Vascular Response of Triiodothyronine on Isolated Aortic Rings: Contribution of Redox Mechanisms. / Resposta Vascular da Triiodotironina sobre Anéis de Aortas Isoladas: Contribuição de Mecanismos Redox.

BACKGROUND: Vascular dysfunction constitutes the etiology of many diseases, such as myocardial infarction and hypertension, with the disruption of redox homeostasis playing a role in the imbalance of the vasomotor control mechanism. Our group previously has shown that thyroid hormones exert protective effects on the aortic tissue of infarcted rats by improving angiogenesis signaling. OBJECTIVE: Investigate the role of triiodothyronine (T3) on vascular response, exploring its effects on isolated aortas and whether there is an involvement of vascular redox mechanisms. METHODS: Isolated aortic rings (intact- and denuded-endothelium) precontracted with phenylephrine were incubated with T3 (10-8, 10-7, 10-6, 10-5, and 10-4 M), and tension was recorded using a force-displacement transducer coupled with an acquisition system. To assess the involvement of oxidative stress, aortic rings were preincubated with T3 and subsequently submitted to an in vitro reactive oxygen species (ROS) generation system. The level of significance adopted in the statistical analysis was 5%. RESULTS: T3 (10-4 M) promoted vasorelaxation of phenylephrine precontracted aortic rings in both intact- and denuded-endothelium conditions. Aortic rings preincubated in the presence of T3 (10-4 M) also showed decreased vasoconstriction elicited by phenylephrine (1 µM) in intact-endothelium preparations. Moreover, T3 (10-4 M) vasorelaxation effect persisted in aortic rings preincubated with NG-nitro-L-arginine methylester (L-NAME, 10 µM), a nonspecific NO synthase (NOS) inhibitor. Finally, T3 (10-4 M) exhibited, in vitro, an antioxidant role by reducing NADPH oxidase activity and increasing SOD activity in the aorta's homogenates. CONCLUSION: T3 exerts dependent- and independent-endothelium vasodilation effects, which may be related to its role in maintaining redox homeostasis.

FUNDAMENTO: A disfunção vascular constitui a etiologia de diversas doenças, incluindo infarto do miocárdio e hipertensão, diante da ruptura da homeostase oxi-redutiva ("redox"), desempenhando um papel no desequilíbrio do mecanismo de controle vasomotor. Nosso grupo demonstrou anteriormente que os hormônios tireoidianos melhoram a sinalização da angiogênese, exercendo efeitos protetores sobre o tecido aórtico de ratos infartados. OBJETIVOS: Investigar o papel da triiodotironina (T3) na resposta vascular, explorando seus efeitos em aortas isoladas e a presença de mecanismos redox vasculares. MÉTODOS: Anéis aórticos isolados (endotélio intacto e desnudado) pré-contraídos com fenilefrina foram incubados com T3 (10-8, 10-7, 10-6, 10-5 e 10-4 M) e a tensão foi registrada usando um transdutor de deslocamento de força acoplado a um sistema de coleta. Para avaliar o envolvimento do estresse oxidativo, os anéis aórticos foram pré-incubados com T3 e posteriormente submetidos a um sistema de geração de espécies reativas de oxigênio (ROS) in vitro. O nível de significância adotado na análise estatística foi de 5%. RESULTADOS: A T3 (10-4 M) promoveu o vasorrelaxamento dos anéis aórticos pré-contraídos com fenilefrina em endotélio intacto e desnudado. Os anéis aórticos pré-incubados na presença de T3 (10-4 M) também mostraram diminuição da vasoconstrição provocada pela fenilefrina (1 µM) em preparações de endotélio intacto. Além disso, o efeito vasorrelaxante da T3 (10-4 M) persistiu em anéis aórticos pré-incubados com éster metílico de NG-nitro-L-arginina (L-NAME, 10 µM), um inibidor inespecífico da NO sintase (NOS). Por fim, a T3 (10-4 M) exibiu, in vitro, um papel antioxidante ao reduzir a atividade da NADPH oxidase e aumentar a atividade da SOD nos homogenatos aórticos. CONCLUSÃO: A T3 exerce efeitos dependentes e independentes de endotélio, o que pode estar relacionado ao seu papel na manutenção da homeostase redox.

Implicit neural representations for unsupervised super-resolution and denoising of 4D flow MRI.

BACKGROUND AND OBJECTIVE: 4D flow magnetic resonance imaging provides time-resolved blood flow velocity measurements, but suffers from limitations in spatio-temporal resolution and noise. In this study, we investigated the use of sinusoidal representation networks (SIRENs) to improve denoising and super-resolution of velocity fields measured by 4D flow MRI in the thoracic aorta. METHODS: Efficient training of SIRENs in 4D was achieved by sampling voxel coordinates and enforcing the no-slip condition at the vessel wall. A set of synthetic measurements were generated from computational fluid dynamics simulations, reproducing different noise levels. The influence of SIREN architecture was systematically investigated, and the performance of our method was compared to existing approaches for 4D flow denoising and super-resolution. RESULTS: Compared to existing techniques, a SIREN with 300 neurons per layer and 20 layers achieved lower errors (up to 50% lower vector normalized root mean square error, 42% lower magnitude normalized root mean square error, and 15% lower direction error) in velocity and wall shear stress fields. Applied to real 4D flow velocity measurements in a patient-specific aortic aneurysm, our method produced denoised and super-resolved velocity fields while maintaining accurate macroscopic flow measurements. CONCLUSIONS: This study demonstrates the feasibility of using SIRENs for complex blood flow velocity representation from clinical 4D flow, with quick execution and straightforward implementation.

A Systematic Comparison of Normal Structure and Function of the Greater Thoracic Vessels.

The greater thoracic vessels are central to a well-functioning circulatory system and are often targeted in congenital heart surgeries, yet the structure and function of these vessels have not been well studied. Here we use consistent methods to quantify and compare microstructural features and biaxial biomechanical properties of the following six greater thoracic vessels in wild-type mice: ascending thoracic aorta, descending thoracic aorta, right subclavian artery, right pulmonary artery, thoracic inferior vena cava, and superior vena cava. Specifically, we determine volume fractions and orientations of the structurally significant wall constituents (i.e., collagen, elastin, and cell nuclei) using multiphoton imaging, and we quantify vasoactive responses and mechanobiologically relevant mechanical quantities (e.g., stress, stiffness) using computer-controlled biaxial mechanical testing. Similarities and differences across systemic, pulmonary, and venous circulations highlight underlying design principles of the vascular system. Results from this study represent another step towards understanding growth and remodeling of greater thoracic vessels in health, disease, and surgical interventions by providing baseline information essential for developing and validating predictive computational models.

Active and passive mechanical characterization of a human descending thoracic aorta with Klippel-Trenaunay syndrome.

A human aorta from a female donor affected by Klippel-Trenaunay syndrome was retrieved during a surgery for organ donation for transplant. The aorta was preserved in refrigerated Belzer UW organ preservation solution and tested within a few hours for mechanical characterization with and without vascular smooth muscle activation. KCl and Noradrenaline were used as vasoactive agents in bubbled Krebs-Henseleit buffer solution at 37 °C. A quasi-static and a dynamic mechanical characterization of the full wall and the three individual layers were carried out for strips taken in longitudinal and circumferential directions. The full wall in the descending portion of the aorta underwent mechanical tests with and without smooth muscle activation. Results were compared to data obtained from healthy aortas and show a reduced stiffness of the full wall in circumferential direction. Also, a significant reduction of the response to vasoactive agents in circumferential direction was observed, while the longitudinal response was similar to healthy cases.

Impact of the Spatial Velocity Inlet Distribution on the Hemodynamics of the Thoracic Aorta.

The impact of the distribution in space of the inlet velocity in the numerical simulations of the hemodynamics in the thoracic aorta is systematically investigated. A real healthy aorta geometry, for which in-vivo measurements are available, is considered. The distribution is modeled through a truncated cone shape, which is a suitable approximation of the real one downstream of a trileaflet aortic valve during the systolic part of the cardiac cycle. The ratio between the upper and the lower base of the truncated cone and the position of the center of the upper base are selected as uncertain parameters. A stochastic approach is chosen, based on the generalized Polynomial Chaos expansion, to obtain accurate response surfaces of the quantities of interest in the parameter space. The selected parameters influence the velocity distribution in the ascending aorta. Consequently, effects on the wall shear stress are observed, confirming the need to use patient-specific inlet conditions if interested in the hemodynamics of this region. The surface base ratio is globally the most important parameter. Conversely, the impact on the velocity and wall shear stress in the aortic arch and descending aorta is almost negligible.

Impact of wall displacements on the large-scale flow coherence in ascending aorta.

In the context of aortic hemodynamics, uncertainties affecting blood flow simulations hamper their translational potential as supportive technology in clinics. Computational fluid dynamics (CFD) simulations under rigid-walls assumption are largely adopted, even though the aorta contributes markedly to the systemic compliance and is characterized by a complex motion. To account for personalized wall displacements in aortic hemodynamics simulations, the moving-boundary method (MBM) has been recently proposed as a computationally convenient strategy, although its implementation requires dynamic imaging acquisitions not always available in clinics. In this study we aim to clarify the real need for introducing aortic wall displacements in CFD simulations to accurately capture the large-scale flow structures in the healthy human ascending aorta (AAo). To do that, the impact of wall displacements is analyzed using subject-specific models where two CFD simulations are performed imposing (1) rigid walls, and (2) personalized wall displacements adopting a MBM, integrating dynamic CT imaging and a mesh morphing technique based on radial basis functions. The impact of wall displacements on AAo hemodynamics is analyzed in terms of large-scale flow patterns of physiological significance, namely axial blood flow coherence (quantified applying the Complex Networks theory), secondary flows, helical flow and wall shear stress (WSS). From the comparison with rigid-wall simulations, it emerges that wall displacements have a minor impact on the AAo large-scale axial flow, but they can affect secondary flows and WSS directional changes. Overall, helical flow topology is moderately affected by aortic wall displacements, whereas helicity intensity remains almost unchanged. We conclude that CFD simulations with rigid-wall assumption can be a valid approach to study large-scale aortic flows of physiological significance.

Location specific multi-scale characterization and constitutive modeling of pig aorta.

The mechanical and structural behavior of the aorta depend on physiological functions and vary from proximal to distal. Understanding the relation between regionally varying mechanical and multi-scale structural response of aorta can be helpful to assess the disease outcomes. Therefore, this study investigated the variation in mechanical and multi-scale structural properties among the major segments of aorta such as ascending aorta (AA), descending aorta (DA) and abdominal aorta (ABA), and established a relation between mechanical and multi-structural parameters. The obtained results showed significant increase in anisotropy and nonlinearity from proximal to distal aorta. The change in periphery length and radii between load and stress free configuration was also found increasing far from the heart. Opening angle was significantly large for ABA than AA and DA (AA/DA vs ABA; p = 0.001). Mean circumferential residual stretch (ratio of mean periphery length at load and stress free configurations) was found decreasing between AA and DA, and then increasing between DA to ABA and its value was significantly more for ABA (AA vs DA; p = 0.041, AA vs ABA; p = 0.001, DA vs ABA; p = 0.001). The waviness of collagen fibers, collagen fiber content, collagen fibril diameter and total protein content were found significantly increasing from proximal to distal. Pearson correlation test showed a significant linear correlation between variation in mechanical and multi-scale structural parameters over the aortic length. Residual stretch was found positively correlated with collagen fiber content (r = 0.82) whereas opening angel was found positively correlated with total protein content (TPC) (r = 0.76).

Relaxation of thoracic aorta and pulmonary artery rings of marmosets (Callithrix spp.) by endothelium-derived 6-nitrodopamine.

6-Nitrodopamine is a novel catecholamine released by vascular tissues, heart, and vas deferens. The aim of this study was to investigate whether 6-nitrodopamine is released from the thoracic aorta and pulmonary artery rings of marmosets (Callithrix spp.) and to evaluate the relaxing and anti-contractile actions of this catecholamine. Release of 6-nitrodopamine, dopamine, noradrenaline, and adrenaline was assessed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The relaxations induced by 6-nitrodopamine and by the selective dopamine D2 receptor antagonist L-741,626 were evaluated on U-46619 (3 nM)-pre-contracted vessels. The effects of 6-nitrodopamine and L-741,626 on the contractions induced by electric-field stimulation (EFS), dopamine, noradrenaline, and adrenaline were also investigated. Both aorta and pulmonary artery rings exhibited endothelium-dependent release of 6-nitrodopamine, which was significantly reduced by the NO synthesis inhibitor L-NAME. Addition of 6-nitrodopamine or L-741,626 caused concentration-dependent relaxations of both vascular tissues, which were almost abolished by endothelium removal, whereas L-NAME and the soluble guanylate cyclase inhibitor ODQ had no effect on 6-nitrodopamine-induced relaxations. Additionally, pre-incubation with 6-nitrodopamine antagonized the dopamine-induced contractions, without affecting the noradrenaline- and adrenaline-induced contractions. Pre-incubation with L-741,626 antagonized the contractions induced by all catecholamines. The EFS-induced contractions were significantly increased by L-NAME, but unaffected by ODQ. Immunohistochemical assays showed no immunostaining of the neural tissue markers S-100 and calretinin in either vascular tissue. The results indicated that 6-nitrodopamine is the major catecholamine released by marmoset vascular tissues, and it acts as a potent and selective antagonist of dopamine D2-like receptors. 6-nitrodopamine release may be the major mechanism by which NO causes vasodilatation.

Reduction of vascular reactivity in rat aortas following pilocarpine-induced status epilepticus.

OBJECTIVE: The authors investigated changes in vascular reactivity in rats following pilocarpine-induced status epilepticus. METHOD: Male Wistar rats weighing between 250g and 300g were used. Status epilepticus was induced using 385 mg/kg i.p. pilocarpine. After 40 days the thoracic aorta was dissected and divided into 4 mm rings and the vascular smooth muscle reactivity to phenylephrine was evaluated. RESULTS: Epilepsy decreased the contractile responses of the aortic rings to phenylephrine (0.1 nM-300 mM). To investigate if this reduction was induced by increasing NO production with/or hydrogen peroxide L-NAME and Catalase were used. L-NAME (N-nitro-L arginine methyl ester) increased vascular reactivity but the contractile response to phenylephrine increased in the epileptic group. Catalase administration decreased the contractile responses only in the rings of rats with epilepsy. CONCLUSIONS: Our findings demonstrated for the first time that epilepsy is capable of causing a reduction of vascular reactivity in rat aortas. These results suggest that vascular reactivity reduction is associated with increased production of Nitric Oxide (NO) as an organic attempt to avoid hypertension produced by excessive sympathetic activation.

Data-driven generation of 4D velocity profiles in the aneurysmal ascending aorta.

BACKGROUND AND OBJECTIVE: Numerical simulations of blood flow are a valuable tool to investigate the pathophysiology of ascending thoratic aortic aneurysms (ATAA). To accurately reproduce in vivo hemodynamics, computational fluid dynamics (CFD) models must employ realistic inflow boundary conditions (BCs). However, the limited availability of in vivo velocity measurements, still makes researchers resort to idealized BCs. The aim of this study was to generate and thoroughly characterize a large dataset of synthetic 4D aortic velocity profiles sampled on a 2D cross-section along the ascending aorta with features similar to clinical cohorts of patients with ATAA. METHODS: Time-resolved 3D phase contrast magnetic resonance (4D flow MRI) scans of 30 subjects with ATAA were processed through in-house code to extract anatomically consistent cross-sectional planes along the ascending aorta, ensuring spatial alignment among all planes and interpolating all velocity fields to a reference configuration. Velocity profiles of the clinical cohort were extensively characterized by computing flow morphology descriptors of both spatial and temporal features. By exploiting principal component analysis (PCA), a statistical shape model (SSM) of 4D aortic velocity profiles was built and a dataset of 437 synthetic cases with realistic properties was generated. RESULTS: Comparison between clinical and synthetic datasets showed that the synthetic data presented similar characteristics as the clinical population in terms of key morphological parameters. The average velocity profile qualitatively resembled a parabolic-shaped profile, but was quantitatively characterized by more complex flow patterns which an idealized profile would not replicate. Statistically significant correlations were found between PCA principal modes of variation and flow descriptors. CONCLUSIONS: We built a data-driven generative model of 4D aortic inlet velocity profiles, suitable to be used in computational studies of blood flow. The proposed software system also allows to map any of the generated velocity profiles to the inlet plane of any virtual subject given its coordinate set.

Tri-layered constitutive modelling unveils functional differences between the pig ascending and lower thoracic aorta.

The arterial wall's tri-layered macroscopic and layer-specific microscopic structure determine its mechanical properties, which vary at different arterial locations. Combining layer-specific mechanical data and tri-layered modelling, this study aimed to characterise functional differences between the pig ascending (AA) and lower thoracic aorta (LTA). AA and LTA segments were obtained for n=9 pigs. For each location, circumferentially and axially oriented intact wall and isolated layer strips were tested uniaxially and the layer-specific mechanical response modelled using a hyperelastic strain energy function. Then, layer-specific constitutive relations and intact wall mechanical data were combined to develop a tri-layered model of an AA and LTA cylindrical vessel, accounting for the layer-specific residual stresses. AA and LTA behaviours were then characterised for in vivo pressure ranges while stretched axially to in vivo length. The media dominated the AA response, bearing>2/3 of the circumferential load both at physiological (100 mmHg) and hypertensive pressures (160 mmHg). The LTA media bore most of the circumferential load at physiological pressure only (57±7% at 100 mmHg), while adventitia and media load bearings were comparable at 160 mmHg. Furthermore, increased axial elongation affected the media/adventitia load-bearing only at the LTA. The pig AA and LTA presented strong functional differences, likely reflecting their different roles in the circulation. The media-dominated compliant and anisotropic AA stores large amounts of elastic energy in response to both circumferential and axial deformations, which maximises diastolic recoiling function. This function is reduced at the LTA, where the adventitia shields the artery against supra-physiological circumferential and axial loads.

Effect of aging on the biaxial mechanical behavior of human descending thoracic aorta: Experiments and constitutive modeling considering collagen crosslinking.

Collagen crosslinking, an important contributor to the stiffness of soft tissues, was found to increase with aging in the aortic wall. Here we investigated the mechanical properties of human descending thoracic aorta with aging and the role of collagen crosslinking through a combined experimental and modeling approach. A total of 32 samples from 17 donors were collected and divided into three age groups: <40, 40-60 and > 60 years. Planar biaxial tensile tests were performed to characterize the anisotropic mechanical behavior of the aortic samples. A recently developed constitutive model incorporating collagen crosslinking into the two-fiber family model (Holzapfel and Ogden, 2020) was modified to accommodate biaxial deformation of the aorta, in which the extension and rotation kinematics of bonded fibers and crosslinks were decoupled. The mechanical testing results show that the aorta stiffens with aging with a more drastic change in the longitudinal direction, which results in altered aortic anisotropy. Our results demonstrate a good fitting capability of the constitutive model considering crosslinking for the biaxial aortic mechanics of all age groups. Furthermore, constitutive modeling results suggest an increased contribution of crosslinking and strain energy density to the biaxial stress-stretch behaviors with aging and point to excessive crosslinking as a prominent contributor to aortic stiffening.

Quantitative Assessment of Aortic Hemodynamics for Varying Left Ventricular Assist Device Outflow Graft Angles and Flow Pulsation.

Left ventricular assist devices (LVADs) comprise a primary treatment choice for advanced heart failure patients. Treatment with LVAD is commonly associated with complications like stroke and gastro-intestinal (GI) bleeding, which adversely impacts treatment outcomes, and causes fatalities. The etiology and mechanisms of these complications can be linked to the fact that LVAD outflow jet leads to an altered state of hemodynamics in the aorta as compared to baseline flow driven by aortic jet during ventricular systole. Here, we present a framework for quantitative assessment of aortic hemodynamics in LVAD flows realistic human vasculature, with a focus on quantifying the differences between flow driven by LVAD jet and the physiological aortic jet when no LVAD is present. We model hemodynamics in the aortic arch proximal to the LVAD outflow graft, as well as in the abdominal aorta away from the LVAD region. We characterize hemodynamics using quantitative descriptors of flow velocity, stasis, helicity, vorticity and mixing, and wall shear stress. These are used on a set of 27 LVAD scenarios obtained by parametrically varying LVAD outflow graft anastomosis angles, and LVAD flow pulse modulation. Computed descriptors for each of these scenarios are compared against the baseline flow, and a detailed quantitative characterization of the altered state of hemodynamics due to LVAD operation (when compared to baseline aortic flow) is compiled. These are interpreted using a conceptual model for LVAD flow that distinguishes between flow originating from the LVAD outflow jet (and its impingement on the aorta wall), and flow originating from aortic jet during aortic valve opening in normal physiological state.

Regional and directional delamination properties of healthy human ascending aorta and sinotubular junction.

PURPOSE: Acute type A aortic dissection (AD) is a catastrophic event associated with high mortality. Biomechanics can provide an understanding of the forces that lead the initial intimal tear to propagate, resulting in aortic dissection. We previously studied the material properties of normal human aortic roots. In this study, our objective was to determine the regional and directional delamination properties of healthy human ascending aorta (AscAo) and sinotubular junction (STJ). RESULTS: From 19 healthy donor hearts, total 107 samples from the AscAo and STJ were collected and tested along the circumferential and longitudinal directions. Specimens were subjected to uniaxial peeling testing with a manually created tear in the medial layer. The lateral AscAo subregion (greater curvature) had significantly lower delamination strength and dissection energy than anterior, medial, and posterior subregions in the longitudinal direction. Regionally, the delamination strength at AscAo was significantly lower than at STJ overall (p = 0.02) and in circumferential direction (p = 0.02) only. Directionally, the delamination strength at AscAo overall and in the anterior AscAo was significant lower in circumferential direction than longitudinal direction. Dissection energy demonstrated similar regional and directional trend as delamination strength. In addition, both dissection energy and delamination strength were correlated positively with thickness and negatively with age in the AscAo. In addition, the dissection energy was negatively related to stiffness at physiologic mean blood pressure. CONCLUSIONS: The greater curvature of the AscAo had the lowest delamination strength and dissection energy suggesting that region was most vulnerable to dissection propagation distally. Increased thickness of AscAo would be protective of dissection propagation while propagation would be more likely with increased AscAo stiffness.

A detailed analysis in thoracic aorta by means of the entropy generation rate: Prediction of the atherosclerotic lesion.

A detailed numerical analysis is carried out in a real human thoracic aorta by means of the Computational Fluid Dynamics (CFD) for the prediction of the atherosclerosis lesion. Common hemodynamics parameters, such as, the oscillatory shear index (OSI) and the time average wall shear stress (TAWSS) are used for the prediction of the atherosclerosis lesion. Furthermore, the entropy generation rate is considered to obtain the main irreversibilities that occurs inside the thoracic aorta for the prediction of the atherosclerosis lesion. The model considers the blood flow inside the thoracic aorta in an unsteady state. The results show contours of velocity, streams lines, velocity profiles and the comparison of the hemodynamics parameters OSI versus TAWSS. Moreover, contours of the entropy generation rate are showed inside the aorta. The time averaged entropy generation rate (TAEGR) is obtained as a result of the entropy generation analysis. Finally, TAEGR index is compared and discussed with the common hemodynamics parameters, OSI and TAWSS. The accuracy to detect prone locations to atherosclerotic development in the real aorta using the TAEGR in comparison to the OSI and the TAWSS is in good agreement.

Time-course of the human thoracic aorta ageing process assessed using uniaxial mechanical testing and constitutive modelling.

Age-related remodelling of the arterial wall shifts the load bearing from the compliant elastin network to the stiffer collagen fibres. While this phenomenon has been widely investigated in animal models, human studies are lacking due to shortage of donors' arteries. This work aimed to characterise the effect of ageing on the mechanical properties of the human aortic wall in the circumferential direction. N = 127 thoracic aortic rings (age 18-81 years) were subjected to circumferential tensile testing. The tangential elastic modulus (Kθθθθ) was calculated at pressure-equivalent stresses ranging 60-100 mmHg. Further, the mechanical data were fitted using the Holzpafel-Gasser-Ogden hyperelastic strain energy function (HGO-SEF), modelling the superimposed response of an isotropic matrix (elastin) reinforced by collagen fibres. Kθθθθ increased with age across at all considered pressures (p < 0.001), although more strongly at higher pressures. Indeed, the slope of the linear Kθθθθ-pressure relationship increased by 300% from donors <30 to ≥70 years (4.72± 2.95 to 19.06± 6.82 kPa/mmHg, p < 0.001). The HGO-SEF elastin stiffness-like parameter dropped by 31% between 30 and 40 years (p < 0.05) with non-significant changes thereafter. Conversely, changes in HGO-SEF collagen parameters were observed later at age>60 years, with the exponential constant increasing by ∼20-50 times in the investigated age range (p < 0.001). The results provided evidence that the human thoracic aorta undergoes stiffening during its life-course. Constitutive modelling suggested that these changes in arterial mechanics are related to the different degeneration time-courses of elastin and collagen; likely due to considerable fragmentation of elastin first, with the load bearing shifting from the compliant elastin to the stiffer collagen fibres. This process leads to a gradual impairment of the aortic elastic function with age.

Computational fluid dynamics investigation on aortic hemodynamics in double aortic arch before and after ligation surgery.

Double aortic arch (DAA) malformation is one of the reasons for symptomatic vascular rings, the hemodynamics of which is still poorly understood. This study aims to investigate the blood flow characteristics in patient-specific double aortic arches using computational fluid dynamics (CFD). Seven cases of infantile patients with DAA were collected and their computed tomography images were used to reconstruct 3D computational models. A modified Carreau model was used to consider the non-Newtonian effect of blood and a three-element Windkessel model taking the effect of the age of patients into account was applied to reproduce physiological pressure waveforms. Numerical results show that blood flow distribution and energy loss of DAA depends on relative sizes of the two aortic arches and their angles with the ascending aorta. Ligation of either aortic arch increases the energy loss of blood in the DAA, leading to the increase in cardiac workload. Generally, the rising rate of energy loss before and after the surgery is almost linear with the area ratio between the aortic arch without ligation and the ascending aorta.

Viscoelasticity of human descending thoracic aorta in a mock circulatory loop.

Healthy human descending thoracic aortas, obtained during organ donation for transplant and research, were tested in a mock circulatory loop to measure the mechanical response to physiological pulsatile pressure and flow. The viscoelastic properties of the aortic segments were investigated at three different pulse rates. The same aortic segments were also subjected to quasi-static pressure tests in order to identify the aortic dynamic stiffness ratio, which is defined as the ratio between the stiffness in case of pulsatile pressure and the stiffness measured for static pressurization, both at the same value of pressure. The loss factor was also identified. The shape of the deformed aorta under static and dynamic pressure was measured by image processing to verify the compatibility of the end supports with the natural deformation of the aorta in the human body. In addition, layer-specific experiments on 10 human descending thoracic aortas allowed to precisely identify the mass density of the aortic tissue, which is an important parameter in cardiovascular dynamic models.

Direct visualization of interstitial flow distribution in aortic walls.

Vascular smooth muscle cells are exposed to interstitial flow across aortic walls. Fluid shear stress changes the phenotype of smooth muscle cells to the synthetic type; hence, the fast interstitial flow might be related to aortic diseases. In this study, we propose a novel method to directly measure the interstitial flow velocity from the spatiotemporal changes in the concentration of a fluorescent dye. The lumen of a mouse thoracic aorta was filled with a fluorescent dye and pressurized in ex vivo. The flow of the fluorescent dye from the intimal to the adventitial sides was successfully visualized under a two-photon microscope. The flow velocity was determined by applying a one-dimensional advection-diffusion equation to the kymograph obtained from a series of fluorescent images. The results confirmed a higher interstitial flow velocity in the aortic walls under higher intraluminal pressure. A comparison of the interstitial flow velocity in the radial direction showed faster flow on the more intimal side, where hyperplasia is often found in hypertension. These results indicate that the proposed method can be used to visualize the interstitial flow directly and thus, determine the local interstitial flow velocity.

Aortic stiffness is lower when PVAT is included: a novel ex vivo mechanics study.

Perivascular adipose tissue (PVAT) is increasingly recognized as an essential layer of the functional vasculature, being responsible for producing vasoactive substances and assisting arterial stress relaxation. Here, we test the hypothesis that PVAT reduces aortic stiffness. Our model was the thoracic aorta of the male Sprague-Dawley rat. Uniaxial mechanical tests for three groups of tissue were performed: aorta with PVAT attached (+PVAT) or removed (-PVAT), and isolated PVAT (PVAT only). The output of the mechanical test is reported in the form of a Cauchy stress-stretch curve. This work presents a novel, physiologically relevant approach to measure mechanical stiffness ex vivo in isolated PVAT. Low-stress stiffness (E0), high-stress stiffness (E1), and the stress corresponding to a stretch of 1.2 (σ1.2) were measured as metrics of distensibility. The low-stress stiffness was largest in the -PVAT samples and smallest in PVAT only samples. Both the high-stress stiffness and the stress at 1.2 stretch were significantly higher in -PVAT samples when compared with +PVAT samples. Taken together, these results suggest that -PVAT samples are stiffer (less distensible) both at low stress (not significant) as well as at high stress (significant) when compared with +PVAT samples. These conclusions are supported by the results of the continuum mechanics material model that we also used to interpret the same experimental data. Thus, tissue stiffness is significantly lower when considering PVAT as part of the aortic wall. As such, PVAT should be considered as a target for improving vascular function in diseases with elevated aortic stiffness, including hypertension.NEW & NOTEWORTHY We introduce a novel and physiologically relevant way of measuring perivascular adipose tissue (PVAT) mechanical stiffness which shows that PVAT's low, yet measurable, stiffness is linearly correlated with the amount of collagen fibers present within the tissue. Including PVAT in the measurement of the aortic wall's mechanical behavior is important, and it significantly affects the resulting metrics by decreasing aortic stiffness.