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Transmural sheet strains in the lateral wall of the ovine left ventricle.

In an attempt to provide a better understanding of our finding that regions with contracting left ventricular myofibers need not develop a significant transmural systolic wall thickening gradient, the analytic approach of Costa et al. was applied to the four-dimensional dynamic data obtained 1 and 8 wk after surgical implantation of transmural radiopaque beads in the lateral equatorial left ventricular wall in seven ovine hearts. Quantitative histology of tissue blocks demonstrated that fiber angles varied linearly across the wall in this region from -37 degrees in the subepicardium to +18 degrees in the subendocardium. Sheet angles exhibited a pleated-sheet behavior, alternating sign from subepicardium to subendocardium. From end diastole (reference configuration) to end systole (deformed configuration), fiber strain was uniformly negative, sheet extension and sheet thickening were uniformly positive, and sheet-normal shear contributed to wall thickening at all wall depths. Subepicardial radial wall thickening increased significantly from week 1 to week 8, with significant increases in the contributions from subepicardial sheet extension and sheet-normal shear. At 1 and 8 wk, the contribution of sheet-normal shear to wall thickening was substantial at all transmural depths; the contribution of sheet extension to wall thickening was greatest in the subepicardium and least in the subendocardium, and the contribution of sheet thickening to wall thickening was greatest in the subendocardium and least in the subepicardium. A mechanistic model is proposed that provides a working hypothesis that a selective decrease in subepicardial intercellular matrix stiffness is responsible for elimination of the transmural wall thickening gradient 1-8 wk after marker implantation surgery.

Adaptation, Physiological↗

Vibrational characteristics of carbon nanotubes as nanomechanical resonators.

Using eigenvalue analysis of mass and stiffness matrices directly computed from atomistic simulations, natural frequencies and mode shapes of various carbon nanotubes are studied. The stiffness matrix was developed from the Tersoff-Brenner potential for carbon-carbon interactions. The computed frequencies of the radial breathing modes of a variety of armchair (n, n) nanotubes agree well with results obtained by others using different techniques. In addition, the study reveals diverse mode shapes such as accordion-like axial modes, lateral bending modes, torsional modes, axial shear modes, and radial breathing modes for a variety of single-wall, multi-wall, and bamboo-type carbon nanotubes. The effects of different constraints on the carbon nanotube ends on the computed frequencies and mode shapes have been investigated for possible applications in vibration sensors or electromechanical resonators.

Computer Simulation↗

Fast finite elements for surgery simulation.

This paper discusses volumetric deformable models for modeling human body parts and organs in surgery simulation systems. These models are built using finite element models of linear elastic materials. To achieve real-time response condensation has been applied to the system stiffness matrix, and selective matrix vector multiplication has been used to minimize the computational cost.

Algorithms↗

Interactive haptic modeling of colon and colonoscope.

This paper presents physics-based modeling for colonoscopy training simulator. The colon is modeled as a chain of beam along the medial axis for global bending motions. The Timoshenko's beam theory is applied to the centerline of colon extracted from a medical image. The stiffness matrix of colon is formulated using the finite element method. The colonoscope model consists of rigid elements connected with torsional spring and damper. This modeling allows global bending motions to be simulated in real time.

Colon↗

Enhanced pre-computed finite element models for surgical simulation.

Soft tissue modeling is an important component in effective surgical simulation systems. A pre-computed finite element method based on elastic models is well suited to modeling soft tissue deformation. This paper addresses two principal issues: the flexibility of the pre-computed FE method and the approximation approach to non-linear elastic models. We describe a dynamic mechanism of the reconfiguration of the contacted nodes and the fixed boundary, without re-computing the inverse of the global stiffness matrix. The flexibility of the pre-computed models is described for both linear and non-linear elastic models.

Canada↗

Evaluation of the effect of preload force on resonance frequencies for a traveling wave ultrasonic motor.

In this paper, a novel method of numerical computation of the natural frequencies, depending on the most important running parameters for an ultrasonic motor, is described. The analyzed configuration by the Space Division of Alenia Spazio, Rome, within an Italian Space Agency (ASI) development program, is the flexural traveling wave one. The dynamic equations for the stator and the rotors of the ultrasonic motor are assumed into a differential system, whose equations are coupled by terms that represent interface generalized forces. In order to calculate natural frequencies of the motor-coupled terms of the equations are worked out with respect to the variables of the degrees of freedom. Hence, the mass, damping, and stiffness matrix for the whole system are obtained, then resonance frequencies, depending on the most important running parameters such as axial preload of the motor, are calculated. The results are compared with numerical ones, obtained by a finite element modeling (FEM) model, showing a good agreement.

Journal Article↗

Arterial stiffness and extracellular matrix.

The growing prevalence and associated risk of arterial stiffness provide a major challenge to better understand the underlying causes and the resultant physiological impact of this condition. Structural components within the arterial wall, mainly collagen and elastin, are considered to be major determinants of arterial stiffness. Thus, quantitative and qualitative alterations of collagen and elastin fibers are involved in arterial stiffening that is associated with the aging process and disease states such as hypertension, diabetes, atherosclerosis, and chronic renal failure. Elucidation of mechanisms leading to the above alterations will aid in more specifically targeted therapeutic interventions because currently available cardiovascular medications fall short at reducing the stiffness of the large arteries. Reduction of arterial stiffness will likely have a significant impact on morbidity and mortality of older adults, as well as subjects suffering from cardiovascular and renal diseases.

Animals↗

[Molecular and cellular determinants of arterial stiffness: role of cell-matrix connections].

Increased large artery stiffness is believed to be a cardiovascular risk factor independent from mean arterial pressure. The mechanical properties of large arteries depend not only on the amounts of their main constituents (elastin, collagen, and smooth muscle cells) but also on the spatial organization and mechanical interactions among these components. These interactions may be mediated by extracellular matrix adhesion proteins and their membrane receptors or integrins. From a mechanical viewpoint, a key element may be the dense plaque, which is composed of cytoskeletal proteins linked to matrix proteins via membrane integrin receptors. Integrin expression in normal and diseased blood vessels is currently the focus of active research. In humans, hypertension-related arterial hypertrophy is not associated with an increase in intrinsic arterial wall stiffness. Aortic fibronectin expression is increased in spontaneously hypertensive rats (SHRs). By increasing cell-matrix anchoring, fibronectin may contribute to protect arterial wall components from the increased mechanical loads associated with hypertension. In atherosclerosis, the increase in cell-matrix anchoring plays a key role in preventing atheroma plaque rupture. To determine the exact role of adhesion molecules in arterial stiffness, there is a need for studies involving use of specific anti-integrin agents and of transgenic animal models.

Animals↗

Modeling of wave propagation in layered piezoelectric media by a recursive asymptotic method.

In this paper, a simple asymptotic method to compute wave propagation in a multilayered general anisotropic piezoelectric medium is discussed. The method is based on explicit second and higher order asymptotic representations of the transfer and stiffness matrices for a thin piezoelectric layer. Different orders of the asymptotic expansion are obtained using Padé approximation of the transfer matrix exponent. The total transfer and stiffness matrices for thick layers or multilayers are calculated with high precision by subdividing them into thin sublayers and combining recursively the thin layer transfer and stiffness matrices. The rate of convergence to the exact solution is the same for both transfer and stiffness matrices; however, it is shown that the growth rate of the round-off error with the number of recursive operations for the stiffness matrix is twice that for the transfer matrix; and the stiffness matrix method has better performance for a thick layer. To combine the advantages of both methods, a hybrid method which uses the transfer matrix for the thin layer and the stiffness matrix for the thick layer is proposed. It is shown that the hybrid method has the same stability as the stiffness matrix method and the same round-off error as the transfer matrix method. The method converges to the exact transfer/stiffness matrices essentially with the precision of the computer round-off error. To apply the method to a semispace substrate, the substrate was replaced by an artificial perfect matching layer. The computational results for such an equivalent system are identical with those for the actual system. In our computational experiments, we have found that the advantage of the asymptotic method is its simplicity and efficiency.

Journal Article↗

Dynamic compression of chondrocyte-seeded fibrin gels: effects on matrix accumulation and mechanical stiffness.

OBJECTIVE: Various strategies have been tested to direct and control matrix synthesis in tissue engineered cartilage, including mechanical stimulation of the construct both before and after implantation. This study examined the effects of oscillatory compression on chondrocytes in a fibrin-based tissue engineered cartilage. DESIGN: Chondrocyte-seeded fibrin gels were cultured under unconfined mechanical compression for 10 or 20 days (free-swelling, 10% static, or 10+/-4% at 0.1 or 1Hz). During the culture period, accumulation of nitrite, sGAG, and proteolytic enzymes in the culture media were monitored. Following culture, the mechanical stiffness and biochemical content of the gels (DNA, sGAG, and hydroxyproline content and GAG Delta-disaccharide composition) were assessed. RESULTS: Compared to free-swelling conditions, static compression had little effect on the mechanical stiffness or biochemical content of the gels. Compared to static compression, oscillatory compression produced softer gels, inhibited sGAG and hydroxyproline accumulation in the gels, and stimulated accumulation of nitrite and sGAG in the culture media. Minimal differences were observed in DNA content and Delta-disaccharide composition across treatment conditions. CONCLUSIONS: In this study, oscillatory compression inhibited formation of cartilage-like tissues by chondrocytes in fibrin gels. These results suggest that the effects of mechanical stimuli on tissue engineered cartilage may vary substantially between different scaffold systems.

Animals↗

The effects of acetone, ethanol, HEMA, and air on the stiffness of human decalcified dentin matrix.

During resin-bonding procedures, dentin surfaces are treated with acidic conditioners to remove the smear layer and decalcify the surface to expose the collagen fibrils of the underlying matrix. These decalcified surfaces are then either air-dried or treated with dehydrating solvents, procedures which may modify the physical properties of the dentin matrix. The purpose of this study was to evaluate the effects of dehydration on the stiffness of the decalcified dentin matrix. Small (8 x 1.7 x 0.9 mm) beams of dentin were prepared from mid-coronal dentin of extracted human molars. The ends were covered with varnish for protection, and the specimens were placed in 0.5 M EDTA for 5 days to decalcify. The stiffness was measured by both the cantilever technique and by conventional stress-strain testing. Specimens tested by the cantilever technique were sequentially exposed to water, acetone, alcohol, HEMA, and glutaraldehyde. Specimens tested by conventional stress-strain testing were exposed either to water, acetone, or HEMA, or were allowed to air-dry. The results indicate that the stiffness of decalcified human dentin matrix is very low (ca. 7 MPa), if the specimens are wet with water. As they are dehydrated, either chemically in water-miscible organic solvents or physically in air, the stiffness increases 20- to 38-fold at low strains or three- to six-fold at high strains. These increases in modulus were rapidly reversed by rehydration in water. Exposure to glutaraldehyde also produced an increase in stiffness that was not reversible when the specimens were placed back in water.

Acetone↗

Inhibition of angiogenesis on glycated collagen lattices.

Advanced glycation endproduct (AGE) accumulation in extracellular matrix proteins has been demonstrated in diabetic patients with a significant correlation with the severity of diabetic complications. AGE accumulation induces matrix protein cross-link formation, resulting in an increased stiffness of matrix fibres and the reduction of the susceptibility of matrix proteins to proteolytic degradation. We examined whether glycation-induced collagen cross-linking may affect vascular endothelial cell behaviours such as invasion, proliferation and differentiation, using the in vitro angiogenesis model of capillary-like structure formation in three-dimensional matrices of collagen type I. Endothelial cells cultured on collagen gel with angiogenic factors (the combination of fibroblast growth factor-2 and vascular endothelial growth factor) invaded the underlying collagen matrix, and organized capillary-like cord structures in the gel. We found that endothelial cell invasion into glycated collagen gel was significantly attenuated without any effect on proteinase activity including cell-associated plasminogen activator and matrix metalloproteinase in the conditioned medium. In addition, subsequent capillary-like cord formation was also inhibited in glycated collagen gel. In contrast, endothelial cell proliferation was enhanced on glycated collagen gel with or without angiogenic factors compared with control collagen gel. These results suggest that the structural alterations of extracellular matrix proteins through the glycation-induced cross-link formation affect the interaction between endothelial cell and extracellular matrix, resulting in the impairment of an adequate neovascularization in diabetic patients.

Angiogenesis Inducing Agents↗

Cellular and matrix contributions to tissue construct stiffness increase with cellular concentration.

The mechanics of bio-artificial tissue constructs result from active and passive contributions of cells and extracellular matrix (ECM). We delineated these for a fibroblast-populated matrix (FPM) consisting of chick embryo fibroblast cells in a type I collagen ECM through mechanical testing, mechanical modeling, and selective biochemical elimination of tissue components. From a series of relaxation tests, we found that contributions to overall tissue mechanics from both cells and ECM increase exponentially with the cell concentration. The force responses in these relaxation tests exhibited a logarithmic decay over the 3600 second test duration. The amplitudes of these responses were nearly linear with the amplitude of the applied stretch. The active component of cellular forces rose dramatically for FPMs containing higher cell concentrations.

Animals↗

Collagen metabolism in extracellular matrix may be involved in arterial stiffness in older hypertensive patients with left ventricular hypertrophy.

Collagen metabolism in the extracellular matrix (ECM) is related to the pathogenesis of cardiovascular stiffness and remodeling in hypertension. We evaluated the association between collagen metabolism markers and the newly developed parameter, brachial-ankle pulse wave velocity (baPWV), in older hypertensive patients with left ventricular hypertrophy (LVH). We performed echocardiography and baPWV measurement using a new device, form PWV/ABI (Colin Medical Technology, Komaki, Japan), and measured plasma levels of markers of collagen metabolism such as procollagen type I C-terminal propeptide (PICP: a marker of collagen synthesis), collagen type I pyridinoline cross-linked C-terminal telopeptide (ICTP: a marker of collagen type I degradation), matrix metalloproteinase-1 (MMP-1: a marker of collagen degradation) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in 46 hypertensive patients with LVH. BaPWV was correlated with the plasma level of PICP (r=0.33, p=0.03) and ICTP (r=0.29, p=0.05) and the total TIMP-1/MMP-1 ratio (an index of collagen turnover; r=0.30, p=0.04). BaPWV was negatively correlated with the E/A ratio of left ventricular inflow (r=-0.36, p<0.05), while baPWV was not correlated with left ventricular mass index (LVMI; r=-0.175, p=0.25) or deceleration time of the mitral E wave (DCT; r=0.15, p=0.31). The measures of hypertensive heart disease, such as the E/A ratio, DCT or LVMI were not correlated with any collagen markers in this study. In multiple regression analysis adjusted for confounding factors such as age, sex, pulse pressure, mean blood pressure, pulse rate, LVMI, E/A ratio and DCT, the positive correlation between baPWV and total TIMP-1/MMP-1 ratio remained significant (p<0.05). In conclusion, arterial stiffness in high-risk older hypertensive patients may involve ECM collagen metabolism.

Aged↗

Internal dynamics and protein-matrix coupling in trehalose-coated proteins.

We review recent studies on the role played by non-liquid, water-containing matrices on the dynamics and structure of embedded proteins. Two proteins were studied, in water-trehalose matrices: a water-soluble protein (carboxy derivative of horse heart myoglobin) and a membrane protein (reaction centre from Rhodobacter sphaeroides). Several experimental techniques were used: Mossbauer spectroscopy, elastic neutron scattering, FTIR spectroscopy, CO recombination after flash photolysis in carboxy-myoglobin, kinetic optical absorption spectroscopy following pulsed and continuous photoexcitation in Q(B) containing or Q(B) deprived reaction centre from R. sphaeroides. Experimental results, together with the outcome of molecular dynamics simulations, concurred to give a picture of how water-containing matrices control the internal dynamics of the embedded proteins. This occurs, in particular, via the formation of hydrogen bond networks that anchor the protein surface to the surrounding matrix, whose stiffness increases by lowering the sample water content. In the conclusion section, we also briefly speculate on how the protein-matrix interactions observed in our samples may shed light on the protein-solvent coupling also in liquid aqueous solutions.

Computer Simulation↗

Effects of the angiotensin receptor blocker candesartan on arterial stiffness and markers of extracellular matrix metabolism in patients with essential hypertension.

Laboratory studies have shown that angiotensin receptor blockers (ARBs) can affect extracellular matrix (ECM) metabolism and thereby have a beneficial effect on vascular remodeling. The aim of this study was to examine the clinical effects of the ARB candesartan cilexetil on serum markers of synthesis and degradation of ECM, as well as their relation to changes in arterial stiffness in hypertensive patients. Twenty-three patients with essential hypertension were recruited for this study. Markers related to ECM synthesis and degradation (procollagen type 1 propeptide [PIP], procollagen type III propeptide [PIIIP], matrix metalloproteinase-3 [MMP-3, stromelysin-1], tissue inhibitor of matrix metalloproteinases [TIMP-1], and hyaluronic acid [HA]) were examined both before and after one year of treatment with candesartan. Pulse-wave velocity [PWV] and ankle-brachial pressure index [ABI] were measured two months (i.e., after achieving blood pressure reduction) and one year after the initiation of therapy. PWV values after one year of treatment with ARB were significantly decreased compared to previous values, whereas ABI values were unchanged. Treatment with ARB was also associated with a significant decrease in serum PIIIP values and an increase in serum stromelysin-1, whereas changes in PIP, TIMP-1, and HA did not achieve statistical significance. A significant relationship was found between the changes in PWV and the changes in stromelysin-1 levels after correction for blood pressure and heart rate (p = 0.02). These results suggest that the treatment for just one year with ARB results in significant changes in markers of ECM metabolism as well as PWV. These effects on ECM metabolism could have a beneficial effect in decreasing vascular pathology in patients with essential hypertension.

Angiotensin II Type 1 Receptor Blockers↗

Localized stresses in the intervertebral disc resulting from a loose fragment. A theory for fissure and fragment.

STUDY DESIGN: A theoretical analysis of estimate the stresses generated in the anulus fibrosus by a loose fragment. OBJECTIVES: To test the hypothesis that a fragment can generate stress concentrations in an intervertebral disc that could lead to the progression of a fissure, and to provide a theoretical foundation for the laboratory model of lumbar disc protrusion, which proposes that a fragment is formed first and that prolapse is the final event of a chronic process. SUMMARY OF BACKGROUND DATA: A laboratory model was developed by Brinckmann and Porter in 1994, which indicated that introducing a fragment into an otherwise intact disc resulted in rapid failure of the disc under physiologic loads and flexion. Identical in vitro surgery with no reintroduction of fragments did not result in failure. METHODS: A theoretical model was developed in which a spherical fragment was impressed against a plane surface, representing the inner surface of the anulus. The stiffness of the sphere and that of the surface were varied, and the stresses generated in the anulus were calculated as a function of applied load. RESULTS: The contact stress and the shear stress increased as the stiffness of the fragment approached and exceeded that of the matrix. Increases in stiffness to more than four times that of the matrix resulted in little further increase in stress. Peak shear stresses are developed in the bulk matrix beyond the point of contact between the fragment and the anulus. For relatively small forces on the fragment, these stresses were comparable with those found in diarthrodial joints. CONCLUSIONS: It is shown that a fragment in an intervertebral disc produces localized areas of increased stress. Fatigue over long periods at these stresses could result in fissuring and premature failure of the tissue.

Humans↗

Time-varying mechanical behavior of multijointed arm in man.

1. The aim of this study was to describe the time-varying changes in the mechanical parameters of a multijointed limb. The parameters we considered are the coefficients of stiffness, viscosity, and inertia. Continuous pseudorandom perturbations were applied at the elbow joint during a catching task. A modified version of an ensemble technique was used for the identification of time-varying parameters. Torques at the elbow and wrist joints were then modeled with a linear combination of the changes in angular position and velocity weighted by the matrix of angular stiffness and the matrix of angular viscosity, respectively. Control experiments were also performed that involved the stationary maintenance of a given limb posture by resisting actively the applied perturbations. Different limb postures were examined in each such experiment to investigate the dependence of the mechanical parameters on limb geometry. 2. The technique for the identification of limb mechanical parameters proved adequate. The input perturbations applied at the elbow joint elicited angular oscillations at the wrist essentially uncorrelated with those produced at the elbow. The frequency of oscillation is much higher at the wrist than at the elbow, mainly because of the smaller inertia. The variance accounted for by the model was approximately 80% under both stationary and time-varying conditions; in the latter case the value did not vary significantly throughout the task. In addition, the model predicted values of the inertial parameters that were close to the anthropometric measures, and it reproduced the stepwise increase in limb inertia that occurs at the time the ball is held in the hand. 3. The values of angular stiffness and viscosity estimated under stationary conditions did not vary significantly with joint angle, in agreement with previous results obtained under quasi-static postural conditions. The matrix of the coefficients of angular stiffness was not symmetrical, indicating a prominent role for nonautogenic reflex feedbacks with unequal gains for elbow and wrist muscles. 4. A complex temporal modulation of angular stiffness and viscosity was observed during the catching task. The changes in the direct coefficients of angular stiffness tended to covary with those in the coupling coefficients from trial start up to approximately 30 ms before impact time. Around impact time, however, there was a complete dissociation: the direct terms peaked, whereas the coupling terms dropped. The direct terms of angular viscosity also increased before impact, whereas the viscosity coupling terms remained close to zero throughout.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗