5 months of age. Chronic treatment with the angiotensin type I receptor antagonist, losartan, attenuated the aorta and lung tissue degradation, resulting in structural and mechanical properties not significantly different from age-matched WT controls. By revealing micromechanical softening of elastin-rich aorta and lung tissues with disease progression in fibrillin-1 deficient mice, our findings support the use of losartan as a prophylactic treatment that may abrogate the life-threatening symptoms of MFS.

Chronic clenbuterol administration negatively alters cardiac function.

PubMed

Sleeper, Margaret M; Kearns, Charles F; McKeever, Kenneth H

2002-04-01

Chronic administration of pharmacological levels of beta2-agonists have been shown to have toxic effects on the heart; however, no data exist on cardiac function after chronic clenbuterol administration. The purpose of this study was to examine the effect of therapeutic levels of clenbuterol on cardiac performance. Twenty unfit Standardbred mares were divided into four experimental groups: clenbuterol (2.4 microg.kg(-1) twice daily 5 d.wk(-1)) plus exercise (20 min at 50% .VO(2max)) (CLENEX; N = 6), clenbuterol (CLEN; N = 6), exercise (EX; N = 4), and control (CON; N = 4). M-mode and two-dimensional echocardiography (2.5-MHz sector scanner transducer) were used to measure cardiac size and function before and immediately after an incremental exercise test, before and after 8 wk of drug and/or exercise treatments. After treatment, CLENEX and CLEN demonstrated significantly higher left ventricular internal dimension (LVD) at end diastole (+23.7 +/- 4.8%; +25.6 +/- 4.1%), LVD at end systole (+29.2 +/- 8.7%; +40.1 +/- 7.9%), interventricular septal wall thickness (IVS) at end diastole (+28.9 +/- 11.0%; +30.7 +/- 7.0%), IVS at end systole (+29.2 +/- 8.7%; +40.1 +/- 7.9%), and left ventricular posterior wall systolic thickness (+43.1 +/- 14.%; +45.8 +/- 14.1%). CLENEX and CLEN had significantly increased aortic root dimensions (+29.9 +/- 6.1%; +24.0 +/- 1.7%), suggesting increased risk of aortic rupture. Taken together, these data indicate that chronic clenbuterol administration may negatively alter cardiac function.

Tributyltin chloride disrupts aortic vascular reactivity and increases reactive oxygen species production in female rats.

PubMed

Ximenes, Carolina Falcão; Rodrigues, Samya Mere Lima; Podratz, Priscila Lang; Merlo, Eduardo; de Araújo, Julia Fernandez Puñal; Rodrigues, Lívia Carla Melo; Coitinho, Juliana Barbosa; Vassallo, Dalton Valentim; Graceli, Jones Bernardes; Stefanon, Ivanita

2017-11-01

Organotin compounds, such as tributyltin (TBT), are environment contaminants that induce bioaccumulation and have potential toxic effects on marine species and mammals. TBT have been banned by the International Maritime Organization in 2003. However, the assessment of butyltin and metal contents in marine sediments has demonstrated high residual levels of TBT in some cases exceeding 7000 ng Sn g -1 . The acceptable daily intake (ADI) level for TBT established by the World Health Organization is 0.5 μg/kg bw/day is based on genotoxicity, reproduction, teratogenicity, immunotoxicity, and mainly neurotoxicity. However, their effect on the cardiovascular system is not well understood. In this study, female rats were exposed to 0.5 μg/kg/day of TBT for 15 days with the goal of understanding the effect of TBT on vascular function. Female Wistar rats were treated daily by gavage and divided into control (n = 10) and TBT (n = 10) groups. The aortic rings were incubated with phenylephrine in both the presence and absence of endothelium. The phenylephrine concentration-response curves were generated by exposing endothelium-intact samples to N G -nitro-L-arginine methyl ester (L-NAME), apocynin, superoxide dismutase (SOD), catalase, tiron, and allopurinol. Acetylcholine (ACh) and sodium nitroprusside (SNP) were used to evaluate the relaxation response. Exposure to TBT reduced serum 17β-estradiol E 2 levels and increased vascular reactivity. After incubation with L-NAME, the vascular reactivity to phenylephrine was significantly higher. Apocynin, SOD, catalase, and tiron decreased the vascular reactivity to phenylephrine to a significantly greater extent in TBT-treated rats than in the control rat. The relaxation induced by ACh and SNP was significantly reduced in TBT rats. Exposure to TBT induced aortic wall atrophy and increased superoxide anion production and collagen deposition. These results provide evidence that exposing rats to the current ADI for TBT (0.5 μg/kg) for 15 days induced vascular dysfunction due to oxidative stress and morphological damage and should be considered an important cardiovascular risk factor.

Plasma complement and vascular complement deposition in patients with coronary artery disease with and without inflammatory rheumatic diseases

PubMed Central

2017-01-01

Purpose Inflammatory rheumatic diseases (IRD) are associated with accelerated coronary artery disease (CAD), which may result from both systemic and vascular wall inflammation. There are indications that complement may be involved in the pathogenesis of CAD in Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA). This study aimed to evaluate the associations between circulating complement and complement activation products with mononuclear cell infiltrates (MCI, surrogate marker of vascular inflammation) in the aortic media and adventitia in IRDCAD and non-IRDCAD patients undergoing coronary artery bypass grafting (CABG). Furthermore, we compared complement activation product deposition patterns in rare aorta adventitial and medial biopsies from SLE, RA and non-IRD patients. Methods We examined plasma C3 (p-C3) and terminal complement complexes (p-TCC) in 28 IRDCAD (SLE = 3; RA = 25), 52 non-IRDCAD patients, and 32 IRDNo CAD (RA = 32) from the Feiring Heart Biopsy Study. Aortic biopsies taken from the CAD only patients during CABG were previously evaluated for adventitial MCIs. The rare aortic biopsies from 3 SLE, 3 RA and 3 non-IRDCAD were assessed for the presence of C3 and C3d using immunohistochemistry. Results IRDCAD patients had higher p-TCC than non-IRDCAD or IRDNo CAD patients (p<0.0001), but a similar p-C3 level (p = 0.42). Circulating C3 was associated with IRD duration (ρ, p-value: 0.46, 0.03). In multiple logistic regression analysis, IRD remained significantly related to the presence and size of MCI (p<0.05). C3 was present in all tissue samples. C3d was detected in the media of all patients and only in the adventitia of IRD patients (diffuse in all SLE and focal in one RA). Conclusion The independent association of IRD status with MCI and the observed C3d deposition supports the unique relationship between rheumatic disease, and, in particular, SLE with the complement system. Exaggerated systemic and vascular complement activation may accelerate CVD, serve as a CVD biomarker, and represent a target for new therapies. PMID:28362874

Sensitive enhancement of vessel wall imaging with an endoesophageal Wireless Amplified NMR Detector (WAND).

PubMed

Zeng, Xianchun; Barbic, Mladen; Chen, Liangliang; Qian, Chunqi

2017-11-01

To improve the imaging quality of vessel walls with an endoesophageal Wireless Amplified NMR Detector (WAND). A cylindrically shaped double-frequency resonator has been constructed with a single metal wire that is self-connected by a pair of nonlinear capacitors. The double-frequency resonator can convert wirelessly provided pumping power into amplified MR signals. This compact design makes the detector easily insertable into a rodent esophagus. The detector has good longitudinal and axial symmetry. Compared to an external surface coil, the WAND can enhance detection sensitivity by at least 5 times, even when the distance separation between the region of interest and the detector's cylindrical surface is twice the detector's own radius. Such detection capability enables us to observe vessel walls near the aortic arch and carotid bifurcation with elevated sensitivity. A cylindrical MRI detector integrated with a wireless-powered amplifier has been developed as an endoesophageal detector to enhance detection sensitivity of vessel walls. This detector can greatly improve the imaging quality for vessel regions that are susceptible to atherosclerotic lesions. Magn Reson Med 78:2048-2054, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Fourier transform infrared spectroscopy to quantify collagen and elastin in an in vitro model of extracellular matrix degradation in aorta.

PubMed

Cheheltani, Rabee; McGoverin, Cushla M; Rao, Jayashree; Vorp, David A; Kiani, Mohammad F; Pleshko, Nancy

2014-06-21

Extracellular matrix (ECM) is a key component and regulator of many biological tissues including aorta. Several aortic pathologies are associated with significant changes in the composition of the matrix, especially in the content, quality and type of aortic structural proteins, collagen and elastin. The purpose of this study was to develop an infrared spectroscopic methodology that is comparable to biochemical assays to quantify collagen and elastin in aorta. Enzymatically degraded porcine aorta samples were used as a model of ECM degradation in abdominal aortic aneurysm (AAA). After enzymatic treatment, Fourier transform infrared (FTIR) spectra of the aortic tissue were acquired by an infrared fiber optic probe (IFOP) and FTIR imaging spectroscopy (FT-IRIS). Collagen and elastin content were quantified biochemically and partial least squares (PLS) models were developed to predict collagen and elastin content in aorta based on FTIR spectra. PLS models developed from FT-IRIS spectra were able to predict elastin and collagen content of the samples with strong correlations (RMSE of validation = 8.4% and 11.1% of the range respectively), and IFOP spectra were successfully used to predict elastin content (RMSE = 11.3% of the range). The PLS regression coefficients from the FT-IRIS models were used to map collagen and elastin in tissue sections of degraded porcine aortic tissue as well as a human AAA biopsy tissue, creating a similar map of each component compared to histology. These results support further application of FTIR spectroscopic techniques for evaluation of AAA tissues.

Fourier Transform Infrared Spectroscopy to Quantify Collagen and Elastin in an In Vitro Model of Extracellular Matrix Degradation in Aorta

PubMed Central

Cheheltani, Rabee; McGoverin, Cushla M.; Rao, Jayashree; Vorp, David A.; Kiani, Mohammad F.; Pleshko, N.

2014-01-01

Extracellular matrix (ECM) is a key component and regulator of many biological tissues including aorta. Several aortic pathologies are associated with significant changes in the composition of the matrix, especially in the content, quality and type of aortic structural proteins, collagen and elastin. The purpose of this study was to develop an infrared spectroscopic methodology that is comparable to biochemical assays to quantify collagen and elastin in aorta. Enzymatically degraded porcine aorta samples were used as a model of ECM degradation in abdominal aortic aneurysm (AAA). After enzymatic treatment, Fourier transform infrared (FTIR) spectra of the aortic tissue were acquired by an infrared fiber optic probe (IFOP) and FTIR imaging spectroscopy (FT-IRIS). Collagen and elastin content were quantified biochemically and partial least squares (PLS) models were developed to predict collagen and elastin content in aorta based on FTIR spectra. PLS models developed from FT-IRIS spectra were able to predict elastin and collagen content of the samples with strong correlations (RMSE of validation = 8.4% and 11.1% of the range respectively), and IFOP spectra were successfully used to predict elastin content (RMSE = 11.3% of the range). The PLS regression coefficients from the FT-IRIS models were used to map collagen and elastin in tissue sections of degraded porcine aortic tissue as well as a human AAA biopsy tissue, creating a similar map of each component compared to histology. These results support further application of FTIR spectroscopic techniques for evaluation of AAA tissues. PMID:24761431

Elimination of Trans-coarctation Pressure Gradients Has No Impact on Left Ventricular Function or Aortic Shear Stress Post Intervention in Patients with Mild Coarctation

PubMed Central

Keshavarz-Motamed, Zahra; Nezami, Farhad Rikhtegar; Partida, Ramon A.; Nakamura, Kenta; Staziaki, Pedro Vinícius; Ben-Assa, Eyal; Ghoshhajra, Brian; Bhatt, Ami B.; Edelman, Elazer R.

2017-01-01

OBJECTIVES To investigate the impact of transcatheter intervention on left ventricular (LV) function and aortic hemodynamics in patients with mild coarctation of the aorta (COA). BACKGROUND The optimal method and timing of transcatheter intervention for COA remains unclear, especially when the severity of COA is mild (peak-to-peak trans-coarctation pressure gradient, PKdP < 20 mmHg). Debate rages regarding the risk/benefit ratio of intervention vs. long-term effects of persistent minimal gradient in this heterogeneous population with differing blood pressures, ventricular function and peripheral perfusion. METHODS We developed a unique computational fluid dynamics and lumped parameter modeling framework based on patient-specific hemodynamic input parameters and validated it against patient-specific clinical outcomes (pre- and post-intervention). We used clinically measured hemodynamic metrics and imaging of the aorta and the LV in thirty-four patients with mild COA to make these correlations. RESULTS Despite dramatic reduction in trans-coarctation pressure gradient (catheter and Doppler echocardiography pressure gradients reduced 75% and 47.3%,), there was only modest effect on aortic flow and no significant impact on aortic shear stress (maximum time-averaged wall shear stress in descending aorta was reduced 5.1%). In no patient did transcatheter intervention improve LV function (e.g., stroke work and normalized stroke work were reduced by only 4.48% and 3.9%). CONCLUSIONS Transcatheter intervention which successfully relieves mild COA pressure gradients does not translate to decrease myocardial strain. The effects of intervention were determined to the greatest degree by ventricular-vascular coupling hemodynamics, and provide a novel valuable mechanism to evaluate patients with COA which may influence clinical practice. PMID:27659574

A study of quantification of aortic compliance in mice using radial acquisition phase contrast MRI

NASA Astrophysics Data System (ADS)

Zhao, Xuandong

Spatiotemporal changes in blood flow velocity measured using Phase contrast Magnetic Resonance Imaging (MRI) can be used to quantify Pulse Wave Velocity (PWV) and Wall Shear Stress (WSS), well known indices of vessel compliance. A study was conducted to measure the PWV in the aortic arch in young healthy children using conventional phase contrast MRI and a post processing algorithm that automatically track the peak velocity in phase contrast images. It is shown that the PWV calculated using peak velocity-time data has less variability compared to that using mean velocity and flow. Conventional MR data acquisition techniques lack both the spatial and temporal resolution needed to accurately calculate PWV and WSS in in vivo studies using transgenic animal models of arterial diseases. Radial k-space acquisition can improve both spatial and temporal resolution. A major part of this thesis was devoted to developing technology for Radial Phase Contrast Magnetic Resonance (RPCMR) cine imaging on a 7 Tesla Animal scanner. A pulse sequence with asymmetric radial k-space acquisition was designed and implemented. Software developed to reconstruct the RPCMR images include gridding, density compensation and centering of k-Space that corrects the image ghosting introduced by hardware response time. Image processing software was developed to automatically segment the vessel lumen and correct for phase offset due to eddy currents. Finally, in vivo and ex vivo aortic compliance measurements were conducted in a well-established mouse model for atherosclerosis: Apolipoprotein E-knockout (ApoE-KO). Using RPCMR technique, a significantly higher PWV value as well as a higher average WSS was detected among 9 months old ApoE-KO mice compare to in wild type mice. A follow up ex-vivo test of tissue elasticity confirmed the impaired distensibility of aortic arteries among ApoE-KO mice.

Circulating cadmium concentration and risk of aortic aneurysms: A nested case-control study within the Malmö Diet and Cancer cohort.

PubMed

Fagerberg, Björn; Borné, Yan; Sallsten, Gerd; Smith, J Gustav; Acosta, Stefan; Persson, Margaretha; Melander, Olle; Forsgard, Niklas; Gottsäter, Anders; Hedblad, Bo; Barregard, Lars; Engström, Gunnar

2017-06-01

Diet and smoking expose the general population to cadmium (Cd), which is a toxic metal that accumulates in the arterial wall. In experimental studies, Cd causes reductions in proliferation of smooth muscle cells and cellular synthesis of procollagen. The aim of this study was to examine whether blood Cd levels, a valid measure of Cd exposure, are associated with increased risk of abdominal aortic aneurysm (AAA). All middle-aged men and women enrolled in the Malmö Diet and Cancer study (n = 30 447) were followed from the baseline examination in 1991-1996 through 2009. A total of 297 cases with AAA and two randomly selected control subjects for each case, matched for age and sex, were included. Blood Cd was analysed by inductively coupled plasma mass spectrometry. Diagnoses of AAA, thoracic aortic aneurysm and aortic dissection were obtained from registers. Increased blood Cd was associated with increased risk of incident AAA after adjustment for smoking and other established risk factors for AAA. The highest tertile of blood Cd concentrations had a rate ratio of 2.5 (95% confidence interval 1.3, 5.0) for incident AAA. Concentration of blood Cd (log transformed) was not associated with AAA in never-smokers (n = 24). Blood Cd levels corresponding to the upper tertile of the distribution in the age- and sex-matched control group were associated with a 2.5-fold increase in rate ratio for incident AAA. This relationship was not found in the small group of never-smokers. Copyright © 2017. Published by Elsevier B.V.

Prevalence and Impact of Coexistent Bicuspid Aortic Valve in Hypertrophic Cardiomyopathy.

PubMed

Padang, Ratnasari; Gersh, Bernard J; Ommen, Steve R; Geske, Jeffrey B

2018-01-01

The association between bicuspid aortic valve (BAV) and hypertrophic cardiomyopathy (HCM) has been reported but its true prevalence is unknown. This study investigated the prevalence and clinical impact of coexistent BAV in a large referral HCM population. Retrospective analysis of 3765 echocardiograms between 2004 and 2014 in 2640 consecutive patients with HCM was performed to assess for BAV. Patients with coexistent conditions were studied. Twenty-three patients (0.9%) were identified with coexisting BAV and HCM. Mean age was 52±16years, 18 males (78%), 16 with NYHA functional class I/II at initial evaluation (70%). A family history of HCM was present in five patients (22%); none had a family history of BAV or aortopathy. Maximal left ventricular wall thickness was 24±6mm; the majority had either reverse curve or sigmoid septal morphology. Moderate or greater aortic valve dysfunction was present in seven patients (30%), BAV-related aortopathy in 18 patients (78%) and dynamic left ventricular outflow tract (LVOT) obstruction in nine patients (39%). Three patients had combined LVOT obstruction and aortic stenosis. Median time from diagnosis of BAV or HCM to last follow-up was 11±12.5years. At last follow-up, 22% had undergone BAV-related surgeries, 30% had septal reduction therapy (SRT), and 17% had combined SRT and BAV-related surgeries. Overall survival was 95% at 10 years. This study reported a 0.9% prevalence of BAV among HCM population, similar to the general population. Aortopathy and LVOT obstruction were common, necessitating cardiac interventions in over one-third of cases. Long-term survival appeared favourable. 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.

SMYD2 promoter DNA methylation is associated with abdominal aortic aneurysm (AAA) and SMYD2 expression in vascular smooth muscle cells.

PubMed

Toghill, Bradley J; Saratzis, Athanasios; Freeman, Peter J; Sylvius, Nicolas; Bown, Matthew J

2018-01-01

Abdominal aortic aneurysm (AAA) is a deadly cardiovascular disease characterised by the gradual, irreversible dilation of the abdominal aorta. AAA is a complex genetic disease but little is known about the role of epigenetics. Our objective was to determine if global DNA methylation and CpG-specific methylation at known AAA risk loci is associated with AAA, and the functional effects of methylation changes. We assessed global methylation in peripheral blood mononuclear cell DNA from 92 individuals with AAA and 93 controls using enzyme-linked immunosorbent assays, identifying hyper-methylation in those with large AAA and a positive linear association with AAA diameter ( P  < 0.0001, R 2  = 0.3175).We then determined CpG methylation status of regulatory regions in genes located at AAA risk loci identified in genome-wide association studies, using bisulphite next-generation sequencing (NGS) in vascular smooth muscle cells (VSMCs) taken from aortic tissues of 44 individuals (24 AAAs and 20 controls). In IL6R , 2 CpGs were hyper-methylated ( P  = 0.0145); in ERG , 13 CpGs were hyper-methylated ( P  = 0.0005); in SERPINB9 , 6 CpGs were hypo-methylated ( P  = 0.0037) and 1 CpG was hyper-methylated ( P  = 0.0098); and in SMYD2 , 4 CpGs were hypo-methylated ( P  = 0.0012).RT-qPCR was performed for each differentially methylated gene on mRNA from the same VSMCs and compared with methylation. This analysis revealed downregulation of SMYD2 and SERPINB9 in AAA, and a direct linear relationship between SMYD2 promoter methylation and SMYD2 expression ( P  = 0.038). Furthermore, downregulation of SMYD2 at the site of aneurysm in the aortic wall was further corroborated in 6 of the same samples used for methylation and gene expression analysis with immunohistochemistry. This study is the first to assess DNA methylation in VSMCs from individuals with AAA using NGS, and provides further evidence there is an epigenetic basis to AAA. Our study shows that methylation status of the SMYD2 promoter may be linked with decreased SMYD2 expression in disease pathobiology. In support of our work, downregulated SMYD2 has previously been associated with adverse cardiovascular physiology and inflammation, which are both hallmarks of AAA. The identification of such adverse epigenetic modifications could potentially contribute towards the development of epigenetic treatment strategies in the future.

Endovascular Repair of Thoracoabdominal and Arch Aneurysms in Patients with Connective Tissue Disease Using Branched and Fenestrated Devices.

PubMed

Clough, Rachel E; Martin-Gonzalez, Teresa; Van Calster, Katrien; Hertault, Adrien; Spear, Rafaëlle; Azzaoui, Richard; Sobocinski, Jonathan; Haulon, Stéphan

2017-10-01

Prophylactic open surgery is the standard practice in patients with connective tissue and thoracoabdominal aortic aneurysm (TAAA) and aortic arch disease. Branched and fenestrated devices offer a less invasive alternative but there are concerns regarding the durability of the repair and the effect of the stent graft on the fragile aortic wall. The aim of this study is to evaluate mid-term outcomes of fenestrated and/or branched endografting in patients with connective tissue disease. All patients with connective tissue disease who underwent TAAA or arch aneurysm repair using a fenestrated and/or branched endograft in a single, high-volume center between 2004 and 2015 were included. Ruptured aneurysms and acute aortic dissections were excluded from this study, but not chronic aortic dissections. In total, 427 (403 pararenal and TAAAs, and 24 arch aneurysms) endovascular interventions were performed during the study period. Of these, 17 patients (4%) (16 TAAAs, 1 arch) had connective tissue disease. All patients were classified as unfit for open repair. The mean age was 51 ± 8 years. Thirteen patients with TAAA were treated with a fenestrated, 1 with a branched, and 2 with a combined fenestrated/branch device. A double inner branch device was used to treat the arch aneurysm. The technical success rate was 100% with no incidence of early mortality, spinal cord ischemia, stroke, or further dissection. Postoperative deterioration in renal function was seen in 3 patients (18.8%) and no hemodialysis was required. The mean follow-up was 3.4 years (0.3-7.4). Aneurysm sac shrinkage was seen in 35% of patients (6/17) and the sac diameter remained stable in 65% of patients (11/17). No sac or sealing zone enlargement was observed in any of the patients and there were no conversions to open repair. Reintervention was required in 1 patient at 2 years for bilateral renal artery occlusion (successful fibrinolysis). One type II endoleak (lumbar) is under surveillance and 1 type III (left renal stent) sealed spontaneously. One patient died at 2 years after the procedure from nonaortic causes (endocarditis). The favorable mid-term outcomes in this series that demonstrate fenestrated and/or branched endografting should be considered in patients with connective tissue and TAAA and aortic arch disease, which are considered unfit for open surgery. All patients require close lifetime surveillance at a center specializing in aortic surgery, with sufficient experience in both open and endovascular aortic surgery, so that if endovascular treatment failure occurs it can be recognized early and further treatment offered. Copyright © 2017 Elsevier Inc. All rights reserved.

Sulforaphane attenuates the development of atherosclerosis and improves endothelial dysfunction in hypercholesterolemic rabbits.

PubMed

Shehatou, George S G; Suddek, Ghada M

2016-02-01

The aim of the present work was to explore possible protective effects of sulforaphane (SFN) against atherosclerosis development and endothelial dysfunction in hypercholesterolemic rabbits. Rabbits were assigned to three groups of five: group I fed normal chow diet for four weeks, group II fed 1% high cholesterol diet (HCD) and group III fed HCD + SFN (0.25 mg/kg/day). Blood samples were collected for measurement of serum triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), lactate dehydrogenase (LDH) and C-reactive protein (CRP). Aortic malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and total nitrite/nitrate (NOx) were measured. Vascular reactivity and intima/media (I/M) ratio were analyzed. Nuclear factor-kappa B (NF-κB) activation in aortic endothelial cells was identified immunohistochemically. HCD induced significant increases in serum TGs, TC, LDL-C, LDH, and CRP, and aortic MDA and SOD. Moreover, HCD caused significant reductions in serum HDL-C, aortic GSH and NOx. SFN administration significantly decreased HCD-induced elevations in serum TC, LDL-C, CRP, and LDH. while significantly increased HDL-C and GSH levels and normalized aortic SOD and NOx. Additionally, SFN significantly improved rabbit aortic endothelium-dependent relaxation to acetylcholine. Moreover, SFN significantly reduced the elevation in I/M ratio. This effect was confirmed by aortic histopathologic examination. The expression of NF-κB in aortic tissue showed a marked reduction upon treatment with SFN. In conclusion, this study reveals that SFN has the ability to ameliorate HCD-induced atherosclerotic lesions progression and vascular dysfunction, possibly via its lipid-lowering and antioxidant effects and suppression of NF-κB-mediated inflammation. © 2016 by the Society for Experimental Biology and Medicine.

Sulforaphane attenuates the development of atherosclerosis and improves endothelial dysfunction in hypercholesterolemic rabbits

PubMed Central

Suddek, Ghada M

2016-01-01

The aim of the present work was to explore possible protective effects of sulforaphane (SFN) against atherosclerosis development and endothelial dysfunction in hypercholesterolemic rabbits. Rabbits were assigned to three groups of five: group I fed normal chow diet for four weeks, group II fed 1% high cholesterol diet (HCD) and group III fed HCD + SFN (0.25 mg/kg/day). Blood samples were collected for measurement of serum triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), lactate dehydrogenase (LDH) and C-reactive protein (CRP). Aortic malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and total nitrite/nitrate (NOx) were measured. Vascular reactivity and intima/media (I/M) ratio were analyzed. Nuclear factor-kappa B (NF-κB) activation in aortic endothelial cells was identified immunohistochemically. HCD induced significant increases in serum TGs, TC, LDL-C, LDH, and CRP, and aortic MDA and SOD. Moreover, HCD caused significant reductions in serum HDL-C, aortic GSH and NOx. SFN administration significantly decreased HCD-induced elevations in serum TC, LDL-C, CRP, and LDH. while significantly increased HDL-C and GSH levels and normalized aortic SOD and NOx. Additionally, SFN significantly improved rabbit aortic endothelium-dependent relaxation to acetylcholine. Moreover, SFN significantly reduced the elevation in I/M ratio. This effect was confirmed by aortic histopathologic examination. The expression of NF-κB in aortic tissue showed a marked reduction upon treatment with SFN. In conclusion, this study reveals that SFN has the ability to ameliorate HCD-induced atherosclerotic lesions progression and vascular dysfunction, possibly via its lipid-lowering and antioxidant effects and suppression of NF-κB-mediated inflammation. PMID:26490346

Athletic Cardiac Remodeling in US Professional Basketball Players.

PubMed

Engel, David J; Schwartz, Allan; Homma, Shunichi

2016-04-01

The incidence of sudden cardiac death is higher in US basketball players compared with other athlete groups. However, the recognition of the risk for sudden cardiac death among basketball players is challenging because little is known regarding athletic cardiac remodeling in these athletes or athletes of similarly increased size. To perform a comprehensive cardiac structural analysis of National Basketball Association (NBA) professional athletes. Echocardiographic observational study of NBA players on the active rosters for the 2013-2014 and 2014-2015 seasons was performed from December 16, 2013, to December 12, 2014. The policy of the NBA mandates annual preseason stress echocardiograms for each player. The NBA has sanctioned Columbia University Medical Center to conduct annual health and safety reviews of these echocardiograms. Data were analyzed from January to May 2015. Cardiac variables assessed included left ventricular (LV) size, mass, wall thickness, and hypertrophy patterns and function; left atrial volume; and aortic root diameter. All dimensions were biometrically scaled. Of the 526 athletes included in the study, 406 (77.2%) were African American and 107 (20.3%) were white, with a mean (SD) age of 25.7 (4.3) years. Mean (SD) athlete height was 200.2 (8.8) cm; mean body surface area, 2.38 (0.19) m2. Left ventricular size and mass in NBA athletes were proportional to body size, extending to the uppermost biometrics of the cohort. Left ventricular hypertrophy was present in 144 athletes (27.4%). African American athletes had increased LV wall thickness (unadjusted mean, 11.2 mm; 95% CI, 11.1-11.3 mm) and LV mass (unadjusted mean, 106.3 g/m2; 95% CI, 104.6-108.0 g/m2) compared with LV wall thickness (unadjusted mean, 10.5 mm; 95% CI, 10.3-10.7 mm; P < .001) and LV mass (unadjusted mean, 102.2 g/m2; 95% CI, 99.0-105.4 g/m2; P = .029) in white athletes. The maximal aortic root diameter in the cohort was 42 mm. Aortic root diameters reached a plateau at the uppermost biometric variables. Five athletes (1.0%) had an LV ejection fraction of less than 50%, and all ventricles augmented normally with exercise. This study provides normative cardiac data for a group of athletes with greater anthropometry than any previously studied athlete group and for a group known to have elevated rates of sudden cardiac death. These data can be incorporated into clinical assessments for the primary prevention of cardiac emergencies in basketball players and the athletic community at large.

Re-evaluation of hypoplastic left heart syndrome from a developmental and morphological perspective.

PubMed

Crucean, A; Alqahtani, A; Barron, D J; Brawn, W J; Richardson, R V; O'Sullivan, J; Anderson, R H; Henderson, D J; Chaudhry, B

2017-08-10

Hypoplastic left heart syndrome (HLHS) covers a spectrum of rare congenital anomalies characterised by a non-apex forming left ventricle and stenosis/atresia of the mitral and aortic valves. Despite many studies, the causes of HLHS remain unclear and there are conflicting views regarding the role of flow, valvar or myocardial abnormalities in its pathogenesis, all of which were proposed prior to the description of the second heart field. Our aim was to re-evaluate the patterns of malformation in HLHS in relation to recognised cardiac progenitor populations, with a view to providing aetiologically useful sub-groupings for genomic studies. We examined 78 hearts previously classified as HLHS, with subtypes based on valve patency, and re-categorised them based on their objective ventricular phenotype. Three distinct subgroups could be identified: slit-like left ventricle (24%); miniaturised left ventricle (6%); and thickened left ventricle with endocardial fibroelastosis (EFE; 70%). Slit-like ventricles were always found in combination with aortic atresia and mitral atresia. Miniaturised left ventricles all had normally formed, though smaller aortic and mitral valves. The remaining group were found to have a range of aortic valve malformations associated with thickened left ventricular walls despite being described as either atresia or stenosis. The degree of myocardial thickening was not correlated to the degree of valvar stenosis. Lineage tracing in mice to investigate the progenitor populations that form the parts of the heart disrupted by HLHS showed that whereas Nkx2-5-Cre labelled myocardial and endothelial cells within the left and right ventricles, Mef2c-AHF-Cre, which labels second heart field-derived cells only, was largely restricted to the endocardium and myocardium of the right ventricle. However, like Nkx2-5-Cre, Mef2c-AHF-Cre lineage cells made a significant contribution to the aortic and mitral valves. In contrast, Wnt1-Cre made a major contribution only to the aortic valve. This suggests that discrete cardiac progenitors might be responsible for the patterns of defects observed in the distinct ventricular sub-groups. Only the slit-like ventricle grouping was found to map to the current nomenclature: the combination of mitral atresia with aortic atresia. It appears that slit-like and miniature ventricles also form discrete sub-groups. Thus, reclassification of HLHS into subgroups based on ventricular phenotype, might be useful in genetic and developmental studies in investigating the aetiology of this severe malformation syndrome.