Mechanical, structural, and morphological differences in the iliac arteries.

Iliac arteries play a crucial role in peripheral blood circulation. They are susceptible to various diseases, including aneurysms and atherosclerosis. Structure, material properties, and biomechanical forces acting on different regions of the iliac vasculature may contribute to the localization and progression of these pathologies. We examined 33 arterial specimens from common iliac (CI), external iliac (EI), and internal iliac (II) arteries obtained from 11 human donors (62 ± 12 years). We conducted morphometric, mechanical, and structural analyses using planar biaxial tests, constitutive modeling, and bi-directional histology on transverse and axial sections. The iliac arteries exhibited increased tortuosity and varying disease distribution with age. CI and II arteries displayed non-uniform age-related disease progression around their circumference, while EI remained healthy even in older individuals. Trends in load-free and stress-free thickness varied along the iliac vasculature. Longitudinally, EI exhibited the highest compliance compared to other iliac vessels. In contrast, CI was stiffest longitudinally, and EI was the stiffest circumferentially. Material parameters for all iliac vessels are reported for four common constitutive relations. Elastin near the internal elastic lamina displayed greater waviness in EI and II compared to CI. Also, EI had the least glycosaminoglycans (GAGs) and the highest elastin content. Our findings highlight variations in the morphological, mechanical, and structural properties of iliac arteries along their length. This data can inform vascular disease development and computational studies, and guide the development of biomimetic repair materials and devices tailored to specific iliac locations, improving vascular repair strategies.

Structural and Mechanical Properties of Human Superficial Femoral and Popliteal Arteries.

The femoropopliteal artery (FPA) is the main artery in the lower limb. It supplies blood to the leg muscles and undergoes complex deformations during limb flexion. Atherosclerotic disease of the FPA (peripheral arterial disease, PAD) is a major public health burden, and despite advances in surgical and interventional therapies, the clinical outcomes of PAD repairs continue to be suboptimal, particularly in challenging calcified lesions and biomechanically active locations. A better understanding of human FPA mechanical and structural characteristics in relation to age, risk factors, and the severity of vascular disease can help develop more effective and longer-lasting treatments through computational modeling and device optimization. This review aims to summarize recent research on the main biomechanical and structural properties of human superficial femoral and popliteal arteries that comprise the FPA and describe their anatomy, composition, and mechanical behavior under different conditions.

Variability in structure, morphology, and mechanical properties of the descending thoracic and infrarenal aorta around their circumference.

Aortic diseases, such as aneurysms, atherosclerosis, and dissections, demonstrate a preferential development and progression around the aortic circumference, resulting in a highly heterogeneous disease state around the circumference. Differences in the aorta's structural composition and mechanical properties may be partly responsible for this phenomenon. Our goal in this study was to analyze the mechanical and structural properties of the human aorta at its lateral, anterior, posterior, and medial quadrants in two regions prone to circumferentially inhomogeneous diseases, descending Thoracic Aorta (TA) and Infrarenal Aorta (IFR). Human aortas were obtained from 10 donors (64 ± 11 years) and dissected from their loose surrounding tissue. Mechanical properties were determined in all four quadrants of TA and IFR using planar biaxial testing and fitted to three common constitutive models. The structure of tissues was assessed using Movat Pentachrome stained histology slides. We observed that the anterior quadrant exhibited the greatest thickness, followed by the lateral region, in both the TA and IFR. In TA, the posterior wall appeared as the stiffest location in most samples, while in IFR, the anterior wall was the stiffest. We observed a higher glycosaminoglycans content in the lateral and posterior regions of the IFR. We found elastin density to be similar in TA lateral, anterior, and posterior quadrants, while in IFR, the anterior region demonstrated the highest elastin density. Despite significant variations between subjects, this study highlights the distinct morphometrical, mechanical, and structural properties between the quadrants of both TA and IFR.

Safe balloon inflation parameters for resuscitative endovascular balloon occlusion of the aorta.

BACKGROUND: Noncompressible hemorrhage is a leading cause of preventable death in civilian and military trauma populations. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a promising method for controlling noncompressible hemorrhage, but safe balloon inflation parameters are not well defined. Our goal was to determine the balloon inflation parameters associated with benchtop flow occlusion and aortic/balloon rupture in ex vivo human aortas and test the hypothesis that optimal balloon inflation characteristics depend on systolic pressure and subject demographics. METHODS: Aortic occlusion parameters in human thoracic aortas (TAs) and abdominal aortas (AAs) from 79 tissue donors (median ± SD age, 52 ± 18 years [range, 13-75 years]; male, 52; female, 27) were recorded under 100/40, 150/40, and 200/40 mm Hg flow pressures for ER-REBOA and Coda balloons. Rupture tests were done with Coda balloons only without flow. RESULTS: In the TA, the average balloon inflation volumes and pressures resulting in 100/40 mm Hg flow occlusion were 11.7 ± 3.8 mL and 174 ± 65 mm Hg for the ER-REBOA, and 10.6 ± 4.3 mL and 94 ± 57 mm Hg for the Coda balloons. In the AA, these values were 6.2 ± 2.6 mL and 110 ± 47 mm Hg for the ER-REBOA, and 5.9 ± 2.2 mL and 71 ± 30 mm Hg for the Coda. The average balloon inflation parameters associated with aortic/Coda balloon rupture were 39.1 ± 6.5 mL and 1,284 ± 385 mm Hg in the TA, and 27.7 ± 7.7 mL and 1,410 ± 483 mm Hg in the AA. Age, sex, and systolic pressure all had significant effects on balloon occlusion and rupture parameters. CONCLUSION: Optimal balloon inflation parameters depend on anatomical, physiological, and demographic characteristics. Pressure-guided rather than volume-guided balloon inflation may reduce the risk of aortic rupture. These results can be used to help improve the safety of REBOA procedures and devices.

Endovascular Repair of Blunt Thoracic Aortic Trauma is Associated With Increased Left Ventricular Mass, Hypertension, and Off-target Aortic Remodeling.

BACKGROUND: Aortic elasticity creates a cushion that protects the heart from pressure injury, and a recoil that helps perfuse the coronary arteries. TEVAR has become first-line therapy for many aortic pathologies including trauma, but stent-grafts stiffen the aorta and likely increase LV afterload. OBJECTIVE: Test the hypothesis that trauma TEVAR is associated with LV mass increase and adverse off-target aortic remodeling. METHODS: Computed Tomography Angiography (CTA) scans of 20 trauma TEVAR patients (17 M/3 F) at baseline [age 34.9 ±â€Š18.5 (11.4-71.5) years] and 5.1 ±â€Š3.1 (1.1-12.3) years after repair were used to measure changes in LV mass, LV mass index, and diameters and lengths of the ascending thoracic aorta (ATA). Measurements were compared with similarly-aged control patients without aortic repair (21 M/21 F) evaluated at similar follow-ups. RESULTS: LV mass and LV mass index of TEVAR patients increased from 138.5 ±â€Š39.6 g and 72.35 ±â€Š15.17 g/m2 to 173.5 ±â€Š50.1 g and 85.48 ±â€Š18.34 g/m2 at the rate of 10.03 ±â€Š12.79 g/yr and 6.25 ±â€Š10.28 g/m2/yr, whereas in control patients LV characteristics did not change. ATA diameters of TEVAR patients increased at a rate of 0.60 ±â€Š0.80 mm/yr, which was 2.4-fold faster than in controls. ATA length in both TEVAR and control patients increased at 0.58 mm/yr. Half of TEVAR patients had hypertension at follow-up compared to only 5% at baseline. CONCLUSIONS: TEVAR is associated with LV mass increase, development of hypertension, and accelerated expansile remodeling of the ascending aorta. Although younger trauma patients may adapt to these effects, these changes may be even more important in older patients with other aortic pathologies and diminished baseline cardiac function.

Mechanical and structural changes in human thoracic aortas with age.

Aortic mechanical and structural characteristics have profound effects on pathophysiology, but many aspects of physiologic stress-stretch state and intramural changes due to aging remain poorly understood in human tissues. While difficult to assess in vivo due to residual stresses and pre-stretch, physiologic stress-stretch characteristics can be calculated using experimentally-measured mechanical properties and constitutive modeling. Mechanical properties of 76 human descending thoracic aortas (TA) from 13 to 78-year-old donors (mean age 51±18 years) were measured using multi-ratio planar biaxial extension. Constitutive parameters were derived for aortas in 7 age groups, and the physiologic stress-stretch state was calculated. Intramural characteristics were quantified from histological images and related to aortic morphometry and mechanics. TA stiffness increased with age, and aortas became more nonlinear and anisotropic. Systolic and diastolic elastic energy available for pulsation decreased with age from 30 to 8 kPa and from 18 to 5 kPa, respectively. Cardiac cycle circumferential stretch dropped from 1.14 to 1.04, and circumferential and longitudinal physiologic stresses decreased with age from 90 to 72 kPa and from 90 to 17 kPa, respectively. Aortic wall thickness and radii increased with age, while the density of elastin in the tunica media decreased. The number of elastic lamellae and circumferential physiologic stress per lamellae unit remained constant with age at 102±10 and 0.85±0.04 kPa, respectively. Characterization of mechanical, physiological, and structural features in human aortas of different ages can help understand aortic pathology, inform the development of animal models that simulate human aging, and assist with designing devices for open and endovascular aortic repairs. STATEMENT OF SIGNIFICANCE: This manuscript describes mechanical and structural changes occurring in human thoracic aortas with age, and presents material parameters for 4 commonly used constitutive models. Presented data can help better understand aortic pathology, inform the development of animal models that simulate human aging, and assist with designing devices for open and endovascular aortic repairs.

Effects of longitudinal pre-stretch on the mechanics of human aorta before and after thoracic endovascular aortic repair (TEVAR) in trauma patients.

Thoracic endovascular aortic repair (TEVAR) has evolved as a first-line therapy for trauma patients. Most trauma patients are young, and their aortas are compliant and longitudinally pre-stretched. We have developed a method to include longitudinal pre-stretch in computational models of human thoracic aortas of different ages before and after TEVAR. Finite element models were built using computerized tomography angiography data obtained from human subjects in 6 age groups 10-69 years old. Aortic properties were determined with planar biaxial testing, and pre-stretch was simulated using a series of springs. GORE C-Tag stent-graft was computationally deployed in aortas with and without pre-stretch, and the stress-strain fields were compared. Pre-stretch had significant qualitative and quantitative effects on the aortic stress-strain state before and after TEVAR. Before TEVAR, mean intramural aortic stresses with and without pre-stretch decreased with age from 108 kPa and 83 kPa in the youngest age group, to 60 kPa in the oldest age group. TEVAR increased intramural stresses by an average of 73 ± 15 kPa and 48 ± 10 kPa for aortas with and without pre-stretch and produced high stress concentrations near the aortic isthmus. Inclusion of pre-stretch in young aortas increased intramural stresses by 30%, while in > 50-year-old subjects it did not change the results. Computational modeling of aorta-stent-graft interaction that includes pre-stretch can be instrumental for device design and assessment of its long-term performance, and in the future may help more accurately determine the stress-strain characteristics associated with TEVAR complications.

Mechanical stresses associated with flattening of human femoropopliteal artery specimens during planar biaxial testing and their effects on the calculated physiologic stress-stretch state.

Planar biaxial testing is commonly used to characterize the mechanical properties of arteries, but stresses associated with specimen flattening during this test are unknown. We quantified flattening effects in human femoropopliteal arteries (FPAs) of different ages and determined how they affect the calculated arterial physiologic stress-stretch state. Human FPAs from 472 tissue donors (age 12-82 years, mean 53 ± 16 years) were tested using planar biaxial extension, and morphometric and mechanical characteristics were used to assess the flattening effects. Constitutive parameters for the invariant-based model were adjusted to account for specimen flattening and used to calculate the physiologic stresses, stretches, axial force, circumferential stiffness, and stored energy for the FPAs in seven age groups. Flattened specimens were overall 12 ± 4% stiffer longitudinally and 19 ± 11% stiffer circumferentially when biaxially tested. Differences between the stress-stretch curves adjusted and non-adjusted for the effects of flattening were relatively constant across all age groups longitudinally, but increased with age circumferentially. In all age groups, these differences were smaller than the intersubject variability. Physiologic stresses, stretches, axial force, circumferential stiffness, and stored energy were all qualitatively and quantitatively similar when calculated with and without the flattening effects. Stresses, stretches, axial force, and stored energy reduced with age, but circumferential stiffness remained relatively constant between 25 and 65 years of age suggesting a homeostatic target of 0.75 ± 0.02 MPa. Flattening effects associated with planar biaxial testing are smaller than the intersubject variability and have little influence on the calculated physiologic stress-stretch state of human FPAs.

Mechanical damage characterization in human femoropopliteal arteries of different ages.

Endovascular treatment of Peripheral Arterial Disease (PAD) is notorious for high failure rates, and interaction between the arterial wall and the repair devices plays a significant role. Computational modeling can help improve clinical outcomes of these interventions, but it requires accurate inputs of elastic and damage characteristics of the femoropopliteal artery (FPA) which are currently not available. Fresh human FPAs from n = 104 tissue donors 14-80 years old were tested using planar biaxial extension to capture elastic and damage characteristics. Damage initiation stretches and stresses were determined for both longitudinal and circumferential directions, and their correlations with age and risk factors were assessed. Two and four-fiber-family invariant-based constitutive models augmented with damage functions were used to describe stress softening with accumulating damage. In FPAs younger than 50 years, damage began accumulating after 1.51 ±â€¯0.13 and 1.49 ±â€¯0.11 stretch, or 196 ±â€¯110 kPa and 239 ±â€¯79 kPa Cauchy stress in the longitudinal and circumferential directions, respectively. In FPAs older than 50 years, damage initiation stretches and stresses decreased to 1.27 ±â€¯0.09 (106 ±â€¯52 kPa) and 1.26 ±â€¯0.09 (104 ±â€¯59 kPa), respectively. Damage manifested primarily as tears at the internal and external elastic laminae and within the tunica media layer. Higher body mass index and presence of diabetes were associated with lower damage initiation stretches and higher stresses. The selected constitutive models were able to accurately portray the FPA behavior in both elastic and inelastic domains, and properties were derived for six age groups. Presented data can help improve fidelity of computational models simulating endovascular PAD repairs that involve arterial damage. STATEMENT OF SIGNIFICANCE: This manuscript describes inelastic, i.e. damage, behavior of human femoropopliteal arteries, and provides values for three constitutive models simulating this behavior computationally. Using a set of 104 human FPAs 14-80 years old, we have investigated stress and stretch levels corresponding to damage initiation, and have studied how these damage characteristics change across different age groups. Presented inelastic arterial characteristics are important for computational simulations modeling balloon angioplasty and stenting of peripheral arterial disease lesions.

Stent Design Affects Femoropopliteal Artery Deformation.

BACKGROUND: Poor durability of femoropopliteal artery (FPA) stenting is multifactorial, and severe FPA deformations occurring with limb flexion are likely involved. Different stent designs result in dissimilar stent-artery interactions, but the degree of these effects in the FPA is insufficiently understood. OBJECTIVES: To determine how different stent designs affect limb flexion-induced FPA deformations. METHODS: Retrievable markers were deployed into n = 28 FPAs of lightly embalmed human cadavers. Bodies were perfused and CT images were acquired with limbs in the standing, walking, sitting, and gardening postures. Image analysis allowed measurement of baseline FPA foreshortening, bending, and twisting associated with each posture. Markers were retrieved and 7 different stents were deployed across the adductor hiatus in the same limbs. Markers were then redeployed in the stented FPAs, and limbs were reimaged. Baseline and stented FPA deformations were compared to determine the influence of each stent design. RESULTS: Proximal to the stent, Innova, Supera, and SmartFlex exacerbated foreshortening, SmartFlex exacerbated twisting, and SmartControl restricted bending of the FPA. Within the stent, all devices except Viabahn restricted foreshortening; Supera, SmartControl, and AbsolutePro restricted twisting; SmartFlex and Innova exacerbated twisting; and Supera and Viabahn restricted bending. Distal to the stents, all devices except AbsolutePro and Innova exacerbated foreshortening, and Viabahn, Supera, Zilver, and SmartControl exacerbated twisting. All stents except Supera were pinched in flexed limb postures. CONCLUSIONS: Peripheral self-expanding stents significantly affect limb flexion-induced FPA deformations, but in different ways. Although certain designs seem to accommodate some deformation modes, no device was able to match all FPA deformations.

Cross-sectional pinching in human femoropopliteal arteries due to limb flexion, and stent design optimization for maximum cross-sectional opening and minimum intramural stresses.

High failure rates of femoropopliteal artery (FPA) interventions are often attributed to severe mechanical deformations that occur with limb flexion. One of these deformations, cross-sectional pinching, has a direct effect on blood flow, but is poorly characterized. Intra-arterial markers were deployed into n = 50 in situ cadaveric FPAs (80 ± 12 years old, 14F/11M), and limbs were imaged in standing, walking, sitting and gardening postures. Image analysis was used to measure marker openings and calculate FPA pinching. Parametric finite element analysis on a stent section was used to determine the optimal combination of stent strut amplitude, thickness and the number of struts per section to maximize cross-sectional opening and minimize intramural mechanical stress and low wall shear stress. Pinching was higher distally and increased with increasing limb flexion. In the walking, sitting and gardening postures, it was 1.16-1.24, 1.17-1.26 and 1.19-1.35, respectively. Stent strut amplitude and thickness had strong effects on both intramural stresses and pinching. Stents with a strut amplitude of 3 mm, thickness of 175 µm and 20 struts per section produced pinching and intramural stresses typical for a non-stented FPA, while also minimizing low wall shear stress areas, and ensuring a stent lifespan of at least 107 cycles. These results can help guide the development of improved devices and materials to treat peripheral arterial disease.

Nitinol Stents in the Femoropopliteal Artery: A Mechanical Perspective on Material, Design, and Performance.

Endovascular stenting has matured into a commonly used treatment for peripheral arterial disease (PAD) due to its minimally invasive nature and associated reductions in short-term morbidity and mortality. The mechanical properties of the superelastic Nitinol alloy have played a major role in the explosion of peripheral artery stenting, with modern stents demonstrating reasonable resilience and durability. Yet in the superficial femoral and popliteal arteries, even the newest generation Nitinol stents continue to demonstrate clinical outcomes that leave significant room for improvement. Restenosis and progression of native arterial disease often lead to recurrence of symptoms and reinterventions that increase morbidity and health care expenditures. One of the main factors thought to be associated with stent failure in the femoropopliteal artery (FPA) is the unique and highly dynamic mechanical environment of the lower limb. Clinical and experimental data demonstrate that the FPA undergoes significant deformations with limb flexion. It is hypothesized that the inability of many existing stent designs to conform to these deformations likely plays a role in reconstruction failure, as repetitive movements of the leg and thigh combine with mechanical mismatch between the artery and the stent and result in mechanical damage to both the artery and the stent. In this review we will identify challenges and provide a mechanical perspective of FPA stenting, and then discuss current research directions with promise to provide a better understanding of Nitinol, specific features of stent design, and improved characterization of the biomechanical environment of the FPA to facilitate development of better stents for patients with PAD.

Effect of aging on mechanical stresses, deformations, and hemodynamics in human femoropopliteal artery due to limb flexion.

Femoropopliteal artery (FPA) reconstructions are notorious for poor clinical outcomes. Mechanical and flow conditions that occur in the FPA with limb flexion are thought to play a significant role, but are poorly characterized. FPA deformations due to acute limb flexion were quantified using a human cadaver model and used to build a finite element model that simulated surrounding tissue forces associated with limb flexion-induced deformations. Strains and intramural principal mechanical stresses were determined for seven age groups. Computational fluid dynamics analysis was performed to assess hemodynamic variables. FPA shape, stresses, and hemodynamics significantly changed with age. Younger arteries assumed straighter positions in the flexed limb with less pronounced bends and more uniform stress distribution along the length of the artery. Even in the flexed limb posture, FPAs younger than 50 years of age experienced tension, while older FPAs experienced compression. Aging resulted in localization of principal mechanical stresses to the adductor hiatus and popliteal artery below the knee that are typically prone to developing vascular pathology. Maximum principal stresses in these areas increased threefold to fivefold with age with largest increase observed at the adductor hiatus. Atheroprotective wall shear stress reduced after 35 years of age, and atheroprone and oscillatory shear stresses increased after the age of 50. These data can help better understand FPA pathophysiology and can inform the design of targeted materials and devices for peripheral arterial disease treatments.

Constitutive modeling of human femoropopliteal artery biaxial stiffening due to aging and diabetes.

Atherosclerotic obstructive disease of the femoropopliteal artery (Peripheral Arterial Disease, PAD) is notorious for high treatment failure rates. Older age and diabetes mellitus (DM) are among the major risk factors for PAD, and both are associated with increased arterial stiffness. Our goal was to develop a constitutive model describing multiaxial arterial stiffening, and use it to portray aging of normal and diabetic human femoropopliteal arteries (FPA). Fresh human FPAs (n=744) were obtained from 13-82-year-old donors. Arteries were tested using planar biaxial extension, and their behavior was modeled with a constitutive relation that included stiffening functions of age. FPA diameter, wall thickness, circumferential, and longitudinal opening angles increased with age, while longitudinal pre-stretch decreased. Diameter and circumferential opening angle did not change with age in subjects with DM. Younger FPAs were more compliant longitudinally but became more isotropic with age. Arteries with DM stiffened significantly faster in the circumferential direction than arteries without DM. Constitutive model accurately portrayed orthotropic stiffening with age of both normal and diabetic arteries. Constitutive description of FPA aging contributes to understanding of arterial pathophysiology and can help improve fidelity of computational models investigating device-artery interaction in PAD repair by providing more personalized arterial properties. STATEMENT OF SIGNIFICANCE: We have analyzed n=744 human femoropopliteal artery (FPA) specimens using biaxial tensile testing to derive constitutive description of FPA aging in diabetic and non-diabetic subjects. The proposed model allows determination of FPA mechanical properties for subjects of any given age in the range of 13-82years. These results contribute to understanding of FPA pathophysiology and can help improve fidelity of computational models investigating device-artery interaction in peripheral arterial disease repair by providing more personalized arterial properties. In addition, they can guide the development of new materials tunable to diabetic and non-diabetic arteries.

Comparison of femoropopliteal artery stents under axial and radial compression, axial tension, bending, and torsion deformations.

High failure rates of Peripheral Arterial Disease (PAD) stenting appear to be associated with the inability of certain stent designs to accommodate severe biomechanical environment of the femoropopliteal artery (FPA) that bends, twists, and axially compresses during limb flexion. Twelve Nitinol stents (Absolute Pro, Supera, Lifestent, Innova, Zilver, Smart Control, Smart Flex, EverFlex, Viabahn, Tigris, Misago, and Complete SE) were quasi-statically tested under bench-top axial and radial compression, axial tension, bending, and torsional deformations. Stents were compared in terms of force-strain behavior, stiffness, and geometrical shape under each deformation mode. Tigris was the least stiff stent under axial compression (6.6N/m axial stiffness) and bending (0.1N/m) deformations, while Smart Control was the stiffest (575.3N/m and 105.4N/m, respectively). Under radial compression Complete SE was the stiffest (892.8N/m), while Smart Control had the lowest radial stiffness (211.0N/m). Viabahn and Supera had the lowest and highest torsional stiffness (2.2µNm/° and 959.2µNm/°), respectively. None of the 12 PAD stents demonstrated superior characteristics under all deformation modes and many experienced global buckling and diameter pinching. Though it is yet to be determined which of these deformation modes might have greater clinical impact, results of the current analysis may help guide development of new stents with improved mechanical characteristics.

Limb flexion-induced twist and associated intramural stresses in the human femoropopliteal artery.

High failure rates of femoropopliteal artery (FPA) interventions are often attributed to severe mechanical deformations that occur with limb movement. Torsion of the FPA likely plays a significant role, but is poorly characterized and the associated intramural stresses are currently unknown. FPA torsion in the walking, sitting and gardening postures was characterized in n = 28 in situ FPAs using intra-arterial markers. Principal mechanical stresses and strains were quantified in the superficial femoral artery (SFA), adductor hiatus segment (AH) and the popliteal artery (PA) using analytical modelling. The FPA experienced significant torsion during limb flexion that was most severe in the gardening posture. The associated mechanical stresses were non-uniformly distributed along the length of the artery, increasing distally and achieving maximum values in the PA. Maximum twist in the SFA ranged 10-13° cm-1, at the AH 8-16° cm-1, and in the PA 14-26° cm-1 in the walking, sitting and gardening postures. Maximum principal stresses were 30-35 kPa in the SFA, 27-37 kPa at the AH and 39-43 kPa in the PA. Understanding torsional deformations and intramural stresses in the FPA can assist with device selection for peripheral arterial disease interventions and may help guide the development of devices with improved characteristics.

Constitutive description of human femoropopliteal artery aging.

Femoropopliteal artery (FPA) mechanics play a paramount role in pathophysiology and the artery's response to therapeutic interventions, but data on FPA mechanical properties are scarce. Our goal was to characterize human FPAs over a wide population to derive a constitutive description of FPA aging to be used for computational modeling. Fresh human FPA specimens ([Formula: see text]) were obtained from [Formula: see text] predominantly male (80 %) donors 54±15 years old (range 13-82 years). Morphometric characteristics including radius, wall thickness, opening angle, and longitudinal pre-stretch were recorded. Arteries were subjected to multi-ratio planar biaxial extension to determine constitutive parameters for an invariant-based model accounting for the passive contributions of ground substance, elastin, collagen, and smooth muscle. Nonparametric bootstrapping was used to determine unique sets of material parameters that were used to derive age-group-specific characteristics. Physiologic stress-stretch state was calculated to capture changes with aging. Morphometric and constitutive parameters were derived for seven age groups. Vessel radius, wall thickness, and circumferential opening angle increased with aging, while longitudinal pre-stretch decreased ([Formula: see text]). Age-group-specific constitutive parameters portrayed orthotropic FPA stiffening, especially in the longitudinal direction. Structural changes in artery wall elastin were associated with reduction of physiologic longitudinal and circumferential stretches and stresses with age. These data and the constitutive description of FPA aging shed new light on our understanding of peripheral arterial disease pathophysiology and arterial aging. Application of this knowledge might improve patient selection for specific treatment modalities in personalized, precision medicine algorithms and could assist in device development for treatment of peripheral artery disease.

The choice of a constitutive formulation for modeling limb flexion-induced deformations and stresses in the human femoropopliteal arteries of different ages.

Open and endovascular treatments for peripheral arterial disease are notorious for high failure rates. Severe mechanical deformations experienced by the femoropopliteal artery (FPA) during limb flexion and interactions between the artery and repair materials play important roles and may contribute to poor clinical outcomes. Computational modeling can help optimize FPA repair, but these simulations heavily depend on the choice of constitutive model describing the arterial behavior. In this study finite element model of the FPA in the standing (straight) and gardening (acutely bent) postures was built using computed tomography data, longitudinal pre-stretch and biaxially determined mechanical properties. Springs and dashpots were used to represent surrounding tissue forces associated with limb flexion-induced deformations. These forces were then used with age-specific longitudinal pre-stretch and mechanical properties to obtain deformed FPA configurations for seven age groups. Four commonly used invariant-based constitutive models were compared to determine the accuracy of capturing deformations and stresses in each age group. The four-fiber FPA model most accurately portrayed arterial behavior in all ages, but in subjects younger than 40 years, the performance of all constitutive formulations was similar. In older subjects, Demiray (Delfino) and classic two-fiber Holzapfel-Gasser-Ogden formulations were better than the Neo-Hookean model for predicting deformations due to limb flexion, but both significantly overestimated principal stresses compared to the FPA or Neo-Hookean models.

Morphometric roadmaps to improve accurate device delivery for fluoroscopy-free resuscitative endovascular balloon occlusion of the aorta.

BACKGROUND: Uncontrolled hemorrhage from vessel injuries within the torso remains a significant source of prehospital trauma mortality. Resuscitative endovascular balloon occlusion of the aorta can effectively control noncompressible hemorrhage, but this minimally invasive technique relies heavily on imaging not available in the field. Our goal was to develop morphometric roadmaps to enhance the safety and accuracy of fluoroscopy-free endovascular navigation of hemorrhage control devices. METHODS: Three-dimensional reconstructions of computed tomographic angiography scans from 122 trauma patients (mean [SD] age, 47 [24] years; range 5-93 years; 64 males; 58 females) were used to measure centerline distances from femoral artery access sites to the major aortic branch artery origins. Morphometric roadmap equations were created using multiple linear regression analysis to predict distances to the origins of the major arteries in the chest, abdomen, and pelvis using torso length, demographics, and risk factors as independent variables. A 40-mm-long occlusion balloon was then virtually deployed targeting Zones 1 and 3 of the aorta using these equations. Balloon placement accuracy was determined by comparing predicted versus actual measured distances to the target zone locations within the aortas from the database. RESULTS: Torso length and age were the strongest predictors of centerline distances from femoral artery access sites to the major artery origins. Male sex contributed to longer distances, while diabetes and smoking were associated with shorter distances. Hypertension, dyslipidemia, and coronary artery disease had no effect. With the use of morphometric roadmaps, virtual occlusion balloon placement accuracy was 100% for Zone 3 of the aorta, compared with 87% accuracy when using torso length alone. CONCLUSION: Morphometric roadmaps demonstrate a potential for improving the safety and accuracy of fluoroscopy-free aortic occlusion balloon delivery. Continued development of minimally invasive hemorrhage control techniques holds promise to improve prehospital mortality for patients with noncompressible exsanguinating torso injuries. LEVEL OF EVIDENCE: Therapeutic study, level IV; diagnostic study, level III.

In situ longitudinal pre-stretch in the human femoropopliteal artery.

In situ longitudinal (axial) pre-stretch (LPS) plays a fundamental role in the mechanics of the femoropopliteal artery (FPA). It conserves energy during pulsation and prevents buckling of the artery during limb movement. We investigated how LPS is affected by demographics and risk factors, and how these patient characteristics associate with the structural and physiologic features of the FPA. LPS was measured in n=148 fresh human FPAs (14-80 years old). Mechanical properties were characterized with biaxial extension and histopathological characteristics were quantified with Verhoeff-Van Gieson Staining. Constitutive modeling was used to calculate physiological stresses and stretches which were then analyzed in the context of demographics, risk factors and structural characteristics. Age had the strongest negative effect (r=-0.812, p<0.01) on LPS and could alone explain 66% of LPS variability. Male gender, higher body mass index, hypertension, diabetes, coronary artery disease, dyslipidemia and tobacco use had negative effects on LPS, but only the effect of tobacco was not associated with aging. FPAs with less pre-stretch had thicker medial layers, but thinner intramural elastic fibers with less dense and more fragmented external elastic laminae. Elastin degradation was associated with decreased physiological tethering force and longitudinal stress, while circumferential stress remained constant. FPA wall pathology was negatively associated with LPS (r=-0.553, p<0.01), but the effect was due primarily to aging. LPS in the FPA may serve as an energy reserve for adaptive remodeling. Reduction of LPS due to degradation and fragmentation of intramural longitudinal elastin during aging can be accelerated in tobacco users. STATEMENT OF SIGNIFICANCE: This work studies in situ longitudinal pre-stretch (LPS) in the human femoropopliteal artery. LPS has a fundamental role in arterial mechanics, but is rather poorly studied due to lack of direct in vivo measurement method. We have investigated LPS in the n=148 human femoropopliteal arteries in the context of subject demographics and risk factors, and structural and physiologic characteristics of the artery. Our results demonstrate that LPS reduces with age due to degradation and fragmentation of intramural elastin. LPS may serve as an energy reserve for adaptive remodeling, and reduction of LPS can be accelerated in tobacco users.