The Effect of Collagenase on the Critical Buckling Pressure of Arteries^*

The stability of arteries is essential to normal arterial functions and loss of stability can lead to arterial tortuosity and kinking. Collagen is a main extracellular matrix component that modulates the mechanical properties of arteries and collagen degradation at pathological conditions weakens the mechanical strength of arteries. However, the effects of collagen degradation on the mechanical stability of arteries are unclear. The objective of this study was to investigate the effects of collagen degradation on the critical buckling pressure of arteries. Arterial specimens were subjected to pressurized inflation testing and fitted with nonlinear thick-walled cylindrical model equations to determine their stress strain relationships. The arteries were then tested for the critical buckling pressure at a set of axial stretch ratios. Then, arteries were divided into three groups and treated with Type III collagenase at three different concentrations (64, 128, and 400U/ml). Mechanical properties and buckling pressures of the arteries were determined after collagenase treatment. Additionally, the theoretical buckling pressures were also determined using a buckling equation. Our results demonstrated that the buckling pressure of arteries was lower after collagenase treatment. The difference between pre- and post- treatment was statistically significant for the highest concentration of 400U/ml but not at the lower concentrations. The buckling equation was found to yield a fair estimation to the experimental critical pressure measurements. These results shed light on the role of matrix remodeling on the mechanical stability of arteries and developments of tortuous arteries.     

The effect of collagenase on the critical buckling pressure of arteries

The stability of arteries is essential to normal arterial functions and loss of stability can lead to arterial tortuosity and kinking. Collagen is a main extracellular matrix component that modulates the mechanical properties of arteries and collagen degradation at pathological conditions weakens the mechanical strength of arteries. However, the effects of collagen degradation on the mechanical stability of arteries are unclear. The objective of this study was to investigate the effects of collagen degradation on the critical buckling pressure of arteries. Arterial specimens were subjected to pressurized inflation testing and fitted with nonlinear thick-walled cylindrical model equations to determine their stress strain relationships. The arteries were then tested for the critical buckling pressure at a set of axial stretch ratios. Then, arteries were divided into three groups and treated with Type III collagenase at three different concentrations (64, 128, and 400 U/ml). Mechanical properties and buckling pressures of the arteries were determined after collagenase treatment. Additionally, the theoretical buckling pressures were also determined using a buckling equation. Our results demonstrated that the buckling pressure of arteries was lower after collagenase treatment. The difference between pre- and post- treatment was statistically significant for the highest concentration of 400U/ml but not at the lower concentrations. The buckling equation was found to yield a fair estimation to the experimental critical pressure measurements. These results shed light on the role of matrix remodeling on the mechanical stability of arteries and developments of tortuous arteries.     

Blood vessel buckling within soft surrounding tissue generates tortuosity

The stability of blood vessel under lumen pressure load is essential to the maintenance of normal arterial function. Previous mechanical models showed that blood vessels may buckle into a half sine wave but arteries and veins in vivo often demonstrate tortuous paths with multiple waves. The objective of this study was to analyze the buckling of blood vessels under lumen pressure with surrounding tissue support. Blood vessels were modeled as elastic cylindrical vessels within an elastic substrate. Buckling equations were established to determine the critical pressure and the wavelength. These equations and simulation results demonstrated that blood vessels do take higher order mode shapes when buckling inside an elastic substrate while they take the basal mode shape without the substrate. The wave number increases i.e. blood vessels take a higher mode shape, as the stiffness of the substrate increases. These results suggest that mechanical buckling is a possible mechanism for the development of tortuous blood vessels. The current model provides a powerful tool for further studying the tortuosity of arteries and veins.     

Mechanical buckling of artery under pulsatile pressure

Tortuosity that often occurs in carotid and other arteries has been shown to be associated with high blood pressure, atherosclerosis, and other diseases. However the mechanisms of tortuosity development are not clear. Our previous studies have suggested that arteries buckling could be a possible mechanism for the initiation of tortuous shape but artery buckling under pulsatile flow condition has not been fully studied. The objectives of this study were to determine the artery critical buckling pressure under pulsatile pressure both experimentally and theoretically, and to elucidate the relationship of critical pressures under pulsatile flow, steady flow, and static pressure. We first tested the buckling pressures of porcine carotid arteries under these loading conditions, and then proposed a nonlinear elastic artery model to examine the buckling pressures under pulsatile pressure conditions. Experimental results showed that under pulsatile pressure arteries buckled when the peak pressures were approximately equal to the critical buckling pressures under static pressure. This was also confirmed by model simulations at low pulse frequencies. Our results provide an effective tool to predict artery buckling pressure under pulsatile pressure.     

Artery buckling analysis using a four-fiber wall model

Artery bent buckling has been suggested as a possible mechanism that leads to artery tortuosity, which is associated with aging, hypertension, atherosclerosis, and other pathological conditions. It is necessary to understand the relationship between microscopic wall structural changes and macroscopic artery buckling behavior. To this end, the objectives of this study were to develop arterial buckling equations using a microstructure-based 4-fiber reinforced wall model, and to simulate the effects of vessel wall microstructural changes on artery buckling. Our results showed that the critical pressure increased nonlinearly with the axial stretch ratio, and the 4-fiber model predicted higher critical buckling pressures than what the Fung model predicted. The buckling equation using the 4-fiber model captured the experimentally observed reduction of critical pressure induced by elastin degradation and collagen fiber orientation changes in the arterial wall. These results improve our understanding of arterial stability and its relationship to microscopic wall remodeling, and the model provides a useful tool for further studies.     

Mechanical instability of normal and aneurysmal arteries

Tortuous arteries associated with aneurysms have been observed in aged patients with atherosclerosis and hypertension. However, the underlying mechanism is poorly understood. The objective of this study was to determine the effect of aneurysms on arterial buckling instability and the effect of buckling on aneurysm wall stress. We investigated the mechanical buckling and post-buckling behavior of normal and aneurysmal carotid arteries and aorta’s using computational simulations and experimental measurements to elucidate the interrelationship between artery buckling and aneurysms. Buckling tests were done in porcine carotid arteries with small aneurysms created using elastase treatment. Parametric studies were done for model aneurysms with orthotropic nonlinear elastic walls using finite element simulations. Our results demonstrated that arteries buckled at a critical buckling pressure and the post-buckling deflection increased nonlinearly with increasing pressure. The presence of an aneurysm can reduce the critical buckling pressure of arteries, although the effect depends on the aneurysm’s dimensions. Buckled aneurysms demonstrated a higher peak wall stress compared to unbuckled aneurysms under the same lumen pressure. We conclude that aneurysmal arteries are vulnerable to mechanical buckling and mechanical buckling could lead to high stresses in the aneurysm wall. Buckling could be a possible mechanism for the development of tortuous aneurysmal arteries such as in the Loeys–Dietz syndrome.     

Heightened aberrant deposition of hard-wearing elastin in conduit arteries of prehypertensive SHR is associated with increased stiffness and inward remodeling

Elastin is a major component of conduit arteries and a key determinant of vascular viscoelastic properties. Aberrant organization of elastic lamellae has been reported in resistance vessels from spontaneously hypertensive rats (SHR) before the development of hypertension. Hence, we have characterized the content and organization of elastic lamellae in conduit vessels of neonatal SHR in detail, comparing the carotid arteries from 1-wk-old SHR with those from Wistar-Kyoto (WKY) and Sprague Dawley (SD) rats. The general structure and mechanics were studied by pressure myography, and the internal elastic lamina organization was determined by confocal microscopy. Cyanide bromide-insoluble elastin scaffolds were also prepared from 1-mo-old SHR and WKY aortas to assess their weight, amino acid composition, three-dimensional lamellar organization, and mechanical characteristics. Carotid arteries from 1-wk-old SHR exhibited narrower lumen and greater intrinsic stiffness than those from their WKY and SD counterparts. These aberrations were associated with heightened elastin content and with a striking reduction in the size of the fenestrae present in the elastic lamellae. The elastin scaffolds isolated from SHR aortas also exhibited increased relative weight and stiffness, as well as the presence of peculiar trabeculae inside the fenestra that reduced their size. We suggest that the excessive and aberrant elastin deposited in SHR vessels during perinatal development alters their mechanical properties. Such abnormalities are likely to compromise vessel expansion during a critical period of growth and, at later stages, they could compromise hemodynamic function and participate in the development of systemic hypertension.     

The Effect of Static Stretch on Elastin Degradation in Arteries

Previously we have shown that gradual changes in the structure of elastin during an elastase treatment can lead to important transition stages in the mechanical behavior of arteries [1]. However, in vivo arteries are constantly being loaded due to systolic and diastolic pressures and so understanding the effects of loading on the enzymatic degradation of elastin in arteries is important. With biaxial tensile testing, we measured the mechanical behavior of porcine thoracic aortas digested with a mild solution of purified elastase (5 U/mL) in the presence of a static stretch. Arterial mechanical properties and biochemical composition were analyzed to assess the effects of mechanical stretch on elastin degradation. As elastin is being removed, the dimensions of the artery increase by more than 20% in both the longitude and circumference directions. Elastin assays indicate a faster rate of degradation when stretch was present during the digestion. A simple exponential decay fitting confirms the time constant for digestion with stretch (0.11±0.04 h⁻¹) is almost twice that of digestion without stretch (0.069±0.028 h⁻¹). The transition from J-shaped to S-shaped stress vs. strain behavior in the longitudinal direction generally occurs when elastin content is reduced by about 60%. Multiphoton image analysis confirms the removal/fragmentation of elastin and also shows that the collagen fibers are closely intertwined with the elastin lamellae in the medial layer. After removal of elastin, the collagen fibers are no longer constrained and become disordered. Release of amorphous elastin during the fragmentation of the lamellae layers is observed and provides insights into the process of elastin degradation. Overall this study reveals several interesting microstructural changes in the extracellular matrix that could explain the resulting mechanical behavior of arteries with elastin degradation.     

Compromised mechanical homeostasis in arterial aging and associated cardiovascular consequences

Aging leads to central artery stiffening and associated hemodynamic sequelae. Because healthy arteries exhibit differential geometry, composition, and mechanical behaviors along the central vasculature, we sought to determine whether wall structure and mechanical function differ across five vascular regions—the ascending and descending thoracic aorta, suprarenal and infrarenal abdominal aorta, and common carotid artery—in 20 versus 100-week-old male wild-type mice. Notwithstanding generally consistent changes across these regions, including a marked thickening of the arterial wall, diminished in vivo axial stretch, and loss of elastic energy storage capacity, the degree of changes tended to be slightly greater in abdominal than in thoracic or carotid vessels. Likely due to the long half-life of vascular elastin, most mechanical changes in the arterial wall resulted largely from a distributed increase in collagen, including thicker fibers in the media, and localized increases in glycosaminoglycans. Changes within the central arteries associated with significant increases in central pulse pressure and adverse changes in the left ventricle, including increased cardiac mass and decreased diastolic function. Given the similar half-life of vascular elastin in mice and humans but very different life-spans, there are important differences in the aging of central vessels across these species. Nevertheless, the common finding of aberrant matrix remodeling contributing to a compromised mechanical homeostasis suggests that studies of central artery aging in the mouse can provide insight into mechanisms and treatment strategies for the many adverse effects of vascular aging in humans.     

Twist buckling behavior of arteries

Arteries are often subjected to torsion due to body movement and surgical procedures. While it is essential that arteries remain stable and patent under twisting loads, the stability of arteries under torsion is poorly understood. The goal of this work was to experimentally investigate the buckling behavior of arteries under torsion and to determine the critical buckling torque, the critical buckling twist angle, and the buckling shape. Porcine common carotid arteries were slowly twisted in vitro until buckling occurred while subjected to a constant axial stretch ratio (1.1, 1.3, 1.5 (in vivo level) and 1.7) and lumen pressure (20, 40, 70 and 100 mmHg). Upon buckling, the arteries snapped to form a kink. For a group of six arteries, the axial stretch ratio significantly affected the critical buckling torque (\(p<0.002\)) and the critical buckling twist angle (\(p<0.001\)). Lumen pressure also significantly affected the critical buckling torque (\(p<0.001\)) but had no significant effect on the critical twist angle (\(p=0.067\)). Convex material constants for a Fung strain energy function were determined and fit well with the axial force, lumen pressure, and torque data measured pre-buckling. The material constants are valid for axial stretch ratios, lumen pressures, and rotation angles of 1.3–1.5, 20–100 mmHg, and 0–270\(^\circ \), respectively. The current study elucidates the buckling behavior of arteries under torsion and provides new insight into mechanical instability of blood vessels.     

A biomechanical model of artery buckling

The stability of arteries under blood pressure load is essential to the maintenance of normal arterial function and the loss of stability can lead to tortuosity and kinking that are associated with significant clinical complications. However, mechanical analysis of arterial bent buckling is lacking. To address this issue, this paper presents a biomechanical model of arterial buckling. Using an elastic cylindrical arterial model, the mechanical equations for arterial buckling were developed and the critical buckling pressure was found to be a function of the wall stiffness (Young's modulus), arterial radius, length, wall thickness, and the axial strain. Both the model equations and experimental results demonstrated that the critical pressure is related to the axial strain. Arteries may buckle and become tortuous due to reduced (subphysiological) axial strain, hypertensive pressure, and a weakened wall. These results are in accordance with, and provide a possible explanation to the clinical observations that hypertension and aging are the risk factors for arterial tortuosity and kinking. The current model is also applicable to veins and ureters.     

Responses of vascular smooth muscle cell to extracellular matrix degradation.

Vessels remodel to compensate for increases in blood flow/pressure. The chronic exposure of blood vessels to increased flow and circulatory redox-homocysteine may injure vascular endothelium and disrupt elastic laminae. In order to understand the role of extracellular matrix (ECM) degradation in vascular structure and function, we isolated human vascular smooth muscle cells (VSMC) from normal and injured coronary arteries. The apparently normal vessels were isolated from explanted human hearts. The vessels were injured by inserting a blade into the lumen of the vessel, which damages the inner elastic laminae in the vessel wall and polarizes the VSMC by producing a pseudopodial phenotypic shift in VSMC. This shift is characteristic of migratory, invasive, and contractile nature of VSMC. We measured extracellular matrix metalloproteinases (MMPs), tissue plasminogen activator (tPA), tissue inhibitor of metalloproteinase (TIMP), and collagen I expression in VSMC by specific substrate zymography and Northern blot analyses. The injured and elastin peptide, val-gly-val-ala-pro-gly, treated VSMC synthesized active MMPs and reduced expression of TIMP. The level of tPA and collagen type I was induced in the injured, invasive VSMC and in the val-gly-val-ala-pro-gly treated cells. To demonstrate the angiogenic role of elastin peptide to VSMC we performed in vitro organ culture with rings from normal coronary artery. After 3 days in culture the vascular rings in the collagen gel containing elastin peptide elaborated MMP activity and sprouted and grew. The results suggest that val-gly-val-ala-pro-gly peptide generated at the site of proteolysis during vascular injury may have angiogenic activity.     

Contribution of elastin and collagen to the inflation response of the pig thoracic aorta: assessing elastin's role in mechanical homeostasis

This study was undertaken to understand elastin's role in the mechanical homeostasis of the arterial wall. The mechanical properties of elastin vary along the aorta, and we hypothesized this maintained a uniform mechanical environment for the elastin, despite regional variation in loading. Elastin's physiological loading was determined by comparing the inflation response of intact and autoclave purified elastin aortas from the proximal and distal thoracic aorta. Elastin's stretch and stress depend on collagen recruitment. Collagen recruitment started in the proximal aorta at systolic pressures (13.3 to 14.6 kPa) and in the distal at sub-diastolic pressures (9.3 to 10.6 kPa). In the proximal aorta collagen did not contribute significantly to the stress or stiffness, indicating that elastin determined the vessel properties. In the distal aorta, the circumferential incremental modulus was 70% higher than in the proximal aorta, half of which (37%) was due to a stiffening of the elastin. Compared to the elastin tissue in the proximal aorta, the distal elastin suffered higher physiological circumferential stretch (29%, P=0.03), circumferential stress (39%, P=0.02), and circumferential stiffness (37%, P=0.006). Elastin's physiological axial stresses were also higher (67%, P=0.003). These findings do not support the hypothesis that the loading on elastin is constant along the aorta as we expected from homeostasis.     

Fluid-structure interaction modeling of aneurysmal arteries under steady-state and pulsatile blood flow: a stability analysis

Tortuous aneurysmal arteries are often associated with a higher risk of rupture but the mechanism remains unclear. The goal of this study was to analyze the buckling and post-buckling behaviors of aneurysmal arteries under pulsatile flow. To accomplish this goal, we analyzed the buckling behavior of model carotid and abdominal aorta with aneurysms by utilizing fluid-structure interaction (FSI) method with realistic waveforms boundary conditions. FSI simulations were done under steady-state and pulsatile flow for normal (1.5) and reduced (1.3) axial stretch ratios to investigate the influence of aneurysm, pulsatile lumen pressure and axial tension on stability. Our results indicated that aneurysmal artery buckled at the critical buckling pressure and its deflection nonlinearly increased with increasing lumen pressure. Buckling elevates the peak stress (up to 118%). The maximum aneurysm wall stress at pulsatile FSI flow was (29%) higher than under static pressure at the peak lumen pressure of 130 mmHg. Buckling results show an increase in lumen shear stress at the inner side of the maximum deflection. Vortex flow was dramatically enlarged with increasing lumen pressure and artery diameter. Aneurysmal arteries are more susceptible than normal arteries to mechanical instability which causes high stresses in the aneurysm wall that could lead to aneurysm rupture.     

Surrounding tissues affect the passive mechanics of the vessel wall: theory and experiment

The stress and strain in the vessel wall are important determinants of vascular physiology and pathophysiology. Vessels are constrained radially by the surrounding tissue. The hypothesis in this work is that the surrounding tissue takes up a considerable portion of the intravascular pressure and significantly reduces the wall strain and stress. Ten swine of either sex were used to test this hypothesis. An impedance catheter was inserted into the carotid or femoral artery, and after mechanical preconditioning pressure-cross-sectional area relations were obtained with the surrounding tissue intact and dissected away (untethered), respectively. The radial constraint of the surrounding tissue was quantified as an effective perivascular pressure on the outer surface of the vessel, which was estimated as 50% or more of the intravascular pressure. For carotid arteries at pressure of 100 mmHg, the circumferential wall stretch ratio in the intact state was approximately 20% lower than in the untethered state and the average circumferential stress was reduced by approximately 70%. For femoral arteries, the reductions were approximately 15% and 70%, respectively. These experimental data support the proposed hypothesis and suggest that in vitro and in vivo measurements of the mechanical properties of vessels must be interpreted with consideration of the constraint of the surrounding tissue.     

Mechanics of the human femoral adventitia including the high-pressure response

Adventitial mechanics were studied on the basis of adventitial tube tests and associated stress analyses utilizing a thin-walled model. Inflation tests of 11 nonstenotic human femoral arteries (79.3 +/- 8.2 yr, means +/- SD) were performed during autopsy. Adventitial tubes were separated anatomically and underwent cyclic, quasistatic extension-inflation tests using physiological pressures and high pressures up to 100 kPa. Associated circumferential and axial stretches were typically <20%, indicating "adventitiosclerosis." Adventitias behaved nearly elastically for both loading domains, demonstrating high tensile strengths (>1 MPa). The anisotropic and strongly nonlinear mechanical responses were represented appropriately by two-dimensional Fung-type stored-energy functions. At physiological pressure (13.3 kPa), adventitias carry ~25% of the pressure load in situ, whereas their circumferential and axial stresses were similar to the total wall stresses (~50 kPa in both directions), supporting a "uniform stress hypothesis." At higher pressures, they became the mechanically predominant layer, carrying >50% of the pressure load. These significant load-carrying capabilities depended strongly on circumferential and axial in-vessel prestretches (mean values: 0.95 and 1.08). On the basis of these results, the mechanical role of the adventitia at physiological and hypertensive states and during balloon angioplasty was characterized.     

Artery buckling affects the mechanical stress in atherosclerotic plaques

Background

Tortuous arteries are often seen in patients with hypertension and atherosclerosis. While the mechanical stress in atherosclerotic plaque under lumen pressure has been studied extensively, the mechanical stability of atherosclerotic arteries and subsequent effect on the plaque stress remain unknown. To this end, we investigated the buckling and post-buckling behavior of model stenotic coronary arteries with symmetric and asymmetric plaque.

Methods

Buckling analysis for a model coronary artery with symmetric and asymmetric plaque was conducted using finite element analysis based on the dimensions and nonlinear anisotropic materials properties reported in the literature.

Results

Artery with asymmetric plaque had lower critical buckling pressure compared to the artery with symmetric plaque and control artery. Buckling increased the peak stress in the plaque and led to the development of a high stress concentration in artery with asymmetric plaque. Stiffer calcified tissue and severe stenosis increased the critical buckling pressure of the artery with asymmetric plaque.

Conclusions

Arteries with atherosclerotic plaques are prone to mechanical buckling which leads to a high stress concentration in the plaques that can possibly make the plaques prone to rupture.

     

Effects of hydrogen sulfide on hypoxic pulmonary vascular structural remodeling

To study the role of hydrogen sulfide (H2S) in hypoxic pulmonary vascular structural remodeling (HPVSR), a total of 24 Wistar rats were randomly divided into three groups: control group (n = 8), hypoxia group (n = 8) and hypoxia with sodium hydrosulfide (hy + NaHS) group (n = 8). The mean pulmonary artery pressure (mPAP), plasma H2S and the percentage of muscularized arteries (MA), partially muscularized arteries (PMA) and nonmuscularized arteries (NMA) in small pulmonary vessels were measured. Collagen I and III, elastin, transforming growth factor-beta3 (TGF-beta3), proliferative cell nuclear antigen (PCNA) and human urotensin II(U-II) expressions were detected by immunohistochemical assay. The mRNA expressions of procollagen I and III, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinease-1 (TIMP-1) were detected by in situ hybridization. The results showed that NaHS significantly increased plasma H2S, decreased mPAP and the percentage of MA and PMA of small pulmonary vessels in rats under hypoxia. Meanwhile, NaHS inhibited the proliferation of pulmonary artery smooth muscle cells (PASMCs) represented by a decrease in the expressions of PCNA and human U-II in pulmonary artery wall. NaHS reduced the expression of collagen I and III, elastin and TGF-beta3 protein and decreased the expressions of procollagen I and III mRNA in pulmonary arteries of rats under hypoxia, but it did not impact the ratio of TIMP-1 mRNA to MMP-1mRNA in pulmonary arteries of rats under hypoxia. These data suggested that H2S played an important role in the development of HPVSR.     

Progressive structural and biomechanical changes in elastin degraded aorta

Aortic aneurysm is an important clinical condition characterized by common structural changes such as the degradation of elastin, loss of smooth muscle cells, and increased deposition of fibrillary collagen. With the goal of investigating the relationship between the mechanical behavior and the structural/biochemical composition of an artery, this study used a simple chemical degradation model of aneurysm and investigated the progressive changes in mechanical properties. Porcine thoracic aortas were digested in a mild solution of purified elastase (5 U/mL) for 6, 12, 24, 48, and 96 h. Initial size measurements show that disruption of the elastin structure leads to increased artery dilation in the absence of periodic loading. The mechanical properties of the digested arteries, measured with a biaxial tensile testing device, progress through four distinct stages termed (1) initial-softening, (2) elastomer-like, (3) extensible-but-stiff, and (4) collagen-scaffold-like. While stages 1, 3, and 4 are expected as a result of elastin degradation, the S-shaped stress versus strain behavior of the aorta resulting from enzyme digestion has not been reported previously. Our results suggest that gradual changes in the structure of elastin in the artery can lead to a progression through different mechanical properties and thus reveal the potential existence of an important transition stage that could contribute to artery dilation during aneurysm formation.     

The canine tail artery as a model for cerebral aneurysm studies

The occluded canine tail artery, which comes off in the same plane as the aortoiliac junction, has been used as a flow model for cerebral aneurysms. These experiments were designed to determine if it is a realistic distensible model of human intracranial aneurysms. Distensibility studies were done on the aorta, and the iliac and tail arteries of four dogs. From these pressure-volume studies, tension-strain curves, elastances, and collagen slack were obtained. The tail artery is stiffer longitudinally and more distensible circumferentially than the other vessels. The iliac arteries and the aorta are not significantly different. The elastance of elastin and collagen is lower in the tail artery, and the collagen is more wavy circumferentially. Longitudinally, the collagen slack is least for the tail artery, and the elastance of elastin is not different in all three vessels. The number of elastin layers in the iliac and tail arteries seen in cross section is not significantly different, but the aorta is different from both these vessels. In another four dogs the aorta proximal to the trifurcation was cannulated and infused with saline to increase pressure. India ink marks were put on the surface to measure changes in length. Photographs were taken at intervals of 10 mmHg(1 mmHg = 133.3 Pa). This was done with the vessels tethered and untethered in the body and then taken out and studied with the same method in vitro. Arteries tethered in the body expanded circumferentially more than longitudinally. The tail artery becomes less distensible if untethered in the body and therefore acts more like an aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS)