Regional distribution of layer-specific circumferential residual deformations and opening angles in the porcine aorta

Information on the layer-specific residual deformations of aortic tissue and how these vary throughout the vessel is important for understanding the regionally-varying aortic functions and pathophysiology, but not so much can be found in the literature. Toward this end, porcine aortas were sectioned into eighteen rings, with one ring from each anatomical position radially cut to obtain the zero-stress state for the intact wall and the other ring dissected into intimal-medial and adventitial layers; these rings were then radially cut to reach the zero-stress state for the intima-media and adventitia. Peripheral variations in internal/external circumferences, thickness, and opening angle of the intact wall and its layers were measured through image analysis at the no-load and zero-stress states. Intact wall and layer circumferences at both states significantly declined along the aorta, as did intact wall and intimal-medial but not adventitial thickness. Adventitia exhibited the greatest opening angles, approaching 180 deg all over the aorta. The opening angles of the intima-media and intact wall were quite similar, with the highest values in the ascending aorta, the lowest at the diaphragm, and increasing subsequently. Bending-related residual stretches were released by radial cutting that were compressive internally and tensile externally, displaying distinct axial variation for the intima-media and intact wall, and non-significant variation for the adventitia. Evidence is provided for the release upon layer separation of compressive stretches in the intima-media and of tensile stretches in the adventitia, whose values were smallest in the descending thoracic aorta and highest near the iliac artery bifurcation.     

Opening angle and residual strain in a three-layered model of pig oesophagus

Studies of various biological tissues have shown that residual strains are important for tissue function. Since a force balance exists in whole wall thickness specimens cut radially, it is evident that layer separation is an important procedure in the understanding of the meaning of residual stresses and strains. The present study investigated the zero-stress state and residual strain distribution in a three-layer model of the pig oesophagus. The middle part of the oesophagus was obtained from six slaughterhouse pigs. Four 3-mm-wide rings were serially cut from each oesophagus. Two of them were used for separating the wall into mucosa-submucosa, inner and outer muscle layers. The remaining two rings were kept as intact rings. The inner and outer circumferences and wall thickness of different layers in intact and separated rings were measured from the digital images in the no-load state and zero-stress state. The opening angle was measured and the residual strain at the inner and outer surface of different layers and the intact wall were computed. Compared with intact sectors (62.8+/-9.8 degrees ), the opening angles were smaller in the inner muscle sectors (37.2+/-11.4 degrees , P<0.01), whereas the opening angles of mucosa-submucosa (63.9+/-6.8 degrees ) and outer muscle sectors (63.9+/-6.8 degrees ) did not differ (P>0.1). Referenced to the zero-stress state of the intact sectors, the inner and outer residual strains of the intact rings was -0.128+/-0.043 and outer residual strain was 0.308+/-0.032. Referenced to the "true" zero-stress state of separated three-layered sectors, the inner residual strain of intact rings were -0.223+/-0.021 (P<0.01) and 0.071+/-0.022 (P<0.01). Referenced to the "true" zero-stress state, the residual strain distribution of different layers in intact rings was shown that the inner surface residual strain was negative at mucosa-submucosa and inner muscle layers and was positive at outer muscle layer, whereas the outer surface residual strain was negative at the mucosa-submucosa layer and positive at the inner and outer muscle layers. For the separated different layered rings, the inner residual strain was negative and outer residual strain was positive; however, the absolute values did not differ (P>0.1). In conclusion, it is possible to microsurgically separate the oesophagus into three layers, i.e., mucosa-submucosa, inner muscle and outer muscle layers, the residual strain differ between the layers, and the residual strain distribution was more uniform after the layers were separated.     

3D computational parametric analysis of eccentric atheroma plaque: influence of axial and circumferential residual stresses

Plaque rupture plays a role in the majority of acute coronary syndromes. Rupture has usually been associated with stress concentrations, which are mainly affected by the plaque geometry and the tissue properties. The aim of this study is to evaluate the influence of morphology on the risk of plaque rupture, including the main geometrical factors, and to assess the role of circumferential and axial residual stresses by means of a parametric 3D finite element model. For this purpose, a 3D parametric finite element model of the coronary artery with eccentric atheroma plaque was developed. Healthy (adventitia and media in areas without atheroma plaque) and diseased (fibrotic and lipidic) tissues were considered in the model. The geometrical parameters used to define and design the idealized coronary plaque anatomy were the lipid core length, the stenosis ratio, the fibrous cap thickness, and the lipid core ratio. Finally, residual stresses in longitudinal and circumferential directions were incorporated into the model to analyse the influence of the important mechanical factors in the vulnerability of the plaque. Viewing the results, we conclude that residual stresses should be considered in the modelling of this kind of problems since they cause a significant alteration of the vulnerable plaque region limits. The obtained results show that the fibrous cap thickness and the lipid core length, in combination with the lipid core width, appear to be the key morphological parameters that play a determinant role in the maximal principal stress (MPS). However, the stenosis ratio is found to not play a significant role in vulnerability related to the MPS. Plaque rupture should therefore be observed as a consequence, not only of the cap thickness, but as a combination of the stenosis ratio, the fibrous cap thickness and the lipid core dimensions.     

Regional distribution of catecholamines in nucleus accumbens of the rabbit

Abstract: The nucleus accumbens is an important telencephalic region, which is the target limbic and mesolimbic pathways. Because of an ongoing physiological study of the effects of dopamine, we wanted to determine regional differences of dopamine and norepinephrine concentrations in the nucleus. As determined by radioenzymatic assays, dopamine levels were not significantly different in the anterior-posterior dimension, averaging approximately 187 ng dopamine/mg protein. Substantial amounts of norepinephrine were found throughout the nucleus, but the levels were significantly higher in the caudal portions of the nucleus, being approximately 4.5 times higher than in the anterior portions.     

Regional distribution of choline acetyltransferase and acetylcholinesterase in rabbit brain

Regional distribution of choline acetyltransferase (CAT) and acetylcholinesterase (AChE) in seventeen regions of the rabbit CNS has been determined by means of the cation exchange radiometric method. A significant correlation has been found between the activities of AChE and CAT which allows computation of their potencies. A comparison between activities of the cholinergic enzymes in the human and rabbit brain has been discussed.     

Regional distribution of glutathione-related antioxidant defences in the normal rabbit aorta

In 6 normal rabbits, the aortic arch, the descending thoracic and the abdominal aorta were tested for non proteic thiol compounds, selenium-dependent and selenium-independent glutatione peroxidase, glutatione reductase, glutatione transferase and thiobarbituric acid reactive substances. The aortic arch showed the greatest content of non proteic thiol compounds and thiobarbituric acid reactive substances, associated to the highest activities of glutathione-related enzymes. However, not significant differences were detectable between aortic arch and descending thoracic aorta, except for the glutathione transferase activity (0.395 +/- 0.031 vs 0.330 +/- 0.053 U/mg protein, p less than 0.05). Furthermore, both aortic arch and descending thoracic aorta showed significantly higher values of non proteic thiol compounds (46.05 +/- 10.15% and 33 +/- 13.5%, p less than 0.05), selenium-dependent glutathione peroxidase activity (70.35 +/- 26% and 54.3 +/- 9.5%, p less than 0.05), glutathione reductase activity (25.4 +/- 7% and 18.4 +/- 4.5%, p less than 0.05) and thiobarbituric acid reactive substances (65.8 +/- 18% and 47.2 +/- 17%, p less than 0.05) with respect to the abdominal aorta. The selenium-independent glutathione peroxidase activity was not detectable. In conclusion, a biochemical gradient in glutathione-related antioxidant defences and thiobarbituric acid reactive substances proceeding from the proximal to the distal segments seems to exist in the normal rabbit aorta. These results could contribute to explain the non homogeneous distribution of experimental atherosclerosis in the rabbit aorta.     

Molecular modeling of the axial and circumferential elastic moduli of tubulin

Microtubules play a number of important mechanical roles in almost all cell types in nearly all major phylogenetic trees. We have used a molecular mechanics approach to perform tensile tests on individual tubulin monomers and determined values for the axial and circumferential moduli for all currently known complete sequences. The axial elastic moduli, in vacuo, were found to be 1.25 GPa and 1.34 GPa for α- and β-bovine tubulin monomers. In the circumferential direction, these moduli were 378 MPa for α- and 460 MPa for β-structures. Using bovine tubulin as a template, 269 homologous tubulin structures were also subjected to simulated tensile loads yielding an average axial elastic modulus of 1.10 ± 0.14 GPa for α-tubulin structures and 1.39 ± 0.68 GPa for β-tubulin. Circumferentially the α- and β-moduli were 936 ± 216 MPa and 658 ± 134 MPa, respectively. Our primary finding is that that the axial elastic modulus of tubulin diminishes as the length of the monomer increases. However, in the circumferential direction, no correlation exists. These predicted anisotropies and scale dependencies may assist in interpreting the macroscale behavior of microtubules during mitosis or cell growth. Additionally, an intergenomic approach to investigating the mechanical properties of proteins may provide a way to elucidate the evolutionary mechanical constraints imposed by nature upon individual subcellular components.     

Effect of residual stress and heterogeneity on circumferential stress in the arterial wall

Quantifying the stress distribution through the arterial wall is essential to studies of arterial growth and disease. Previous studies have shown that both residual stress, as measured by opening angle, and differing material properties for the media-intima and the adventitial layers affect the transmural circumferential stress (sigma theta) distribution. Because a lack of comprehensive data on a single species and artery has led to combinations from multiple sources, this study determined the sensitivity of sigma theta to published variations in both opening angle and layer thickness data. We fit material properties to previously published experimental data for pressure-diameter relations and opening angles of rabbit carotid artery, and predicted sigma theta through the arterial wall at physiologic conditions. Using a one-layer model, the ratio of sigma theta at the internal wall to the mean sigma theta decreased from 2.34 to 0.98 as the opening angle increased from 60 to 130 deg. In a two-layer model using a 95 deg opening angle, mean sigma theta in the adventitia increased (112 percent for 25 percent adventitia) and mean sigma theta in the media decreased (47 percent for 25 percent adventitia). These results suggest that both residual stress and wall layers have important effects on transmural stress distribution. Thus, experimental measurements of loading curves, opening angles, and wall composition from the same species and artery are needed to accurately predict the transmural stress distribution in the arterial wall.     

Biomechanical properties of the layered oesophagus and its remodelling in experimental type-1 diabetes

Passive biomechanical properties in term of the stress-strain relationship and the shear modulus were studied in separated muscle layer and mucosa-submucosa layer in the oesophagus of normal and STZ (streptozotocin)-induced diabetic rats. The mucosa-submucosa and muscle layers were separated using microsurgery and studied in vitro using a self-developed test machine. Stepwise elongation and inflation plus continuous twist were applied to the samples. A constitutive equation based on a strain energy function was used for the stress-strain analysis. Five material constants were obtained for both layers. The mucosa-submucosa layer was significantly stiffer than the muscle layer in longitudinal, circumferential and circumferential-longitudinal shear direction. The mechanical constants of the oesophagus show that the oesophageal wall was anisotropic, the stiffness in the longitudinal direction was higher than in the circumferential direction in the intact oesophagus (P < 0.001) and in the muscle layer (P < 0.05). Diabetes-induced pronounced increase in the outer perimeter, inner perimeter and lumen area in both the muscle and mucosa-submucosa layer. The growth of the mucosa-submucosa layer (P < 0.001) was more pronounced than the muscle layer (P < 0.05). Furthermore, the circumferential stiffness of the mucosa-submucosa layer increased 28 days after STZ treatment. In conclusion, the oesophagus is a non-homogeneous anisotropic tube. Thus, the mechanical properties differed between layers as well as in different directions. Morphological and biomechanical remodelling is prominent in the diabetic oesophagus.     

Origin of axial prestretch and residual stress in arteries

The structural protein elastin endows large arteries with unique biological functionality and mechanical integrity, hence its disorganization, fragmentation, or degradation can have important consequences on the progression and treatment of vascular diseases. There is, therefore, a need in arterial mechanics to move from materially uniform, phenomenological, constitutive relations for the wall to those that account for separate contributions of the primary structural constituents: elastin, fibrillar collagens, smooth muscle, and amorphous matrix. In this paper, we employ a recently proposed constrained mixture model of the arterial wall and show that prestretched elastin contributes significantly to both the retraction of arteries that is observed upon transection and the opening angle that follows the introduction of a radial cut in an unloaded segment. We also show that the transmural distributions of elastin and collagen, compressive stiffness of collagen, and smooth muscle tone play complementary roles. Axial prestresses and residual stresses in arteries contribute to the homeostatic state of stress in vivo as well as adaptations to perturbed loads, disease, or injury. Understanding better the development of and changes in wall stress due to individual extracellular matrix constituents thus promises to provide considerable clinically important insight into arterial health and disease.     

Nonuniformity of axial and circumferential remodeling of large coronary veins in response to ligation

The pressure-induced remodeling of coronary veins is important in coronary venous retroperfusion. Our hypothesis is that the response of the large coronary veins to pressure overload will depend on the degree of myocardial support. Eleven normal Yorkshire swine from either sex, weighing 31-39 kg, were studied. Five pigs underwent ligation of the left anterior descending (LAD) vein, and six served as sham-operated controls. The ligation of the coronary vein caused an increase in pressure intermediate to arterial and venous values. After 2 wk of ligation, the animals were euthanized and the coronary vessels were perfusion-fixed with glutaraldehyde. The LAD vein was sectioned, and detailed morphometric measurements were made along its length from the point of ligation near the base down to the apex of the heart. The structural remodeling of the vein was circumferentially nonuniform because the vein is partially embedded in the myocardium; it was also axially nonuniform because it is tethered to the myocardium to different degrees along its axial length. The wall area was significantly larger in the experimental group, whereas luminal area in the proximal LAD vein was significantly smaller in the same group compared with sham-operated controls. The wall thickness-to-radius ratio was also significantly larger in the experimental group in proportion to the increase in pressure. The major conclusion of this study is that the response of the vein depends on the local wall stress, which is, in part, determined by the surrounding tissue. Furthermore, the geometric remodeling of the coronary vein restores the circumferential stress to the homeostatic value.     

Regional distribution of the Na+ and K+ currents around the crystalline lens of rabbit

Early studies described asymmetricalelectrical properties across the ocular lens in theanterior-to-posterior direction. More recent results obtained with avibrating probe indicated that currents around the lens surface are notuniform by showing an outwardly directed K⁺ efflux at thelens equator and Na⁺ influx at the poles. The latterstudies have been used to support theoretical models for fluidrecirculation within the avascular lens. However, the existence of anonuniform current distribution in the lens epithelium from theanterior pole to the equator has never been confirmed. The present workdeveloped a modified short-circuiting technique to examine the netflows of Na⁺ and K⁺ across arbitrarily definedlens surface regions. Results indicate that passive inflows ofNa⁺ occur at both the anterior polar region and posteriorlens surface, consistent with suggestions derived from the vibratingprobe data, whereas K⁺ efflux plus theNa⁺-K⁺ pump-generated current comprise thecurrents at the equatorial surface and an area anterior to it.Furthermore, Na⁺-K⁺ pump activity was absent atthe posterior surface and its polar region in all lenses examined, aswell as from the anterior polar region in most lenses. The latterunexpected observation suggests that the monolayered epithelium, whichis confined to the anterior surface of the lens, does not express anactive Na⁺-K⁺ pump at its anterior-most aspect.Nevertheless, this report represents the first independent confirmationthat positive currents leave the lens around the equator and reenteracross the polar and posterior surfaces.

     

Regional distribution of pyroglutamyl peptidase II in rabbit brain, spinal cord, and organs.

Pyroglutamyl peptidase II (PPII) is a narrow specificity ectoenzyme that degrades thyrotropin-releasing hormone (TRH). We detected the enzyme in the brain of various mammals, with highest specific activity in rabbit brain. In this species, activity was heterogeneously distributed in the central nervous system. There was a 28-fold difference between regions of highest and lowest PPII activity. Enzyme activity was highest in the olfactory bulb and posterior cortex. In the spinal cord, activity was low but unevenly distributed, with highest values detected in the thoracic (T) region. Segments T1 and T2 activities were particularly high. Other organs contained low or undetectable levels of activity. The levels of TRH-like immunoreactivity (TRH-LI) in spinal cord segments were greatest in T3-T4 and lumbar L2-L6. Low concentrations were found in T1 and T9-T12. There was a partial correlation between the distribution of PPII activity and TRH receptors but not with TRH-LI levels. These results demonstrate that PPII is predominantly a central nervous system enzyme, and they support the hypothesis that PPII is responsible for degrading TRH released into the synaptic cleft.     

Determination of the axial and circumferential mechanical properties of the skin tissue using experimental testing and constitutive modeling

The skin, being a multi-layered material, is responsible for protecting the human body from the mechanical, bacterial, and viral insults. The skin tissue may display different mechanical properties according to the anatomical locations of a body. However, these mechanical properties in different anatomical regions and at different loading directions (axial and circumferential) of the mice body to date have not been determined. In this study, the axial and circumferential loads were imposed on the mice skin samples. The elastic modulus and maximum stress of the skin tissues were measured before the failure occurred. The nonlinear mechanical behavior of the skin tissues was also computationally investigated through a suitable constitutive equation. Hyperelastic material model was calibrated using the experimental data. Regardless of the anatomic locations of the mice body, the results revealed significantly different mechanical properties in the axial and circumferential directions and, consequently, the mice skin tissue behaves like a pure anisotropic material. The highest elastic modulus was observed in the back skin under the circumferential direction (6.67 MPa), while the lowest one was seen in the abdomen skin under circumferential loading (0.80 MPa). The Ogden material model was narrowly captured the nonlinear mechanical response of the skin at different loading directions. The results help to understand the isotropic/anisotropic mechanical behavior of the skin tissue at different anatomical locations. They also have implications for a diversity of disciplines, i.e., dermatology, cosmetics industry, clinical decision making, and clinical intervention.     

Strain distribution in the layered wall of the esophagus.

The function of the esophagus is to move food by peristaltic motion, which is the result of the interaction of the tissue forces in the esophageal wall and the hydrodynamic forces in the food bolus. To understand the tissue forces in the esophagus, it is necessary to know the zero-stress state of the esophagus, and the stress-strain relationships of the tissues. This article is addressed to the first topic: the representation of zero-stress state of the esophagus by the states of zero stress-resultant and zero bending moment of the mucosa-submucosa and the muscle layers. It is shown that at the states of zero stress-resultant and zero bending moment, these two layers are not tubes of smaller radii but are open sectors whose shapes are approximately cylindrical and more or less circular. When the sectors are approximated by circular sectors, we measured their radii, opening angles, and average thickness around the circumference. Data on the radii, thickness-to-radius ratios, and the opening angles of these sectors are presented. Knowing the zero-stress state of these two layers, we can compute the strain distribution in the wall at any in vivo state, as well as the residual strain in the esophageal wall at the no-load state. The results of the in vivo states are compared to those obtained by a conventional approach, which treats the esophageal wall as a homogeneous material, and to another popular simplification, which ignores the residual strains completely. It is shown that the errors caused by the homogeneous wall assumption are relatively minor, but those caused by ignoring the residual strains completely are severe.     

Substance P: Regional distribution and specific binding to synaptic membranes in rabbit central nervous system

Regional distribution of endogenous substance P and the specific [³H]substance P binding to synaptic membranes in rabbit central nervous system were investigated. The highest level of substance P was found in mesencephalon, followed by diencephalon, corpus striatum, hippocampus, pons-medulla and cortex. In spinal cord, much higher amount of substance P existed in dorsal half than in ventral half. Most of the substance P present in the areas enriched in substance P was located in crude mitochondrial P₂ fractions containing nerve endings. A saturable, high affinity, specific binding of [³H]substance P in synaptic membranes was found. The apparent maximal number of binding sites was 95.7 fmole/mg protein, while the dissociation constant (K_D) was 2.74 nM. The binding was displaced by substance P sequence fragments and the related peptides with relative potencies generally parallelizing their pharmacological activities. The distribution of such specific binding generally correlated with endogenous substance P. The presence of such binding sites for substance P in synaptic membranes suggests a possible role for substance P as a transmitter or modulator of neural function.     

The strain energy function in axial plant growth

A model for axial plant growth is formulated based on conservation of energy. The model derivation assumes that a strain energy function exists to describe the dissipation of potential energy associated with water uptake, mechanical deformation, and biosynthesis during growth. The derivation does not, however, make any further assumption on the mathematical form of this constitutive relation. The model is employed to investigate possible forms of the strain energy function as applied to steady root growth. Solutions of the nonlinear partial differential equations governing growth are given for cases when the third derivative of the strain energy function is >, <, or =0. These three cases encompass a multitude of mathematical forms of the strain energy function. The resulting solutions are compared with the realization of steady axial root growth. The results of this analysis indicate that a quadratic form of the strain energy function best described steady growth. This conclusion is consistent with previous assumptions on the form of constitutive relations for growth, and allows further interpretation on the water relations, mechanical, and biosynthetic energies associated with plant growth.Research support provided by state and federal funds appropriated to the OSU/OARDC. Journal article no. 12–88     

Compressive axial strain distributions in cancellous bone specimens

The compressive axial strain distribution in cylindrical trabecular bone specimens was studied using digitized images of the specimen surface. Specimens were tested with strain rate 0.00015 s-1. Images were taken at 0, 1, 2, 3, 4, 6, 8 and 10% strain. Using an optical illusion of movement by rapidly changing succeeding images, failures were classified as transverse (33%) or oblique collapses (67%). The location of failure was not determined by the specimen density gradient. Local axial strain in the distal, intermediate and proximal third was measured throughout the compression in the transversely failing specimens, whereas local strain in the obliquely failing specimens was measured in the pre-failure phase only. Axial strain inhomogeneity was observed in the pre-failure as well as in the post-failure phase. In the pre-failure phase the intermediate third was strained significantly less than the thirds near the ends. In the post-failure phase specimen strain occurred solely in the collapsed part. Ultimate strain of the transversely failing specimens was 2.5% and ultimate strain of the failing third was 3.7%. At failure less than 1% strain was observed in the intermediate third and at 10% specimen strain 1.5% local strain was found in the intermediate third. The results indicate unreliability of conventional stiffness and strain measurements in trabecular bone specimens probably due to lack of trabecular constraint at the end surfaces. Conventional measurements tend to underestimate stiffness and, by giving an average value of strain in spite of considerable strain inhomogeneity, to underestimate failure strain.     

Hypoblast controls mesoderm generation and axial patterning in the gastrulating rabbit embryo

Gastrulation in higher vertebrate species classically commences with the generation of mesoderm cells in the primitive streak by epithelio-mesenchymal transformation of epiblast cells. However, the primitive streak also marks, with its longitudinal orientation in the posterior part of the conceptus, the anterior-posterior (or head-tail) axis of the embryo. Results obtained in chick and mouse suggest that signals secreted by the hypoblast (or visceral endoderm), the extraembryonic tissue covering the epiblast ventrally, antagonise the mesoderm induction cascade in the anterior part of the epiblast and thereby restrict streak development to the posterior pole (and possibly initiate head development anteriorly). In this paper we took advantage of the disc-shape morphology of the rabbit gastrula for defining the expression compartments of the signalling molecules Cerberus and Dickkopf at pre-gastrulation and early gastrulation stages in a mammal other than the mouse. The two molecules are expressed in novel expression compartments in a complementary fashion both in the hypoblast and in the emerging primitive streak. In loss-of-function experiments, carried out in a New-type culturing system, hypoblast was removed prior to culture at defined stages before and at the beginning of gastrulation. The epiblast shows a stage-dependent and topographically restricted susceptibility to express Brachyury, a T-box gene pivotal for mesoderm formation, and to transform into (histologically proven) mesoderm. These results confirm for the mammalian embryo that the anterior-posterior axis of the conceptus is formed first as a molecular prepattern in the hypoblast and then irrevocably fixed, under the control of signals secreted from the hypoblast, by epithelio-mesenchymal transformation (primitive streak formation) in the epiblast.Edited by D. Tautz