On constitutive descriptors of the biaxial mechanical behaviour of human abdominal aorta and aneurysms.

The abdominal aorta (AA) in older individuals can develop an aneurysm, which is of increasing concern in our ageing population. The structural integrity of the ageing aortic wall, and hence aneurysm, depends primarily on effective elastin and multiple families of oriented collagen fibres. In this paper, we show that a structurally motivated phenomenological 'four-fibre family' constitutive relation captures the biaxial mechanical behaviour of both the human AA, from ages less than 30 to over 60, and abdominal aortic aneurysms. Moreover, combining the statistical technique known as non-parametric bootstrap with a modal clustering method provides improved confidence intervals for estimated best-fit values of the eight associated constitutive parameters. It is suggested that this constitutive relation captures the well-known loss of structural integrity of elastic fibres owing to ageing and the development of abdominal aneurysms, and that it provides important insight needed to construct growth and remodelling models for aneurysms, which in turn promise to improve our ability to predict disease progression.

3D reconstruction and manufacture of real abdominal aortic aneurysms: from CT scan to silicone model.

Abdominal aortic aneurysm (AAA) can be defined as a permanent and irreversible dilation of the infrarenal aorta. AAAs are often considered to be an aorta with a diameter 1.5 times the normal infrarenal aorta diameter. This paper describes a technique to manufacture realistic silicone AAA models for use with experimental studies. This paper is concerned with the reconstruction and manufacturing process of patient-specific AAAs. 3D reconstruction from computed tomography scan data allows the AAA to be created. Mould sets are then designed for these AAA models utilizing computer aided designcomputer aided manufacture techniques and combined with the injection-moulding method. Silicone rubber forms the basis of the resulting AAA model. Assessment of wall thickness and overall percentage difference from the final silicone model to that of the computer-generated model was performed. In these realistic AAA models, wall thickness was found to vary by an average of 9.21%. The percentage difference in wall thickness recorded can be attributed to the contraction of the casting wax and the expansion of the silicone during model manufacture. This method may be used in conjunction with wall stress studies using the photoelastic method or in fluid dynamic studies using a laser-Doppler anemometry. In conclusion, these patient-specific rubber AAA models can be used in experimental investigations, but should be assessed for wall thickness variability once manufactured.

A model of growth and rupture of abdominal aortic aneurysm.

We present here a coupled mathematical model of growth and failure of the abdominal aortic aneurysm (AAA). The failure portion of the model is based on the constitutive theory of softening hyperelasticity where the classical hyperelastic law is enhanced with a new constant indicating the maximum energy that an infinitesimal material volume can accumulate without failure. The new constant controls material failure and it can be interpreted as the average energy of molecular bonds from the microstructural standpoint. The constitutive model is compared to the data from uniaxial tension tests providing an excellent fit to the experiment. The AAA failure model is coupled with a phenomenological theory of soft tissue growth. The unified theory includes both momentum and mass balance laws coupled with the help of the constitutive equations. The microstructural alterations in the production of elastin and remodeling of collagen are reflected in the changing macroscopic parameters characterizing tissue stiffness, strength and density. The coupled theory is used to simulate growth and rupture of an idealized spherical AAA. The results of the simulation showing possible AAA ruptures in growth are reasonable qualitatively while the quantitative calibration of the model will require further clinical observations and in vitro tests. The presented model is the first where growth and rupture are coupled.

Experimental system for ex vivo measurement of murine aortic stiffness.

While vascular stiffness is universally studied using pulse wave velocity, this method overestimates the stiffness of small calibre blood vessels. We have developed and rigorously validated an ex vivo system for measuring stiffness of the mouse aorta. The system consists of a temperature-controlled tissue bath, a pressurization loop and a helium-neon laser micrometer. We harvested thoracic aortas from 8 (n = 56), 11 (n = 6) and 14 (n = 6) week male C57BL/6J mice, mounted them within a tissue chamber and applied an intraluminal pressure waveform while measuring mid vessel outer diameter. Vessel stiffness (E(p), mmHg) was calculated from the pressure-diameter response. Vessels were then stained for endothelial cells, smooth muscle cells, elastin fibres and collagen. The data indicate highly reproducible stiffness measurements in 8 week mice (E(p) = 602.4 +/- 160.2; p = 0.934), age-related stiffening between 11 and 14 week mice (11 week E(p) = 646.9 +/- 62.4, 14 week E(p) = 795.4 +/- 87.5, p = 0.008), and a morphologically intact vessel wall. These results represent the first ex vivo measurements of murine aortic stiffness and illustrate that our methods are feasible and reliable. Since we demonstrate that the system is sensitive to age-related stiffening and does not damage the vessel, this approach is useful for investigating the pathophysiology of vascular disease from biomechanical and histological perspectives.

Computational modeling of arterial biomechanics: insights into pathogenesis and treatment of vascular disease.

We review how advances in computational techniques are improving our understanding of the biomechanical behavior of the healthy and diseased cardiovascular system. Numerical modeling of biomechanics is being used in a wide variety of ways, including assessment of effects of mural and hemodynamically induced stresses on atherogenesis, development of risk measures for aneurysm rupture, improvement in interpretation of medical images, and quantification of oxygen transport in diseased and healthy arteries. Although not amenable to routine clinical use, numerical modeling of cardiovascular biomechanics is a powerful research tool.

Association of intraluminal thrombus in abdominal aortic aneurysm with local hypoxia and wall weakening.

PURPOSE: Our previous computer models suggested that intraluminal thrombus (ILT) within an abdominal aortic aneurysm (AAA) attenuates oxygen diffusion to the AAA wall, possibly causing localized hypoxia and contributing to wall weakening. The purpose of this work was to investigate this possibility. METHODS: In one arm of this study, patients with AAA were placed in one of two groups: (1) those with an ILT of 4-mm or greater thickness on the anterior surface or (2) those with little (< 4 mm) or no ILT at this site. During surgical resection but before aortic cross-clamping, a needle-type polarographic partial pressure of oxygen (PO2) electrode was inserted into the wall of the exposed AAA, and the PO2 was measured. The probe was advanced, and measurements were made midway through the thrombus and in the lumen. Mural and mid-ILT PO2 measurements were normalized by the intraluminal PO2 measurement to account for patient variability. In the second arm of this study, two AAA wall specimens were obtained from two different sites of the same aneurysm at the time of surgical resection: group I specimens had thick adherent ILT, and group II specimens had thinner or no adherent ILT. Nonaneurysmal tissue was also obtained from the infrarenal aorta of organ donors. Specimens were subjected to histologic, immunohistochemical, and tensile strength analyses to provide data on degree of inflammation (% area inflammatory cells), neovascularization (number of capillaries per high-power field), and tensile strength (peak attainable load). Additional specimens were subjected to Western blotting and immunohistochemistry for qualitative evaluation of expression of the cellular hypoxia marker oxygen-regulated protein. RESULTS: The PO2 measured within the AAA wall in group I (n = 4) and group II (n = 7) patients was 18% +/- 9% luminal value versus 60% +/- 6% (mean +/- SEM; P <.01). The normalized PO2 within the ILT of group I patients was 39% +/- 10% (P =.08 with respect to the group I wall value). Group I tissue specimens showed greater inflammation (P <.05) compared with both group II specimens and nonaneurysmal tissue: 2.9% +/- 0.6% area (n = 7) versus 1.7% +/- 0.3% area (n = 7) versus 0.2% +/- 0.1% area (n = 3), respectively. We found similar differences for neovascularization (number of vessels/high-power field), but only group I versus control was significantly different (P <.05): 16.9 +/- 1.6 (n = 7) vs 13.0 +/- 2.3 (n = 7) vs 8.7 +/- 2.0 (n = 3), respectively. Both Western blotting and immunohistochemistry results suggest that oxygen-regulated protein is more abundantly expressed in group I versus group II specimens. Tensile strength of group I specimens was significantly less (P <.05) than that for group II specimens: 138 +/- 19 N/cm2 (n = 7) versus 216 +/- 34 N/cm2 (n = 7), respectively. CONCLUSION: Our results suggest that localized hypoxia occurs in regions of thicker ILT in AAA. This may lead to increased, localized mural neovascularization and inflammation, as well as regional wall weakening. We conclude that ILT may play an important role in the pathology and natural history of AAA.

The effect of proximal artery flow on the hemodynamics at the distal anastomosis of a vascular bypass graft: computational study.

The formation of distal anastomotic intimal hyperplasia (IH), one common mode of bypass graft failure, has been shown to occur in the areas of disturbed flow particular to this site. The nature of theflow in the segment of artery proximal to the distal anastomosis varies from case to case depending on the clinical situation presented. A partial stenosis of a bypassed arterial segment may allow residual prograde flow through the proximal artery entering the distal anastomosis of the graft. A complete stenosis may allow for zero flow in the proximal artery segment or retrograde flow due to the presence of small collateral vessels upstream. Although a number of investigations on the hemodynamics at the distal anastomosis of an end-to-side bypass graft have been conducted, there has not been a uniform treatment of the proximal artery flow condition. As a result, direct comparison of results from study to study may not be appropriate. The purpose of this work was to perform a three-dimensional computational investigation to study the effect of the proximal artery flow condition (i.e., prograde, zero, and retrograde flow) on the hemodynamics at the distal end-to-side anastomosis. We used the finite volume method to solve the full Navier-Stokes equations for steady flow through an idealized geometry of the distal anastomosis. We calculated the flow field and local wall shear stress (WSS) and WSS gradient (WSSG) everywhere in the domain. We also calculated the severity parameter (SP), a quantification of hemodynamic variation, at the anastomosis. Our model showed a marked difference in both the magnitude and spatial distribution of WSS and WSSG. For example, the maximum WSS magnitude on the floor of the artery proximal to the anastomosis for the prograde and zero flow cases is 1.8 and 3.9 dynes/cm2, respectively, while it is increased to 10.3 dynes/cm2 in the retrograde flow case. Similarly, the maximum value of WSSG magnitude on thefloor of the artery proximal to the anastomosis for the prograde flow case is 4.9 dynes/cm3, while it is increased to 13.6 and 24.2 dynes/cm3, respectively, in the zero and retrograde flow cases. The value of SP is highest for the retrograde flow case (13.7 dynes/cm3) and 8.1 and 12.1 percent lower than this for the prograde (12.6 dynes/cm3) and zero (12.0 dynes/cm3) flow cases, respectively. Our model results suggest that the flow condition in the proximal artery is an important determinant of the hemodynamics at the distal anastomosis of end-to-side vascular bypass grafts. Because hemodynamic forces affect the response of vascular endothelial cells, the flow situation in the proximal artery may affect IH formation and, therefore, long-term graft patency. Since surgeons have some control over the flow condition in the proximal artery, results from this study could help determine which flow condition is clinically optimal.

Mechanical properties and microstructure of intraluminal thrombus from abdominal aortic aneurysm.

Accurate estimation of the wall stress distribution in an abdominal aortic aneurysm (AAA) may prove clinically useful by predicting when a particular aneurysm will rupture. Appropriate constitutive models for both the wall and the intraluminal thrombus (ILT) found in most AAA are necessary for this task. The purpose of this work was to determine the mechanical properties of ILT within AAA and to derive a more suitable constitutive model for this material. Uniaxial tensile testing was carried out on 50 specimens, including 14 longitudinally oriented and 14 circumferentially oriented specimens from the luminal region of the ILT, and 11 longitudinally oriented and 11 circumferentially oriented specimens from the medial region. A two-parameter, large-strain, hyperelastic constitutive model was developed and used to fit the uniaxial tensile testing data for determination of the material parameters. Maximum stiffness and strength were also determined from the data for each specimen. Scanning electron microscopy (SEM) was conducted to study the regional microstructural difference. Our results indicate that the microstructure of ILT differs between the luminal, medial, and abluminal regions, with the luminal region stronger and stiffer than the medial region. In all cases, the constitutive model fit the experimental data very well (R2>0.98). No significant difference was found for either of the two material parameters between longitudinal and circumferential directions, but a significant difference in material parameters, stiffness, and strength between the laminal and medial regions was determined (p<0.01). Therefore, our results suggest that ILT is an inhomogeneous and possibly isotropic material. The two-parameter, hyperelastic, isotropic, incompressible material model derived here for ILT can be easily incorporated into finite element models for simulation of wall stress distribution in AAA.

Surface geometric analysis of anatomic structures using biquintic finite element interpolation.

The surface geometry of anatomic structures can have a direct impact upon their mechanical behavior in health and disease. Thus, mechanical analysis requires the accurate quantification of three-dimensional in vivo surface geometry. We present a fully generalized surface fitting method for surface geometric analysis that uses finite element based hermite biquintic polynomial interpolation functions. The method generates a contiguous surface of C2 continuity, allowing computation of the finite strain and curvature tensors over the entire surface with respect to a single in-surface coordinate system. The Sobolev norm, which restricts element length and curvature, was utilized to stabilize the interpolating polynomial at boundaries and in regions of sparse data. A major advantage of the current method is its ability to fully quantify surface deformation from an unstructured grid of data points using a single interpolation scheme. The method was validated by computing both the principal curvature distributions for phantoms of known curvatures and the principal stretch and principal change of curvature distributions for a synthetic spherical patch warping into an ellipsoidal shape. To demonstrate the applicability to biomedical problems, the method was applied to quantify surface curvatures of an abdominal aortic aneurysm and the principal strains and change of curvatures of a deforming bioprosthetic heart valve leaflet. The method proved accurate for the computation of surface curvatures, as well as for strains and curvature change for a surface undergoing large deformations.

Toward a biomechanical tool to evaluate rupture potential of abdominal aortic aneurysm: identification of a finite strain constitutive model and evaluation of its applicability.

Knowledge of the wall stresses in an abdominal aortic aneurysm (AAA) may be helpful in evaluating the need for surgical intervention to avoid rupture. This must be preceded by the development of a more suitable finite strain constitutive model for AAA, as none currently exists. Additionally, reliable stress analysis of in vivo AAA for the purposes of clinical diagnostics requires patient-specific values of the material parameters, which are difficult to determine noninvasively. The purpose of this work, therefore, was three-fold: (1) to develop a finite strain constitutive model for AAA; (2) to estimate the variation of model parameters within a sample population; and (3) to evaluate the sensitivity of computed stress distribution in AAA due to this biologic variation. We propose here a two parameter, hyperelastic, isotropic, incompressible material model and utilize experimental data from 69 freshly excised AAA specimens to both develop the functional form of the model and estimate its material parameters. Parametric analyses were performed via repeated finite element computations to determine the effect of varying each of the two model parameters on the stress distribution in a three-dimensional AAA model. The agreement between experimental data and the proposed functional form of the constitutive law was very good (R2 > 0.9). Our finite element simulations showed that the computed AAA wall stresses changed by only 4% or less when both the parameters were varied within the 95% confidence intervals for the patient population studied. This observation indicates that in lieu of the patient-specific material parameters, which are difficult to determine the use of population mean values is sufficiently accurate for the model to be reasonably employed in a clinical setting. We believe that this is an important advancement toward the development of a computational tool for the estimation of rupture potential for individual AAA, for which there is great clinical need.

Wall stress distribution on three-dimensionally reconstructed models of human abdominal aortic aneurysm.

PURPOSE: Abdominal aortic aneurysm (AAA) rupture is believed to occur when the mechanical stress acting on the wall exceeds the strength of the wall tissue. Therefore, knowledge of the stress distribution in an intact AAA wall could be useful in assessing its risk of rupture. We developed a methodology to noninvasively estimate the in vivo wall stress distribution for actual AAAs on a patient-to-patient basis. METHODS: Six patients with AAAs and one control patient with a nonaneurysmal aorta were the study subjects. Data from spiral computed tomography scans were used as a means of three-dimensionally reconstructing the in situ geometry of the intact AAAs and the control aorta. We used a nonlinear biomechanical model developed specifically for AAA wall tissue. By means of the finite element method, the stress distribution on the aortic wall of all subjects under systolic blood pressure was determined and studied. RESULTS: In all the AAA cases, the wall stress was complexly distributed, with distinct regions of high and low stress. Peak wall stress among AAA patients varied from 29 N/cm(2) to 45 N/cm(2) and was found on the posterior surface in all cases studied. The wall stress on the nonaneurysmal aorta in the control subject was relatively low and uniformly distributed, with a peak wall stress of 12 N/cm(2). AAA volume, rather than AAA diameter, was shown by means of statistical analysis to be a better indicator of high wall stresses and possibly rupture. CONCLUSION: The approach taken to estimate AAA wall stress distribution is completely noninvasive and does not require any additional involvement or expense by the AAA patient. We believe that this methodology may allow for the evaluation of an individual AAA's rupture risk on a more biophysically sound basis than the widely used 5-cm AAA diameter criterion.

In vivo three-dimensional surface geometry of abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) is a local, progressive dilation of the distal aorta that risks rupture until treated. Using the law of Laplace, in vivo assessment of AAA surface geometry could identify regions of high wall tensions as well as provide critical dimensional and shape data for customized endoluminal stent grafts. In this study, six patients with AAA underwent spiral computed tomography imaging and the inner wall of each AAA was identified, digitized, and reconstructed. A biquadric surface patch technique was used to compute the local principal curvatures, which required no assumptions regarding axisymmetry or other shape characteristics of the AAA surface. The spatial distribution of AAA principal curvatures demonstrated substantial axial asymmetry, and included adjacent elliptical and hyperbolic regions. To determine how much the curvature spatial distributions were dependent on tortuosity versus bulging, the effects of AAA tortuosity were removed from the three-dimensional (3D) reconstructions by aligning the centroids of each digitized contour to the z axis. The spatial distribution of principal curvatures of the modified 3D reconstructions were found to be largely axisymmetric, suggesting that much of the surface geometric asymmetry is due to AAA bending. On average, AAA surface area increased by 56% and abdominal aortic length increased by 27% over those for the normal aorta. Our results indicate that AAA surface geometry is highly complex and cannot be simulated by simple axisymmetric models, and suggests an equally complex wall stress distribution.

Gene expression is altered in perfused arterial segments exposed to cyclic flexure ex vivo.

Certain regions of coronary and other arteries undergo cyclic flexure due to attachment to the heart or crossing of joints. Such motion gives rise to fluctuations in transmural stress and luminal shear stress. It is well known that cyclic variation of these biomechanical forces influences many aspects of vascular cell biology including gene expression. The purpose of this work was to investigate the hypothesis that cyclic flexure of arterial segments influences their gene expression. Bilateral porcine femoral arteries were obtained fresh from the abattoir. One vessel was mounted in an ex vivo perfusion system and subjected to an intraluminal pressure of 60 mmHg and flow of 50 ml/min to serve as a control. The other vessel was mounted in a second perfusion system with similar hemodynamic conditions, but also subjected to controlled cyclic bending consistent with that found in coronary arteries in vivo. Reverse transcriptase-polymerase chain reaction analysis demonstrated that E-selectin and matrix metalloproteinase-1 (MMP-1) were consistently and significantly downregulated in the specimens subjected to 4 h of cyclic bending as compared to the control (n = 8, p < 0.05). Our results show that cyclic flexure of arterial segments in vitro may influence their gene expression. Further investigation should follow this novel observation and focus on other known mediators to more carefully elucidate the consequence of cyclic flexure on arterial pathobiology.

Micromechanical devices for intravascular drug delivery.

Microfabrication technology, more commonly applied to the manufacture of integrated circuits, can be used to build devices useful for mechanical delivery of drugs and genes. Microprobes fabricated using silicon micromachining have been used to deliver DNA into cells as an alternative to bombardment and microinjection. This idea can be extended to intravascular stents with integrated microprobes capable of piercing compressed plaque and delivering anti-restenosis therapies into coronary arteries. Preliminary experiments using filleted rabbit arteries have demonstrated transection of the internal elastic lamina. New nonplanar microfabrication technologies are necessary for creating practical devices with cylindrical symmetry; a promising possibility is to use microfabricated structures of anodic metal oxides.

Arterial hemodynamics and wall mechanics.

Arterial hemodynamics and wall mechanics are important considerations for the vascular clinician for a number of reasons. Hemodynamics and wall mechanics both have been shown to be affecters of disease formation. It is important for the practicing vascular surgeon to know how disease affects both blood flow and wall mechanics and to understand the consequence of hemodynamics on arterial reconstructions. In this article, we summarize the basic concepts of arterial hemodynamics and wall mechanics as they relate to the development of arterial pathology. A few practical mathematical relationships and examples are provided for both illustration and utilization. We also discuss the use of computer models for the estimation of wall stresses in individual abdominal aortic aneurysms.

Mechanical wall stress in abdominal aortic aneurysm: influence of diameter and asymmetry.

PURPOSE: Risk for rupture of an abdominal aortic aneurysm is widely believed to be related to its maximum diameter. From a biomechanical standpoint, however, risk is probably more precisely related to mechanical wall stress. Many abdominal aortic aneurysms are asymmetric (for example because of anterior bulging with posterior expansion limited by the vertebral column). The purpose of this work was to investigate the effect of maximum diameter and asymmetric bulge on wall stress. METHODS: Three-dimensional computer models of abdominal aortic aneurysms were generated. In one protocol, maximum diameter was held constant while bulge shape factor was varied. The shape factor took into account the asymmetric shape of the bulge. In a second protocol, the shape of the aneurysmal wall was held constant while maximum diameter was varied. Wall stress was computed in each instance with a commercial software package and assumption of physiologic intraluminal pressure. RESULTS: Both maximum diameter and the shape factor were found to have substantial influence on the distribution of wall stress within the aneurysm. In some instances the maximum stress occurred at the midsection, and in others it occurred elsewhere. The magnitude of peak stress acting on the aneurysm increased nonlinearly with increasing maximum diameter or increasing asymmetry. CONCLUSIONS: Our computer models showed that the stress within the wall of an abdominal aortic aneurysm and possibly the potential for rupture are as dependent on aneurysm shape as they are on maximum diameter. This information may be important in determining severity of individual abdominal aortic aneurysms and in improving understanding of the natural history of the disease.

Enhancement of tissue factor expression by vein segments exposed to coronary arterial hemodynamics.

PURPOSE: Although saphenous vein is the most reliable conduit for arterial interposition procedures in the coronary circulation, graft thrombosis remains a clinical problem. We hypothesized that an important factor in early graft thrombosis is sudden change in the hemodynamic environment of the vein as it is placed in the coronary circulation. METHODS: We used an ex vivo perfusion system to study freshly excised segments of human saphenous vein (HSV) and pig internal jugular vein. For coronary graft (CAVG) simulation, sections of HSV were subjected to arterial pulsatile pressure and flow and twisting and stretching to mimic deformations caused by the beating heart. Using functional and immunohistochemical assays, we investigated the effect of these conditions on expression of tissue factor (TF), an important prothrombotic surface molecule. RESULTS: In each of 11 experiments (6 human, 5 porcine), vein segments from a single donor were subjected to venous conditions (VEN), CAVG perfusion, or no perfusion. Expression of TF was measured as the amount of factor Xa generated per unit area of luminal vein surface. VEN perfusion did not cause a significant change in mean TF expression over nonperfused control values (human: 14.3 +/- 1.5 versus 11.4 +/- 2.3 U/cm2, p = 0.31; pig: 11.6 +/- 1.5 versus 12.5 +/- 1.4 U/cm2, p = 0.70). CAVG perfusion led to significant enhancement of TF expression over VEN perfusion (human: 36.8 +/- 6.2 versus 14.3 +/- 1.5 U/cm2, p < 0.05; pig: 40.0 +/- 9.9 versus 11.6 +/- 1.5 U/cm2, p < 0.05). Immunohistochemical analysis showed positive TF staining on the luminal side of a CAVG-stimulated HSV segment, but not on a VEN-stimulated segment. In four additional studies, HSV segments were subjected to arterial perfusion without twist and stretch to mimic lower extremity arterial interposition grafts. TF expression for lower extremity venous graft perfusion was significantly higher than for VEN perfusion (25.3 +/- 2.5 versus 14.3 +/- 1.5, p < 0.01) but not significantly different from CAVG perfusion. CONCLUSIONS: Our studies in a unique perfusion system suggest that exposure of vein to coronary arterial hemodynamic conditions results in elevated expression of the important prothrombotic molecule TF. This phenomenon may contribute to early graft thrombosis.

Effect of intraluminal thrombus thickness and bulge diameter on the oxygen diffusion in abdominal aortic aneurysm.

The intraluminal thrombus (ILT) commonly found within abdominal aortic aneurysm (AAA) may serve as a barrier to oxygen diffusion from the lumen to the inner layers of the aortic wall. The purpose of this work was to address this hypothesis and to assess the effects of AAA bulge diameter (dAAA) and ILT thickness (delta) on the oxygen flow. A hypothetical, three-dimensional, axisymmetric model of AAA containing ILT was created for computational analysis. Commercial software was utilized to estimate the volume flow of O2 per cell, which resulted in zero oxygen tension at the AAA wall. Solutions were generated by holding one of the two parameters fixed while varying the other. The supply of O2 to the AAA wall increases slightly and linearly with dAAA for a fixed delta. This slight increase is due to the enlarged area through which diffusion of O2 may take place. The supply of O2 was found to decrease quickly with increasing delta for a fixed dAAA due to the increased resistance to O2 transport by the ILT layer. The presence of even a thin, 3 mm ILT layer causes a diminished O2 supply (less than 4 x 10(-10) mumol/min/cell). Normally functioning smooth muscle cells require a supply of 21 x 10(-10) mumol/min/cell. Thus, our analysis serves to support our hypothesis that the presence of ILT alters the normal pattern of O2 supply to the AAA wall. This may lead to hypoxic cell dysfunction in the AAA wall, which may further lead to wall weakening and increased potential for rupture.

Effect of retroviral transduction on human endothelial cell phenotype and adhesion to Dacron vascular grafts.

PURPOSE: Retroviral transduction for genetic enhancement of endothelial cell (EC) anti-thrombotic phenotype offers potential for improving the clinical success of vascular graft seeding; however, application of this technique may bring concomitant alteration in cell functionality. METHODS: Human microvascular ECs were transduced with a retroviral vector encoding for the marker gene beta-galactosidase. Transduced endothelial cells (rtECs) and nontransduced endothelial cells (ntECs) were evaluated by flow cytometry for expression of intercellular adhesion molecule (ICAM)-1 and tissue factor (TF) on both smooth (coverslips) and graft (Dacron, 6 mm inside diameter) surfaces under static and shear exposed conditions. Graft EC retention was measured after 6-hour pulsatile perfusions. Platelet and neutrophil adherence was measured on perfused coverslips. RESULTS: Lower levels of ICAM-1 were expressed by rtECs on coverslips under both static (p < 0.01 vs static ntECs) and shear exposed conditions (p < 0.01 vs static and shear ntECs). Accordingly, fewer polymorphonuclear leukocytes adhered to rtEC monolayers (p < 0.01 vs ntECs). No difference in ICAM-1 and TF expression by static graft seeded rtECs and ntECs was observed. However, graft-seeded rtECs that were exposed to wall shear stress displayed less TF than sheared ntECs (p < 0.05). Transduction did not affect EC retention to the sheared graft surface. CONCLUSIONS: These data suggest that retroviral transduction does not elicit a prothrombotic/proinflammatory phenotype, rather indices of these states appear in some conditions to be reduced. Further, transduction does not adversely affect EC adherence to Dacron graft surfaces under arterial hemodynamics.

Cellular content and permeability of intraluminal thrombus in abdominal aortic aneurysm.

PURPOSE: A pathologic feature commonly associated with abdominal aortic aneurysms is the presence of variably sized and shaped intraluminal thrombus, which may be fundamental to the disease process. However, the precise role of the intraluminal thrombus in the formation, enlargement, and rupture of abdominal aortic aneurysms is unknown. The hypothesis tested in this study was whether there were structural features of aortic thrombi to suggest that it may be involved in the pathogenesis of abdominal aortic aneurysms. We have investigated this hypothesis using a variety of structural and biochemical techniques. METHODS: Tests performed were light, transmission, and scanning electron microscopy; fluid permeability measurements; and Western blots. RESULTS: Intraluminal thrombus found in abdominal aortic aneurysms is structurally complex and is traversed from the luminal to abluminal surface by a continuous network of interconnected canaliculi. Quantitative microscopic analysis of the thrombus shows cellular penetration for at least 1 cm from the luminal surface of the thrombus. Macro-molecular penetration may be unrestricted throughout the entire thickness of the thrombus. Fibrin deposition occurred throughout the thrombus, whereas fibrin degradation occurred principally at the abluminal surface. CONCLUSIONS: These principally structural studies support the hypothesis that the thrombus is a self-sustaining entity that may have significance in the pathophysiologic mechanism of abdominal aortic aneurysms.