Richard L. Leask

Local mechanical and structural properties of healthy and diseased human ascending aorta tissue

OBJECTIVE This study investigates the mechanics and histology of healthy and dilated human ascending aortas (AA). The regional variation in mechanical response and tissue structure were compared. METHODS Rings of human AA from healthy (n=5), dilated tricuspid aortic valve (TAV, n=5), and dilated bicuspid aortic valve (BAV, n=6) patients were mechanically tested. Each aortic ring was sectioned into quadrants-anterior, posterior, medial (inner curvature) and lateral (outer curvature). Low- and high-stress elastic moduli were calculated from the equibiaxial stress strain curve to determine the local mechanical properties. Histological analysis was used to quantify the percent composition of elastin, collagen, and smooth muscle cells. RESULTS BAV tissue was thinnest and contained the largest percent composition of collagen. Both TAV and BAV tissue had significantly less elastin than healthy tissue. At low strain in the circumferential direction, TAV tissue was on average the least stiff. The elastic modulus was dependent on quadrant and tissue type but not direction (isotropic). Generally, the lateral quadrant tissue was the stiffest and the medial quadrant the least stiff. There were no apparent local variations in the tissue histology. CONCLUSIONS Local variations in tissue thickness and mechanical properties were evident in all samples analyzed and may be linked to the type of aortic valve present.

Cell treatment and surface functionalization using a miniature atmospheric pressure glow discharge plasma torch

A miniature atmospheric pressure glow discharge plasma torch was used to detach cells from a polystyrene Petri dish. The detached cells were successfully transplanted to a second dish and a proliferation assay showed the transplanted cells continued to grow. Propidium iodide diffused into the cells, suggesting that the cell membrane had been permeabilized, yet the cells remained viable 24 h after treatment. In separate experiments, hydrophobic, bacteriological grade polystyrene Petri dishes were functionalized. The plasma treatment reduced the contact angle from 93° to 35°, and promoted cell adhesion. Two different torch nozzles, 500 µm and 150 µm in internal diameter, were used in the surface functionalization experiments. The width of the tracks functionalized by the torch, as visualized by cell adhesion, was approximately twice the inside diameter of the nozzle. These results indicate that the miniature plasma torch could be used in biological micropatterning, as it does not use chemicals like the present photolithographic techniques. Due to its small size and manouvrability, the torch also has the ability to pattern complex 3D surfaces.

Intimal Thickness Is not Associated With Wall Shear Stress Patterns in the Human Right Coronary Artery

Objective—Low wall shear stress has been implicated in atherogenesis throughout the arterial tree, including the right coronary artery (RCA). The objective of this study was to determine the level of covariation of intimal thickness and wall shear stress in the human RCA. Methods and Results—Postmortem histological measurements of intimal thickness were compared with wall shear stresses calculated from computational flow modeling in 4 human right coronary arteries. A statistically significant correlation between intimal thickness and wall shear stress was found in only 1 of the 4 arteries studied. Conclusion—Wall shear stress does not appear to be related to intimal thickness in the 4 RCAs studied.

A Comparison of Mechanical Properties of Materials Used in Aortic Arch Reconstruction

BACKGROUND Differences in the mechanical properties of aortic tissues and replacement materials can have unwanted hemodynamic effects leading to graft failure. The aim of this experimental study was to compare the mechanical properties of different graft-patch materials used in aortic arch reconstruction with those of healthy and dilated human ascending aortas (AAs). METHODS Four square samples were taken from 30 healthy (n = 120) and 14 dilated (n = 56) AA rings and from 34 human pericardial sections (fresh [n = 68] and Carpentiers solution fixed [n = 68]). In addition, square samples from commercial bovine pericardium (n = 14) were also compared with woven Dacron grafts (n = 24) and tested biaxially. Stress-strain curves (0% to 30%) were generated using a biaxial tensile tester to quantify the anisotropic properties and stiffness of the materials at 37 degrees C. RESULTS We found significant differences in stiffness and anisotropy among all material types. Fresh and fixed human pericardia, bovine pericardium, and Dacron were 9.5, 7.1, 16.4, and 18.4 times stiffer than dilated AAs, which was 1.3 times stiffer than healthy AAs under physiologic stretch. Only dilated and healthy AAs showed an increase in anisotropic properties with increasing strain. CONCLUSIONS The significant differences in the mechanical properties among all materials we found are intended to increase the awareness of these differences in materials used in aortic reconstruction surgery. This finding suggests that improvements are needed in prosthetic material design to better mimic native tissue.

Leaching of the plasticizer di(2-ethylhexyl)phthalate (DEHP) from plastic containers and the question of human exposure

Di(2-ethylhexyl)phthalate (DEHP) is a widely used plasticizer to render poly(vinyl chloride) (PVC) soft and malleable. Plasticized PVC is used in hospital equipment, food wrapping, and numerous other commercial and industrial products. Unfortunately, plasticizers can migrate within the material and leach out of it over time, ending up in the environment and, frequently, the human body. DEHP has come under increased scrutiny as its breakdown products are believed to be endocrine disruptors and more toxic than DEHP itself. DEHP and its breakdown products have been identified as ubiquitous environmental contaminants, and daily human exposure is estimated to be in the microgram per kilogram level. The objective of this review is to summarize and comment on published sources of DEHP exposure and to give an overview of its environmental fate. Exposure through bottled water was examined specifically, as this concern is raised frequently, yet only little exposure to DEHP occurs through bottled water, and DEHP exposure is unlikely to stem from the packaging material itself. Packaged food was also examined and showed higher levels of DEHP contamination compared to bottled water. Exposure to DEHP also occurs in hospital environments, where DEHP leaches directly into liquids that passed through PVC/DEHP tubing and equipment. The latter exposure is at considerably higher levels compared to food and bottled water, specifically putting patients with chronic illnesses at risk. Overall, levels of DEHP in food and bottled water were below current tolerable daily intake (TDI) values. However, our understanding of the risks of DEHP exposure is still evolving. Given the prevalence of DEHP in our atmosphere and environment, and the uncertainty revolving around it, the precautionary principle would suggest its phaseout and replacement. Increased efforts to develop viable replacement compounds, which necessarily includes rigorous leaching, toxicity, and impact assessment studies, are needed before alternative plasticizers can be adopted as viable replacements.

Miniature atmospheric pressure glow discharge torch (APGD- t ) for local biomedical applications

The operating parameters of a miniature atmospheric pressure glow discharge torch (APGD-t) are optimized for the production of excited atomic oxygen, and the effect of the plasma jet on endothelial cells grown in Petri dishes is studied. We first demonstrate the importance of accounting for the effect of the voltage probe used to measure the electrical parameters of the torch on its ignition and operation characteristics. When operated with a main plasma gas flow rate of 1 SLM He and a power level of ~1 W, the torch shows an optimum in the production of excited atomic oxygen for a O2 flow of ~3.5 SCCM injected downstream from the plasma-forming region through a capillary electrode (i.e., 0.35 v/v % O2/He). It is shown that endothelial cells are detached from the Petri dishes surface under the action of the optimized plasma jet and that this effect does not originate from heating and fluid shearing effects. It is postulated that the cell detachment is caused solely by plasma-induced biochemical processes taking place at the cell-substrate interface.

Effects of diffusion coefficients and struts apposition using numerical simulations for drug eluting coronary stents.

In the context of drug eluting stent, we present two-dimensional numerical models of mass transport of the drug in the wall and in the lumen to study the effect of the drug diffusion coefficients in the three principal media (blood, vascular wall, and polymer coating treated as a three-compartment problem) and the impact of different strut apposition configurations (fully embedded, half embedded, and not embedded). The different conditions were analyzed in terms of their consequence on the drug concentration distribution in the arterial wall. We apply the concept of the therapeutic window to the targeted vascular wall region and derive simple metrics to assess the efficiency of the various stent configurations. Although most of the drug is dispersed in the lumen, variations in the blood flow rate within the physiological range of coronary blood flow and the diffusivity of the drug molecule in the blood were shown to have a negligible effect on the amount of drug in the wall. Our results reveal that the amount of drug cumulated in the wall depends essentially on the relative values of the diffusion coefficients in the polymer coating and in the wall. Concerning the strut apposition, it is shown that the fully embedded strut configuration would provide a better concentration distribution.

Hemodynamic Effects of Clot Entrapment in the TrapEase Inferior Vena Cava Filter

PURPOSE The TrapEase vena cava filter has a symmetric design. Emboli can be trapped in the outlet conical section (superior cone) or between the filter and vessel wall at the inlet end (inferior cone). The purpose of this in vitro study is to investigate the hemodynamic effects of clot entrapment by the TrapEase filter and to examine the possibility of flow-induced filter thrombosis. MATERIALS AND METHODS Velocity and wall shear stress maps were determined for steady flow with use of the photochromic flow visualization technique. Experiments were done for a filter without clot and for three other cases: an asymmetric clot in the inferior zone, a symmetric clot in the superior zone, and a filter with both zones partially occluded. Each simulated clot was 1500 mm(3) and the vessel diameter was 2 cm. RESULTS The unoccluded filter did not significantly affect the flow field. However, for a partially occluded filter, flow stagnation/recirculation and turbulence developed downstream from the clot. The greatest effect was noted when the clot was against the vessel wall in the inferior trapping region. CONCLUSIONS The tendency for clots to be trapped between the filter and the vessel wall in the inferior (inlet) region may play an important role in the performance of the TrapEase filter. A clot in this configuration will generate a large region of flow stagnation/recirculation that is considered to be prothrombotic. In addition, a significant amount of the filter wire will be embedded in this region, which may also promote thrombosis.

The relationship between wall shear stress distributions and intimal thickening in the human abdominal aorta

PurposeThe goal of this work was to determine wall shear stress (WSS) patterns in the human abdominal aorta and to compare these patterns to measurements of intimal thickness (IT) from autopsy samples.MethodsThe WSS was experimentally measured using the laser photochromic dye tracer technique in an anatomically faithful in vitro model based on CT scans of the abdominal aorta in a healthy 35-year-old subject. IT was quantified as a function of circumferential and axial position using light microscopy in ten human autopsy specimens.ResultsThe histomorphometric analysis suggests that IT increases with age and that the distribution of intimal thickening changes with age. The lowest WSS in the flow model was found on the posterior wall inferior to the inferior mesenteric artery, and coincided with the region of most prominent IT in the autopsy samples. Local geometrical features in the flow model, such as the expansion at the inferior mesenteric artery (common in younger individuals), strongly influenced WSS patterns. The WSS was found to correlate negatively with IT (r2 = 0.3099; P = 0.0047).ConclusionLow WSS in the abdominal aorta is co-localized with IT and may be related to atherogenesis. Also, rates of IT in the abdominal aorta are possibly influenced by age-related geometrical changes.

The development of 3-D, in vitro, endothelial culture models for the study of coronary artery disease

The response of the vascular endothelium to wall shear stress plays a central role in the development and progression of atherosclerosis. Current studies have investigated endothelial response using idealized in vitro flow chambers. Such cell culture models are unable to accurately replicate the complex in vivo wall shear stress patterns arising from anatomical geometries. To better understand this implication, we have created both simplified/tubular and anatomically realistic in vitro endothelial flow models of the human right coronary artery. A post-mortem vascular cast of the human left ventricular outflow tract was used to create geometrically accurate silicone elastomer models. Straight, tubular models were created using a custom made mold. Following the culture of human abdominal aortic endothelial cells within the inner lumen, cells were exposed to steady flow (Re = 233) for varying time periods. The resulting cell morphology was analyzed in terms of shape index and angle of orientation relative to the flow direction. In both models a progressive elongation and alignment of the endothelium in the flow direction was observed following 8, 12, and 24 hours. This change, however, was significantly less pronounced in the anatomical model (as observed from morphological variations indicative of localized flow features). Differences were also observed between the inner and outer walls at the disease-prone proximal region. Since morphological adaptation is a visual indication of endothelial shear stress activation, the use of anatomical models in endothelial genetic and biochemical studies may offer better insight into the disease process.