Testosterone deficiency promotes arterial stiffening independent of sex chromosome complement.

BACKGROUND: Sex hormones and sex chromosomes play a vital role in cardiovascular disease. Testosterone plays a crucial role in men's health. Lower testosterone level is associated with cardiovascular and cardiometabolic diseases, including inflammation, atherosclerosis, and type 2 diabetes. Testosterone replacement is beneficial or neutral to men's cardiovascular health. Testosterone deficiency is associated with cardiovascular events. Testosterone supplementation to hypogonadal men improves libido, increases muscle strength, and enhances mood. We hypothesized that sex chromosomes (XX and XY) interaction with testosterone plays a role in arterial stiffening. METHODS: We used four core genotype male mice to understand the inherent contribution of sex hormones and sex chromosome complement in arterial stiffening. Age-matched mice were either gonadal intact or castrated at eight weeks plus an additional eight weeks to clear endogenous sex hormones. This was followed by assessing blood pressure, pulse wave velocity, echocardiography, and ex vivo passive vascular mechanics. RESULTS: Arterial stiffening but not blood pressure was more significant in castrated than testes-intact mice independent of sex chromosome complement. Castrated mice showed a leftward shift in stress-strain curves and carotid wall thinning. Sex chromosome complement (XX) in the absence of testosterone increased collagen deposition in the aorta and Kdm6a gene expression. CONCLUSION: Testosterone deprivation increases arterial stiffening and vascular wall remodeling. Castration increases Col1α1 in male mice with XX sex chromosome complement. Our study shows decreased aortic contractile genes in castrated mice with XX than XY sex chromosomes.

Cardiovascular disease is the leading cause of death worldwide. Cardiovascular disease presents differently in men and women. While men develop plaque buildup in large arteries, women develop buildup in the microvessels in the heart. Arterial stiffening, which is the hardening of arteries, increases with age in both men and women. Aging, coupled with the decline in sex hormones, exacerbates cardiovascular disease in women compared to men. Men with XY sex chromosomes have higher circulating testosterone, while women with XX sex chromosomes have increased circulating estradiol. The potential benefits of sex hormone replacement therapy are shown in men and women. Indeed, testosterone replacement deficiency is associated with adverse cardiovascular outcomes in men. Whether adverse events are dependent or independent of sex hormones' interaction with sex chromosomes is unknown. This study used the four core genotype mice comprising males with either XX or XY sex chromosome complement. We show castration increases arterial stiffening and collagen deposition on the arterial wall. We also identified the escapee and smooth muscle contractile genes that may play a role in arterial stiffening. Our data suggests that testosterone deprivation mediates arterial stiffening and remodeling.

Impact of cryopreservation on elastomuscular artery mechanics.

Low temperatures slow or halt undesired biological and chemical processes, protecting cells, tissues, and organs during storage. Cryopreservation techniques, including controlled media exchange and regulated freezing conditions, aim to mitigate the physical consequences of freezing. Dimethyl sulfoxide (DMSO), for example, is a penetrating cryoprotecting agent (CPA) that minimizes ice crystal growth by replacing intracellular water, while polyvinyl alcohol (PVA) is a nonpenetrating CPA that prevents recrystallization during thawing. Since proteins and ground substance dominate the passive properties of soft biological tissues, we studied how different freezing rates, storage temperatures, storage durations, and the presence of cryoprotecting agents (5% [v/v] DMSO + 1 mg/mL PVA) impact the histomechanical properties of the internal thoracic artery (ITA), a clinically relevant blood vessel with both elastic and muscular characteristics. Remarkably, biaxial mechanical analyses failed to reveal significant differences among the ten groups tested, suggesting that mechanical properties are virtually independent of the cryopreservation technique. Scanning electron microscopy revealed minor CPA-independent delamination in rapidly frozen samples, while cryoprotected ITAs had better post-thaw viability than their unprotected counterparts using methyl thiazole-tetrazolium (MTT) metabolic assays, especially when frozen at a controlled rate. These results can be used to inform ongoing and future studies in vascular engineering, physiology, and mechanics.

Mechanical characterization and torsional buckling of pediatric cardiovascular materials.

In complex cardiovascular surgical reconstructions, conduit materials that avoid possible large-scale structural deformations should be considered. A fundamental mode of mechanical complication is torsional buckling which occurs at the anastomosis site due to the mechanical instability, leading surgical conduit/patch surface deformation. The objective of this study is to investigate the torsional buckling behavior of commonly used materials and to develop a practical method for estimating the critical buckling rotation angle under physiological intramural vessel pressures. For this task, mechanical tests of four clinically approved materials, expanded polytetrafluoroethylene (ePTFE), Dacron, porcine and bovine pericardia, commonly used in pediatric cardiovascular surgeries, are conducted (n = 6). Torsional buckling initiation tests with n = 4 for the baseline case (L = 7.5 cm) and n = 3 for the validation of ePTFE (L = 15 cm) and Dacron (L = 15 cm and L = 25 cm) for each are also conducted at low venous pressures. A practical predictive formulation for the buckling potential is proposed using experimental observations and available theory. The relationship between the critical buckling rotation angle and the lumen pressure is determined by balancing the circumferential component of the compressive principal stress with the shear stress generated by the modified critical buckling torque, where the modified critical buckling torque depends linearly on the lumen pressure. While the proposed technique successfully predicted the critical rotation angle values lying within two standard deviations of the mean in the baseline case for all four materials at all lumen pressures, it could reliably predict the critical buckling rotation angles for ePTFE and Dacron samples of length 15 cm with maximum relative errors of 31% and 38%, respectively, in the validation phase. However, the validation of the performance of the technique demonstrated lower accuracy for Dacron samples of length 25 cm at higher pressure levels of 12 mmHg and 15 mmHg. Applicable to all surgical materials, this formulation enables surgeons to assess the torsional buckling potential of vascular conduits noninvasively. Bovine pericardium has been found to exhibit the highest stability, while Dacron (the lowest) and porcine pericardium have been identified as the least stable with the (unitless) torsional buckling resistance constants, 43,800, 12,300 and 14,000, respectively. There was no significant difference between ePTFE and Dacron, and between porcine and bovine pericardia. However, both porcine and bovine pericardia were found to be statistically different from ePTFE and Dacron individually (p < 0.0001). ePTFE exhibited highly nonlinear behavior across the entire strain range [0, 0.1] (or 10% elongation). The significant differences among the surgical materials reported here require special care in conduit construction and anastomosis design.

Uncertainty quantification of the wall thickness and stiffness in an idealized dissected aorta.

Personalized treatment informed by computational models has the potential to markedly improve the outcome for patients with a type B aortic dissection. However, existing computational models of dissected walls significantly simplify the characteristic false lumen, tears and/or material behavior. Moreover, the patient-specific wall thickness and stiffness cannot be accurately captured non-invasively in clinical practice, which inevitably leads to assumptions in these wall models. It is important to evaluate the impact of the corresponding uncertainty on the predicted wall deformations and stress, which are both key outcome indicators for treatment optimization. Therefore, a physiology-inspired finite element framework was proposed to model the wall deformation and stress of a type B aortic dissection at diastolic and systolic pressure. Based on this framework, 300 finite element analyses, sampled with a Latin hypercube, were performed to assess the global uncertainty, introduced by 4 uncertain wall thickness and stiffness input parameters, on 4 displacement and stress output parameters. The specific impact of each input parameter was estimated using Gaussian process regression, as surrogate model of the finite element framework, and a δ moment-independent analysis. The global uncertainty analysis indicated minor differences between the uncertainty at diastolic and systolic pressure. For all output parameters, the 4th quartile contained the major fraction of the uncertainty. The parameter-specific uncertainty analysis elucidated that the material stiffness and relative thickness of the dissected membrane were the respective main determinants of the wall deformation and stress. The uncertainty analysis provides insight into the effect of uncertain wall thickness and stiffness parameters on the predicted deformation and stress. Moreover, it emphasizes the need for probabilistic rather than deterministic predictions for clinical decision making in aortic dissections.

Testosterone Deficiency Promotes Arterial Stiffening Independent of Sex Chromosome Complement.

Background: Testosterone plays a vital role in men's health. Lower testosterone level is associated with cardiovascular and cardiometabolic diseases, including inflammation, atherosclerosis, and type 2 diabetes. Testosterone replacement is beneficial or neutral to men's cardiovascular health. Testosterone deficiency is associated with cardiovascular events. Testosterone supplementation to hypogonadal men improves libido, increases muscle strength, and enhances mood. We hypothesized that sex chromosomes (XX and XY) interaction with testosterone plays a role in arterial stiffening. Methods: We used four core genotype male mice to understand the inherent contribution of sex hormones and sex chromosome complement in arterial stiffening. Age-matched mice were either gonadal intact or castrated for eight weeks, followed by an assessment of blood pressure, pulse wave velocity, echocardiography, and ex vivo passive vascular mechanics. Results: Arterial stiffening but not blood pressure was more significant in castrated than testes-intact mice independent of sex chromosome complement. Castrated mice showed a leftward shift in stress-strain curves and carotid wall thinning. Sex chromosome complement (XX) in the absence of testosterone increased collagen deposition in the aorta and Kdm6a gene expression. Conclusion: Testosterone deprivation increases arterial stiffening and vascular wall remodeling. Castration increases Col1α1 in male mice with XX sex chromosome complement. Our study shows decreased aortic contractile genes in castrated mice with XX than XY sex chromosomes.

Improving the accuracy of computational fluid dynamics simulations of coiled cerebral aneurysms using finite element modeling.

Cerebral aneurysms are a serious clinical challenge, with ∼half resulting in death or disability. Treatment via endovascular coiling significantly reduces the chances of rupture, but the techniquehas failure rates of ∼20 %. This presents a pressing need to develop a method fordetermining optimal coildeploymentstrategies. Quantification of the hemodynamics of coiled aneurysms using computational fluid dynamics (CFD) has the potential to predict post-treatment outcomes, but representing the coil mass in CFD simulations remains a challenge. We use the Finite Element Method (FEM) for simulating patient-specific coil deployment for n = 4 ICA aneurysms for which 3D printed in vitro models were also generated, coiled, and scanned using ultra-high resolution synchrotron micro-CT. The physical and virtual coil geometries were voxelized onto a binary structured grid and porosity maps were generated for geometric comparison. The average binary accuracy score is 0.8623 and the average error in porosity map is 4.94 %. We then conduct patient-specific CFD simulations of the aneurysm hemodynamics using virtual coils geometries, micro-CT generated oil geometries, and using the porous medium method to represent the coil mass. Hemodynamic parameters including Neck Inflow Rate (Qneck) and Wall Shear Stress (WSS) were calculated for each of the CFD simulations. The average relative error in Qneck and WSS from CFD using FEM geometry were 6.6 % and 21.8 % respectively, while the error from CFD using a porous media approximation resulted in errors of 55.1 % and 36.3 % respectively; demonstrating a marked improvement in the accuracy of CFD simulations using FEM generated coil geometries.

Ontogenetic scaling of the baroreflex function in the green iguana (Iguana iguana).

Large body mass (Mb) in vertebrates is associated with longer pulse intervals between heartbeats (PI) and thicker arterial walls. Longer PI increases the time for diastolic pressure decay, possibly resulting in loss of cardiac energy as "oscillatory power," whereas thicker arterial walls may affect the transmission of impulses and sensing of pressure fluctuations thus impairing baroreflex function. We aimed to investigate the effect of growth on the relative cardiac energy loss and baroreflex function. We predicted that 1) the relative use of cardiac energy should be preserved with increased time constant for pressure decay (τ = vascular resistance × compliance) and 2) if arterial circumferential distensibility does not change, baroreflex function should be unaltered with Mb. To test these hypotheses, we used green iguanas (Iguana iguana) weighing from 0.03 to 1.34 kg (43-fold increment in Mb). PI (P = 0.037) and τ (P = 0.035) increased with Mb, whereas the oscillatory power fraction (P = 0.245) was unrelated to it. Thus, the concomitant alterations of τ and PI allowed the conservation of cardiac energy in larger lizards. Larger animals had thicker arterial walls (P = 0.0007) and greater relative collagen content (P = 0.022). Area compliance scaled positively to Mb (P = 0.045), though circumferential distensibility (P = 0.155) and elastic modulus (P = 0.762) were unaltered. In addition, baroreflex sensitivity, measured by both the pharmacological (P = 0.152) and sequence methods (P = 0.088), and the baroreflex effectiveness index (P = 0.306) were also unrelated to Mb. Therefore, changes in arterial morphology did not affect circumferential distensibility and presumably sensing of pressure fluctuation, and the cardiovagal baroreflex is preserved across different Mb.

Longitudinal histomechanical heterogeneity of the internal thoracic artery.

The internal thoracic artery (ITA) is the principal choice for coronary artery bypass grafting (CABG) due to its mechanical compatibility, histological composition, anti-thrombogenic lumen, and single anastomotic junction. Originating at the subclavian artery, traversing the thoracic cavity, and terminating at the superior epigastric and musculophrenic bifurcation, bilateral ITAs follow a protracted circuitous pathway. The physiological hemodynamics, anatomical configuration, and perivascular changes that occur throughout this length influence the tissue's microstructure and gross mechanical properties. Since histomechanics play a major role in premature graft failure we used inflation-extension testing to quantify the regional material and biaxial mechanical properties at four distinct locations along the left (L) and right (R) ITA and fit the results to a structurally-motivated constitutive model. Our comparative analysis of 44 vessel segments revealed a significant increase in the amount of collagen but not smooth muscle and a significant decrease in elastin and elastic lamellae present with distance from the heart. A subsequent decrease in the total deformation energy and isotropic contribution to the strain energy was present in the LITA but not RITA. Circumferential stress and compliance generally decreased along the length of the LITA while axial stress increased in the RITA. When comparing RITAs to LITAs, some morphological and histological differences were found in proximal sections while distal sections revealed differences predominantly in compliance and axial stress. Overall, this information can be used to better guide graft selection, graft preparation, and xenograft-based tissue-engineering strategies for CABG.

Fetal Undernutrition Induces Resistance Artery Remodeling and Stiffness in Male and Female Rats Independent of Hypertension.

Fetal undernutrition programs hypertension and cardiovascular diseases, and resistance artery remodeling may be a contributing factor. We aimed to assess if fetal undernutrition induces resistance artery remodeling and the relationship with hypertension. Sprague-Dawley dams were fed ad libitum (Control) or with 50% of control intake between days 11 and 21 of gestation (maternal undernutrition, MUN). In six-month-old male and female offspring we assessed blood pressure (anesthetized and tail-cuff); mesenteric resistance artery (MRA) structure and mechanics (pressure myography), cellular and internal elastic lamina (IEL) organization (confocal microscopy) and plasma MMP-2 and MMP-9 activity (zymography). Systolic blood pressure (SBP, tail-cuff) and plasma MMP activity were assessed in 18-month-old rats. At the age of six months MUN males exhibited significantly higher blood pressure (anesthetized or tail-cuff) and plasma MMP-9 activity, while MUN females did not exhibit significant differences, compared to sex-matched controls. MRA from 6-month-old MUN males and females showed a smaller diameter, reduced adventitial, smooth muscle cell density and IEL fenestra area, and a leftward shift of stress-strain curves. At the age of eighteen months SBP and MMP-9 activity were higher in both MUN males and females, compared to sex-matched controls. These data suggest that fetal undernutrition induces MRA inward eutrophic remodeling and stiffness in both sexes, independent of blood pressure level. Resistance artery structural and mechanical alterations can participate in the development of hypertension in aged females and may contribute to adverse cardiovascular events associated with low birth weight in both sexes.

Human In Vitro Model Mimicking Material-Driven Vascular Regeneration Reveals How Cyclic Stretch and Shear Stress Differentially Modulate Inflammation and Matrix Deposition.

Resorbable synthetic scaffolds designed to regenerate living tissues and organs inside the body have emerged as a clinically attractive technology to replace diseased blood vessels. However, mismatches between scaffold design and in vivo hemodynamic loading (i.e., cyclic stretch and shear stress) can result in aberrant inflammation and adverse tissue remodeling, leading to premature graft failure. Yet, the underlying mechanisms remain elusive. Here, a human in vitro model is presented that mimics the transient local inflammatory and biomechanical environments that drive scaffold-guided tissue regeneration. The model is based on the coculture of human (myo)fibroblasts and macrophages in a bioreactor platform that decouples cyclic stretch and shear stress. Using a resorbable supramolecular elastomer as the scaffold material, it is revealed that cyclic stretch initially reduces proinflammatory cytokine secretion and, especially when combined with shear stress, stimulates IL-10 secretion. Moreover, cyclic stretch stimulates downstream (myo)fibroblast proliferation and matrix deposition. In turn, shear stress attenuates cyclic-stretch-induced matrix growth by enhancing MMP-1/TIMP-1-mediated collagen remodeling, and synergistically alters (myo)fibroblast phenotype when combined with cyclic stretch. The findings suggest that shear stress acts as a stabilizing factor in cyclic stretch-induced tissue formation and highlight the distinct roles of hemodynamic loads in the design of resorbable vascular grafts.

Multiscale Modeling Framework of Ventricular-Arterial Bi-directional Interactions in the Cardiopulmonary Circulation.

Ventricular-arterial coupling plays a key role in the physiologic function of the cardiovascular system. We have previously described a hybrid lumped-finite element (FE) modeling framework of the systemic circulation that couples idealized FE models of the aorta and the left ventricle (LV). Here, we describe an extension of the lumped-FE modeling framework that couples patient-specific FE models of the left and right ventricles, aorta and the large pulmonary arteries in both the systemic and pulmonary circulations. Geometries of the FE models were reconstructed from magnetic resonance (MR) images acquired in a pediatric patient diagnosed with pulmonary arterial hypertension (PAH). The modeling framework was calibrated with pressure waveforms acquired in the heart and arteries by catheterization as well as ventricular volume and arterial diameter waveforms measured from MR images. The calibrated model hemodynamic results match well with the clinically-measured waveforms (volume and pressure) in the LV and right ventricle (RV) as well as with the clinically-measured waveforms (pressure and diameter) in the aorta and main pulmonary artery. The calibrated framework was then used to simulate three cases, namely, (1) an increase in collagen in the large pulmonary arteries, (2) a decrease in RV contractility, and (3) an increase in the total pulmonary arterial resistance, all characteristics of progressive PAH. The key finding from these simulations is that hemodynamics of the pulmonary vasculature and RV wall stress are more sensitive to vasoconstriction with a 10% of reduction in the lumen diameter of the distal vessels than a 67% increase in the proximal vessel's collagen mass.

On the uniform stress/uniform stretch states of prestressed arteries.

This work examines the mechanics of the circumferentially prestressed N-layer artery, subject to axial tethering force and the internal pressure of blood, focusing on the uniform stretch state, the uniform circumferential stress states and the transitional states between them. Under increasing pressure the ith layer is shown to experience five distinct stages, two of which are the uniform stretch state and the uniform circumferential stress state. For arbitrary strain energy density, simple analytical expressions are presented for the stress distributions and the internal pressure at these specialized states. For the 1-layer, uniform tubular model of an artery without axial tethering force, the results coincide with those of Destrade et al. (2012). For the 2-layer composite tube, which models the mechanically significant medial and adventitial layers of large elastic arteries, numerical solutions are obtained employing two microstructurally based constitutive models for medial and adventitial arterial tissues, respectively. These results indicate that the uniform stretch state, the uniform circumferential stress state of the medial layer, and the uniform circumferential stress state of the adventitial layer occur at the diastolic blood pressure, the mean blood pressure, and the systolic blood pressure, respectively.

Arterial Wall Properties in Men and Women: Hemodynamic Analysis and Clinical Implications.

The properties of arterial walls are dictated by their underlying structure, which is responsible for the adequate perfusion of conduit branching arteries and their vascular beds. Beginning with the mechanobiology of arteries in terms of their composition and individual contributions to overall viscoelastic behavior in men and women, pressure-flow relations are analyzed and noted in terms of sex differences. Hemodynamic function in terms of indices of vascular stiffness-such as pressure-strain elastic modulus, pulse wave velocity, augmentation index, and cardio-ankle vascular index-are evaluated. They all showed differences between the sexes, and these differences also were shown among people of different cultures. Recent studies also showed, in heart failure patients, a comparatively greater increase in peripheral resistance and a greater decreased arterial compliance in women. Wave separation into forward and reflected waves allows elucidation of mechanical and drug-treated similarities and differences in induced hypertension. This may provide insight into treatment strategy in terms of improving mechanobiology and designing drug therapy for the sexes. Finally, modeling studies are useful in identifying how arterial compliance and its pressure dependence can be better used in differentiating aging- and hypertension-induced changes that differentially affect the sexes.

Quantitative Vascular Evaluation: From Laboratory Experiments to Point-of-Care Patient (Experimental Approach).

This paper illustrates the evolution of our knowledge of arterial mechanics from our initial research works up to the present time. Several techniques focusing on this topic in terms of our experience are discussed. An interdisciplinary team composed by different institutions from Argentina, Uruguay, France and Spain was created to conduct research, to train human resources and to fulfill the inevitable social role of gaining access to technological innovation to improve public health.

Challenges in chemotherapy delivery: comparison of standard chemotherapy delivery to locoregional vascular mass fluid transfer.

Standard intravenous chemotherapy delivery to neoplasms relies on simple diffusion gradients from the intravascular to the interstitial space. Systemic perfusion creates untoward effects on normal tissue limiting both concentration and exposure times. Regional intra-arterial therapy is limited by drug recirculation and vascular isolation repeatability and does not address the interstitial microenvironment. Barriers to delivery relate to chaotic vascular architecture, heterogeneous fluid flux, increased interstitial and variable solid tumor pressure and ischemia. To address these difficulties, a delivery system was developed allowing mass fluid transfer of chemotherapeutic agents into the interstitium. This implantable, reusable system is comprised of multiple independently steerable balloons and catheters capable of controlling the locoregional hydraulic and oncotic forces across the vascular endothelium.

Heart-lung interactions in acute respiratory distress syndrome: pathophysiology, detection and management strategies.

Acute respiratory distress syndrome (ARDS) is the most severe form of acute respiratory failure characterized by diffuse alveolar and endothelial damage. The severe pathophysiological changes in lung parenchyma and pulmonary circulation together with the effects of positive pressure ventilation profoundly affect heart lung interactions in ARDS. The term pulmonary vascular dysfunction (PVD) refers to the specific involvement of the vascular compartment in ARDS and is expressed clinically by an increase in pulmonary arterial (PA) pressure and pulmonary vascular resistance both affecting right ventricular (RV) afterload. When severe, PVD can lead to RV failure which is associated to an increased mortality. The effect of PVD on RV function is not only a consequence of increased pulmonary vascular resistance as afterload is a much more complex phenomenon that includes all factors that oppose efficient ventricular ejection. Impaired pulmonary vascular mechanics including increased arterial elastance and augmented wave-reflection phenomena are commonly seen in ARDS and can additionally affect RV afterload. The use of selective pulmonary vasodilators and lung protective mechanical ventilation strategies are therapeutic interventions that can ameliorate PVD. Prone positioning and the open lung approach (OLA) are especially attractive strategies to improve PVD due to their effects on increasing functional lung volume. In this review we will describe some pathophysiological aspects of heart-lung interactions during the ventilatory support of ARDS, its clinical assessment and discuss therapeutic interventions to prevent the occurrence and progression of PVD and RV failure.

In vitro validation of measurement of volume elastic modulus using photoplethysmography.

Arterial stiffness (AS) is one of the earliest detectable symptoms of cardiovascular diseases and their progression. Current AS measurement methods provide an indirect and qualitative estimation of AS. The purpose of this study is to explore the utilisation of Photoplethysmography (PPG) as a measure of volumetric strain in providing a direct quantification of the Volume Elastic modulus (Ev). An in vitro experimental setup was designed using an arterial model to simulate the human circulation in health (Model 2) and disease (Model 1). Flow, pressure, and PPG signals were recorded continuously under varied conditions of flow dynamics. The obtained Ev values were validated with the gold standard mechanical testing techniques. Values obtained from both methods had no significant difference for both models with a percent error of 0.26% and 1.9% for Model 1 and Model 2, respectively. This study shows that PPG and pressure signals can provide a direct measure of AS in an in vitro setup. With emerging noninvasive pressure measurement methods, this research paves the way for the direct quantification of AS in vivo.

Experimental and numerical studies of two arterial wall delamination modes.

Arterial wall dissection, which results from various pathophysiological processes, can lead to the occurrence of large area delamination in the aortic wall that can potentially block blood flow and lead to deleterious clinical conditions. Despite its critical clinical relevance, few studies have focused on investigating the failure mode of delamination in the arterial wall. In this study, we quantify the energy release rate of the medial layer of a porcine abdominal aorta via two delamination experiments: the mixed-mode delamination experiment and the "T"-shaped delamination experiment. A cohesive zone model (CZM) is applied to simulate the arterial wall delamination and Holzapfel-Gasser-Ogden (HGO) material model is used to capture the bulk arterial material behavior. A set of parameter values for the HGO and CZM models are identified through matching simulation predictions of the load vs. load-point displacement curve with experimental measurements. Then the parameter values and critical energy release rates obtained from experiments are used as input data for simulation predictions for two arterial wall delamination experiments. The simulation predictions show that the delamination front matches well with experimental measurements. Moreover, the mixed-mode delamination experiment reveals a shear mode-dominated failure event, whereas the "T"-shaped delamination experiment is an opening failure process. The integration of experimental data and numerical predictions of arterial delamination events provides a comprehensive description of distinct failure modes and aids in the prediction of aortic dissection.

Role of fetal nutrient restriction and postnatal catch-up growth on structural and mechanical alterations of rat aorta.

KEY POINTS: Intrauterine growth restriction (IUGR), induced by maternal undernutrition, leads to impaired aortic development. This is followed by hypertrophic remodelling associated with accelerated growth during lactation. Fetal nutrient restriction is associated with increased aortic compliance at birth and at weaning, but not in adult animals. This mechanical alteration may be related to a decreased perinatal collagen deposition. Aortic elastin scaffolds purified from young male and female IUGR animals also exhibit increased compliance, only maintained in adult IUGR females. These mechanical alterations may be related to differences in elastin deposition and remodelling. Fetal undernutrition induces similar aortic structural and mechanical alterations in young male and female rats. Our data argue against an early mechanical cause for the sex differences in hypertension development induced by maternal undernutrition. However, the larger compliance of elastin in adult IUGR females may contribute to the maintenance of a normal blood pressure level. ABSTRACT: Fetal undernutrition programmes hypertension development, males being more susceptible. Deficient fetal elastogenesis and vascular growth is a possible mechanism. We investigated the role of aortic mechanical alterations in a rat model of hypertension programming, evaluating changes at birth, weaning and adulthood. Dams were fed ad libitum (Control) or 50% of control intake during the second half of gestation (maternal undernutrition, MUN). Offspring aged 3 days, 21 days and 6 months were studied. Blood pressure was evaluated in vivo. In the thoracic aorta we assessed gross structure, mechanical properties (intact and purified elastin), collagen and elastin content and internal elastic lamina (IEL) organization. Only adult MUN males developed hypertension (systolic blood pressure: MUNmales  = 176.6 ± 5.6 mmHg; Controlmales  = 136.1 ± 4.9 mmHg). At birth MUN rats were lighter, with smaller aortic cross-sectional area (MUNmales  = (1.51 ± 0.08) × 105  µm2 , Controlmales  = (2.8 ± 0.04) × 105  µm2 ); during lactation MUN males and females exhibited catch-up growth and aortic hypertrophy (MUNmales  = (14.5 ± 0.5) × 105  µm2 , Controlmales  = (10.4 ± 0.9) × 105  µm2 ), maintained until adulthood. MUN aortas were more compliant until weaning (functional stiffness: MUNmales  = 1.0 ± 0.04; Controlmales  = 1.3 ± 0.03), containing less collagen with larger IEL fenestrae, returning to normal in adulthood. Purified elastin from young MUN offspring was more compliant in both sexes; only MUN adult females maintained larger elastin compliance (slope: MUNfemales  = 24.1 ± 1.9; Controlfemales  = 33.3 ± 2.8). Fetal undernutrition induces deficient aortic development followed by hypertrophic remodelling and larger aortic compliance in the perinatal period, with similar alterations in collagen and elastin in both sexes. The observed alterations argue against an initial mechanical cause for sex differences in hypertension development. However, the maintenance of high elastin compliance in adult females might protect them against blood pressure rise.