A molecular basis for elastic tissue degeneration in pulmonary and vascular disease.
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In osteoarthritis, one postulate is that changes in the mechanical properties of the subchondral bone layer result in cartilage damage. The goal of this study was to examine changes in subchondral trabecular bone properties at the calcified tissue level in the early stages of cartilage damage. Finite element models were constructed from microCT scans of trabectilar bone from the proximal tibia of donors with mild cartilage damage and from normal donors. In the donors with cartilage damage, macroscopic damage was present only in the medial compartment. The effective tissue elastic moduli were determined using a combination of finite element models and mechanical testing. The bone tissue modulus was reduced by 60% in the medial condyle of the cases with cartilage damage compared to the control specimens. Neither the presence of cartilage damage nor the anatomic site (medial vs. lateral) affected the elastic modulus at the apparent level. The volume fraction of trabecular bone was higher in the medial compartment compared to the lateral compartment of tibiae with cartilage damage (but not the controls), suggesting that mechanical properties were preserved in part at the apparent level by an increase in the bone volume fraction. It seems likely that the normal equilibrium between cartilage properties, bone tissue properties and bone volume fraction is disrupted early in the development of osteoarthritis.
This is an investigation into the prognostic factors of 117 patients with spontaneous normo- and hypertensive intracerebral haematomas, supported by animal experiments. Preserved tissue elastance and fluid conduction enables the drainage of intrinsic haematoma serum into the CSF spaces in normotensive patients, who showed an increased extension of a perifocal hypodensity in the CT. Arterial hypertension decreased the possibility of fluid resolution. Our experimental studies showed that in hypertensive cases the serum remained trapped in the haematoma, which explains the small hypodense area around the haematoma in most of the hypertensive cases. If as an exception in hypertensives of perifocal hypodensity develops then it acts as additional space-occupying factor. Corresponding observations were made in hypertensive animals which showed a reduced serum movement out of the haematoma, but an increased Evans-Blue content in the perifocal tissue. Both pathological mechanisms explain the poorer prognosis in patients with intracerebral haematomas associated with high arterial blood pressure.
We have observed striking differences in the mechanical properties of airway smooth muscle preparations among different species. In this study, we provide a novel analysis on the influence of tissue elastance on smooth muscle shortening using previously published data from our laboratory. We have found that isolated human airways exhibit substantial passive tension in contrast to airways from the dog and pig, which exhibit little passive tension (<5% of maximal active force versus approximately 60% for human bronchi). In the dog and pig, airway preparations shorten up to 70% from Lmax (the length at which maximal active force occurs), whereas human airways shorten by only approximately 12% from Lmax. Isolated airways from the rabbit exhibit relatively low passive tension (approximately 22% Fmax) and shorten by 60% from Lmax. Morphologic evaluation of airway cross sections revealed that 25-35% of the airway wall is muscle in canine, porcine, and rabbit airways in contrast to approximately 9% in human airway preparations. We postulate that the large passive tension needed to stretch the muscle to Lmax reflects the high connective tissue content surrounding the smooth muscle, which limits shortening during smooth muscle contraction by imposing an elastic load, as well as by causing radial constraint.
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Ascaris suum (AS) challenge in nonhuman primates is used as an animal model of human asthma. The primary goal of this study was to determine whether the airways and respiratory tissues in monkeys that are bronchoconstricted by AS inhalation behave similarly to those in asthmatic humans. Airway resistance (Raw) and tissue elastance (Eti) were estimated from respiratory system input (Zin) or transfer (Ztr) impedance. Zin (0.4-20 Hz) and Ztr (2-128 Hz) were measured in anesthetized cynomolgus monkeys (n = 10) under baseline (BL) and post-AS challenge conditions. Our results indicate that AS challenge in monkeys produces 1) predominantly an increase in Raw and not tissue resistance, 2) airway wall shunting at higher AS doses, and 3) heterogeneous airway constriction resulting in a decrease of lung parenchyma effective compliance. We investigated whether the airway and tissue properties estimated from Zin and Ztr were similar and found that Raw estimated from Zin and Ztr were correlated [r(2) = 0.76], not significantly different at BL (13.6 +/- 1.4 and 13.1 +/- 0.9 cmH(2)O. l(-1). s(-1), respectively), but significantly different post-AS (20.5 +/- 4.5 cmH(2)O. l(-1). s(-1) and 18.5 +/- 5.2 cmH(2)O. l(-1). s(-1)). There was no correlation between Eti estimated from Zin and Ztr. The changes in lung mechanical properties in AS-bronchoconstricted monkeys are similar to those recently reported in human asthma, confirming that this is a reasonable model of human asthma.
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Elastic fibres have been generally considered to play no significant role in the mechanical functioning of the intervertebral disc since earlier studies reported that the elastic fibre network was sparse and irregular. However, a recent study has reported that the network is highly organized and that the distribution and orientation of elastic fibres varies from region to region. In the annulus, elastic fibres appear densely distributed in the region between the lamellae and also in 'bridges' across the lamellae. They are also organized in the nucleus where long straight fibres are radially oriented and anchor perpendicularly or obliquely into the cartilaginous endplate. Immunohistochemistry using specific antibodies indicates that elastin is present in the network, as is fibrillin. Biochemical studies show, however, that the amino acid composition of the residue remaining after alkaline (NaOH) extraction or CNBr digestion contains a higher concentration of polar amino acids than ligamentum nuchal elastin. The composition of the residue suggests that disc elastin may cross-link strongly with some other matrix components. With such coupling, it is thought that elastic fibres could play a significant mechanical role even though overall elastin is less than 5% of the total dry weight of the disc.
Thirty human aortas with varying degrees of atheroma graded macroscopically according to the WHO classification were taken at autopsy from subjects of different ages (24-86 years). Study by light microscopy showed aortas with an intact wall (4 subjects, 25-46 years) with a thin intima and regular elastic layers, and aortas with varying degrees of modification of the wall, where the intima was of varying thickness and the elastic fibers showed varying degrees of damage (moderate lesions: 5 subjects, 35-52 yrs; severe lesions: 21 subjects, 26-86 yrs). From each aorta, a 4-cm segment from the tunica media, free of atheromatous lesions, was defatted and subjected to successive treatment with EDTA-Tris, 6 M guanidine-HCl-Tris, 6 M guanidine-HCl-Tris-DTE and collagenase. The residues (EP residues) were subjected to amino acid (AA) analysis and transmission electron microscopy (TEM) study. In the young subject, the AA composition was similar to that of elastin and the TEM images were characteristic of this substance. In the aging subject, an increase in polar AA and a parallel decrease in apolar AA and crosslinks was noted. By TEM, the elastin was seen to be associated with abundant fibrillar material. Trypsin treatment of EP residues gave E residues, whose composition and TEM appearance were similar in all samples, corresponding to the standard composition of elastin and its classic appearance by electron microscopy. We suggest that the fibrillar material removed by trypsin is the morphological reflection of the chemical variations observed in the EP residues. These correspond to contamination of the elastin by a polar protein fraction. This contamination is closely correlated with age but not with the degree of atheroma. Thus the age-related chemical changes in elastin appear to be independent of the onset and evolution of atheromatous lesions. The 10-15 nm diameter of the contaminating fibrillar material suggests that may be the microfibrillar fraction of elastic tissue.
Accurate clinical interpretation of the sound velocity derived from axial transmission devices requires a detailed understanding of the propagation phenomena involved and of the bone factors that have an impact on measurements. In the low megahertz range, ultrasonic propagation in cortical bone depends on anisotropic elastic tissue properties, porosity and the cortical geometry (e.g., thickness). We investigated 10 human radius samples from a previous biaxial transmission study using a 50-MHz scanning acoustic microscope (SAM) and synchrotron radiation microcomputed tomography. The relationships between low-frequency axial transmission sound speed at 1 and 2 MHz, structural properties (cortical width Ct.Wi, porosity, Haversian canal density and material properties (acoustic impedance, mineral density) on site-matched cross-sections were investigated. Significant linear multivariate regression models (1 MHz: R(2) = 0.84, p < 10(-4), root-mean-square error (RMSE) = 38 m/s, 2 MHz: R(2) = 0.65, p < 10(-4), RMSE = 48 m/s) were found for the combination of Ct.Wi with porosity and impedance. A new model was derived that accounts for the nonlinear dispersion relation with Ct.Wi and predicts axial transmission velocities measured at different ultrasonic frequencies (R(2) = 0.69, p < 10(-4), RMSE = 52 m/s).
The elastic properties of the lung-thorax-system were studied in a group of rats treated with prednisolone and D-penicillamine and in a control group, after the surfactant had been washed out. Prednisolone given for 30 days i.p. seemed to make lung parenchyma more stiff-similar to what happens to skin. D-penicillamine has no influence on the lung tissue elasticity (compliance, residual volume, homogenity of inflation) but the elastic retraction after maximal inflation is significantly reduced compared with the control group or the Prednisolone treated group.
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