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Calcium-activated potassium channels and NO regulate human peripheral conduit artery mechanics.

The role of NO in the regulation of the mechanical properties of conduit arteries is controversial in humans, and the involvement of an endothelium-derived hyperpolarizing factor (EDHF), acting through calcium-activated potassium (KCa) channels, has never been investigated at this level in vivo. We assessed in healthy volunteers, after oral administration of aspirin (500 mg), the effect of local infusion of NG-monomethyl-L-arginine (L-NMMA; 8 mumol/min for 8 minutes), an NO synthase inhibitor, tetraethylammonium chloride (TEA; 9 mumol/min for 8 minutes), a KCa channels inhibitor, and the combination of both on radial artery internal diameter, wall thickness (echo tracking), blood flow (Doppler), and pressure. The incremental elastic modulus and compliance were fitted as functions of midwall stress. L-NMMA decreased modulus and increased compliance at high levels of midwall stress (all P<0.05) without affecting radial diameter. TEA reduced radial diameter from 2.68+/-0.07 to 2.50+/-0.08 10(-3) m, increased the modulus, and decreased the compliance at all levels of stress (all P<0.05). Combination of both inhibitors synergistically enhanced the increase in modulus, the decrease in diameter (from 2.71+/-0.10 to 2.42+/-0.09 10(-3) m), and compliance compared with TEA alone (all P<0.05). These results confirm that inhibition of NO synthesis is associated with a paradoxical isometric smooth muscle relaxation of the radial artery. They demonstrate the involvement of KCa channels in the regulation of the mechanical properties of peripheral conduit arteries, supporting a role for EDHF at this level in vivo. Moreover, the synergistic effect of l-NMMA and TEA shows that KCa channels compensate for the loss of NO synthesis to maintain peripheral conduit artery diameter and mechanics.

Adult↗

Periodic fluid extrusion and models of digesta mixing in the intestine of a herbivore, the common brushtail possum (Trichosurus vulpecula).

The digesta in four gut compartments (proximal and distal halves of small intestine, caecum, and proximal colon) of a wild hindgut fermenting herbivore, the common brushtail possum (Trichosurus vulpecula), were investigated by rheometry and permeametry. Digesta from all compartments were highly viscous and exhibited shear-thinning. Apparent viscosity was positively related to dry matter content, and increased from proximal small intestine to colon. Dynamic rheological measurements showed that in small intestinal digesta the elastic modulus was greater than the viscous modulus and their ratios were characteristic of weak gels, indicating that digesta could sustain compression. The apparent viscosity of distal small intestinal digesta was markedly lower when measured by capillary viscometry than by rotatory viscometry, indicating that plug flow was likely to be facilitated by lubrication from a peripheral layer of less viscous fluid; i.e., there was an augmented plug flow. Permeametry showed that fluid was extruded from all digesta on compression at physiological pressures, that there was significant permeability of proximal and distal small intestinal digesta, but that digesta became progressively compacted during permeation, with a concomitant reduction in permeability as dry matter content increased. It is proposed that conditions within the small intestine differ from those of an ideal plug flow reactor as radial mixing and turbulence cannot occur. Instead, we suggest that segmentation and peristalsis aid radial mixing of the fluid phase by compressing the solid phase, with extrusion of fluid through the digesta plug. This extrusion may be followed by resorption of fluid back into the plug when the elasticity of the solid phase of digesta is Hookean, thus aiding the mixing of secreted enzymes with insoluble substrates within the plug.

Animals↗

Chronic inflammation and increased arterial stiffness in patients with cardiac syndrome X.

AIMS: Endothelial dysfunction and subangiographic atheroma have been reported in patients with cardiac syndrome X (CSX) but little is known regarding chronic inflammation and reduced arterial distensibility as pathogenic mechanisms. We assessed whether markers of inflammation and arterial distensibility differ in CSX patients compared to control subjects. METHODS AND RESULTS: We studied 30 consecutive CSX patients (mean age 57+/-6 years, 25 women) and 30 healthy controls (mean age 54+/-8 years, 25 women). High sensitivity C-reactive protein (hs-CRP) levels were significantly higher in patients with CSX compared to controls (2.6 [1.7-4.5] vs 1.5[0.7-2.7] mg/l, P=0.02). Hs-CRP levels correlated with carotid intima-media thickness (IMT) (Spearman's rho=0.51; P=0.013). CSX patients also had significantly increased mean IMT values than controls (P<0.0001). Arterial stiffness and elastic modulus were also significantly increased in CSX patients compared to control subjects (P=0.04 and P=0.04, respectively). Distensibility tended to be lower in CSX patients than controls although this difference did not reach statistical significance. CONCLUSIONS: This study showed for the first time that compared to control subjects, patients with CSX have higher hs-CRP serum levels, increased mean common carotid artery IMT and increased arterial stiffness. The role of these abnormalities in the pathogenesis of CSX deserves investigation.

Adult↗

Contribution of parasite proteins to altered mechanical properties of malaria-infected red blood cells.

Red blood cells (RBCs) parasitized by Plasmodium falciparum are rigid and poorly deformable and show abnormal circulatory behavior. During parasite development, knob-associated histidine-rich protein (KAHRP) and P falciparum erythrocyte membrane protein 3 (PfEMP3) are exported from the parasite and interact with the RBC membrane skeleton. Using micropipette aspiration, the membrane shear elastic modulus of RBCs infected with transgenic parasites (with kahrp or pfemp3 genes deleted) was measured to determine the contribution of these proteins to the increased rigidity of parasitized RBCs (PRBCs). In the absence of either protein, the level of membrane rigidification was significantly less than that caused by the normal parental parasite clone. KAHRP had a significantly greater effect on rigidification than PfEMP3, contributing approximately 51% of the overall increase that occurs in PRBCs compared to 15% for PfEMP3. This study provides the first quantitative information on the contribution of specific parasite proteins to altered mechanical properties of PRBCs.

Animals↗

Compounding of elastin polypentapeptide to collagen analogue: a potential elastomeric prosthetic material.

The polypentapeptide, H-(L . Val1-L . Pro2-Gly3-L . Val4-Gly5)n-L . Val-OMe, which is the most common recurring sequence within the elastic fiber, is demonstrated to be elastomeric when irradiation cross-linked but to have limited strength. On irradiation compounding with a collagen analogue, such as Dacron, stress-strain studies show the product to have an elastic modulus greater than that of fibrous aortic elastin and similar to that of aortic wall. In addition, the compounded product has the requisite strength. Of the 40, 50 and 60 MRAD cross-linked polypentapeptide-Dacron products, those derived from the larger doses of 50 and 60 MRAD exhibited somewhat better elastomeric properties. The unstretched and stretched products were characterized by scanning electron microscopy which demonstrated the importance of a fabric weave with a uniform extension. In general irradiation cross-linking has the advantage of being able to produce larger quantities of elastomeric material and compounding to a collagen analogue provides the required strength.

Collagen↗

Impedance planimetric characterization of the distal oesophagus in the Goettingen minipig.

Regional differences in biomechanical properties of the oesophagus were studied in 15 healthy Goettingen minipigs by means of impedance planimetry. The investigation was performed during anaesthesia by stepwise pressure-induced balloon distensions with concomitant measurement of pressure and luminal cross-sectional area (CSA) in the oesophagus 5 and 10 cm above the gastro-oesophageal junction. The circumferential wall tension, circumferential strain and incremental elastic modulus were computed from the measurements of pressure and CSA at steady-state conditions. Probably due to the anaesthesia, only scant peristalsis was recorded and the CSA always reached steady state during the balloon distensions. The CSAs were highest in the distal oesophagus (P < 0.001). At the highest induced pressure, the CSAs were 605 +/- 32 and 453 +/- 29 mm2 (mean +/- SEM) for the locations 5 and 10 cm from the gastro-oesophageal junction. The tension-strain distributions were non-linear and the curve obtained 5 cm above the gastro-oesophageal junction was shifted to the right when compared with the curve obtained from 10 cm above this junction. Fitting of the function tension = exp(a+b strain) to the data gave determination coefficients higher than 0.97 and P values lower than 0.001 for both measuring points. The constant a differed between the two locations in the oesophagus (P < 0.05). In conclusion, the pressure-CSA and the tension-strain distributions differed between the two measuring points suggesting that the elastic properties are different.

Anesthesia, General↗

In vitro evaluation of the viscoelastic properties of chitosan-thioglycolic acid conjugates.

The aim of this study was to evaluate the viscoelastic properties of chitosan-thioglycolic acid conjugates with different amounts of thiol groups immobilized on the polymer. The modification of chitosan was achieved via the covalent attachment of thioglycolic acid mediated by a carbodiimide. Chitosan-thioglycolic acid conjugates displaying 120, 209 and 439 microM thiol groups per gram of polymer were synthesized. The rheological properties of the three different conjugates were investigated. The elastic properties of the gels were found to increase significantly at pH 5.5. After 6 h the elastic modulus G' of chitosan-TGA 120, chitosan-TGA 209 and chitosan-TGA 439 gels increased 7-, 32- and 168-fold, respectively. In parallel the formation of disulfide bonds was observed. Accordingly, proof of principle that chitosan modified by the introduction of thiol groups has in situ gelling properties due to the formation of inter- and intramolecular disulfide bonds at physiological pH values is provided. Based on their in situ gelling properties, chitosan-thioglycolic acid conjugates seem to be very promising new excipients for liquid or semisolid formulations which should stabilize themselves once applied on the site of drug delivery.

Chitin↗

The stiffening of arteries by the tissue-mimicking gelatin.

Pulse wave velocity (PWV) is widely used for estimating the stiffness of an artery. PWV is measured by the time of travel of the "foot" of the pressure wave over a known distance. This technique has a low time resolution and is an average measurement of artery stiffness between the two measuring sites. The elastic modulus of the artery can be estimated with PWV, but the surrounding tissue effects are not considered. In this paper an external short pulse wave is generated noninvasively in the arterial wall by the radiation force of ultrasound. The pulse wave velocity in the artery is measured by a scanning technique with high-time resolution. The effect of tissue-mimicking gelatin on the artery is analyzed by measuring the wave velocity of the artery without and embedded in gelatin. It is found that the tissue-mimicking gelatin significantly stiffens the rubber tube and the artery if they are embedded in gelatin.

Animals↗

Ex vivo biomechanical properties of the female urethra in a rat model of birth trauma.

Stress urinary incontinence (SUI) is the involuntary release of urine during sudden increases in abdominal pressures. SUI is common in women after vaginal delivery or pelvic trauma and may alter the biomechanical properties of the urethra. Thus we hypothesize that injury due to vaginal distension (VD) decreases urethral basal tone and passive stiffness. This study aimed to assess the biomechanical properties of the urethra after VD in the baseline state, where basal muscle tone and extracellular matrix (ECM) are present, and in the passive state, where inactive muscle and ECM are present. Female rat urethras were isolated in a rat model of acute SUI induced by simulated birth trauma. Our established ex vivo system was utilized, wherein we applied intraluminal static pressures ranging from 0 to 20 mmHg. Outer diameter was measured via a laser micrometer. Measurements were recorded via computer. Urethral thickness was assessed histologically. Stress-strain responses of the urethra were altered by VD. Quantification of biomechanical parameters indicated that VD decreased baseline stiffness. The passive peak incremental elastic modulus of the distal segment in VD urethras was less than for controls (1.84 +/- 0.67 vs. 1.19 +/- 0.70 x 10(6) dyne/cm(2), respectively; P = 0.016). An increase was noted in passive low-pressure compliance values in proximal VD urethras compared with controls (9.44 +/- 2.43 vs. 4.62 +/- 0.60 mmHg(-1), respectively; P = 0.04). Biomechanical analyses suggest that VD alters urethral basal tone, proximal urethral compliance, and distal stiffness. Lack of basal smooth muscle tone, in combination with these changes in the proximal and distal urethra, may contribute to SUI induced by VD.

Animals↗

Poroelastography: imaging the poroelastic properties of tissues.

In the field of elastography, biological tissues are conveniently assumed to be purely elastic solids. However, several tissues, including brain, cartilage and edematous soft tissues, have long been known to be poroelastic. The objective of this study is to show the feasibility of imaging the poroelastic properties of tissue-like materials. A poroelastic material is a material saturated with fluid that flows relative to a deforming solid matrix. In this paper, we describe a method for estimating the poroelastic attributes of tissues. It has been analytically shown that during stress relaxation of a poroelastic material (i.e., sustained application of a constant applied strain over time), the lateral-to-axial strain ratio decreases exponentially with time toward the Poisson's ratio of the solid matrix. The time constant of this variation depends on the elastic modulus of the solid matrix, its permeability and its dimension along the direction of fluid flow. Recently, we described an elastographic method that can be used to map axial and lateral tissue strains. In this study, we use the same method in a stress relaxation case to measure the time-dependent lateral-to-axial strain ratio in poroelastic materials. The resulting time-sequenced images (poroelastograms) depict the spatial distribution of the fluid within the solid at each time instant, and help to differentiate poroelastic materials of distinct Poisson's ratios and permeabilities of the solid matrix. Results are shown from finite-element simulations.

Elasticity↗

Acrylic bone cements modified with beta-TCP particles encapsulated with poly(ethylene glycol).

Beta-tricalcium phosphate (beta-TCP) has been encapsulated with poly(ethylene glycol) (PEG) to improve the filler/cement interface, and it was later incorporated to a poly(methyl methacrylate) bone cement in order to obtain cements with improved stability in the long term. Size and size distribution of the agglomerates forming the initial powder was drastically changed after its dispersion in a PEG aqueous solution. Whereas the initial beta-TCP particles had a 584 microm average diameter, the treated particles (TCP-PEG) presented more than 60% of the particles in a range of 2-6 microm. The effect of adding the treated particles to an acrylic cement was evaluated in terms of curing parameters, in vitro behaviour and mechanical performance. The presence of the TCP-PEG particles did not affect either peak temperature or setting time, indicating a good homogeneity of polymerising mass in contrast to the effect observed with the plain beta-TCP particles, which gave rise to higher setting times. In vitro behaviour studies revealed hydration degree values of the modified cements comparable to that of PMMA cements. Early stages of water uptake was Fickian in nature for all the experimental formulations indicating that the water absorption followed a diffusion controlled mechanism. After 3 months of storage in SBF the experimental formulations presented values of compressive strength in the range 76-78 MPa, higher than the minimum required by ISO 5833 (70 MPa) and those of tensile strength in the range 42-48 MPa, higher than the minimum reported for commercial formulations (30 MPa), but no significant differences in the strengths and elastic modulus were observed with the treatment of the filler particles. This observation was confirmed by ESEM analysis of the tensile fracture surfaces, which revealed a rather good cohesion between the bioceramic particles with some gaps around them, independently of the type of particles. The themogravimetric analysis of dry and wet specimens showed a higher dissolution rate of the plain beta-TCP particles in comparison to the encapsulated ones, indicating that the PEG adsorbed on the surface of the TCP particles could be a way to control the resorbability of the bioceramic component.

Absorption↗

Biphasic surface amorphous layer lubrication of articular cartilage.

The biphasic nature of articular cartilage has been acknowledged for some time and is known to play an important role in many of the biomechanical functions performed by this unique tissue. From the lubrication point of view however, a simple biphasic model is unable to account for the extremely low friction coefficients that have been recorded experimentally, particularly during start-up. In addition, research over the last decade has indicated the presence of a surface amorphous layer on top of articular cartilage. Here, we present results from a finite element model of articular cartilage that includes a thin, soft, biphasic surface amorphous layer (BSAL). The results of this study show that a thin BSAL, with lower elastic modulus, dramatically altered the load sharing between the solid and liquid phases of articular cartilage, particularly in the near-surface regions of the underlying bulk cartilage and within the surface amorphous layer itself where the fluid load support exceeded 85%. By transferring the load from the solid phase to the fluid phase, the biphasic surface layer improves lubrication and reduces friction, whilst also protecting the underlying cartilage surface by 'shielding' the solid phase from elevated stresses. The increase in lubrication effectiveness is shown to be greatest during short duration loading scenarios, such as shock loads.

Biomechanical Phenomena↗

Surface chemical and mechanical properties of plasma-polymerized N-isopropylacrylamide.

Surface-immobilized poly(N-isopropyl acrylamide) (pNIPAM) is currently used for a wide variety of biosensor and biomaterial applications. A thorough characterization of the surface properties of pNIPAM thin films will benefit those applications. In this work, we present analysis of a plasma-polymerized NIPAM (ppNIPAM) coating by multiple surface analytical techniques, including time-of-flight secondary-ion mass spectrometry (ToF-SIMS), contact angle measurement, atomic force microscopy (AFM), and sum frequency generation (SFG) vibrational spectroscopy. ToF-SIMS data show that the plasma-deposited NIPAM polymer on the substrate is cross-linked with a good retention of the monomer integrity. Contact angle results confirm the thermoresponsive nature of the film as observed by a change of surface wettability as a function of temperature. Topographic and force-distance curve measurements by AFM further demonstrate that the grafted film shrinks or swells depending on the temperature of the aqueous environment. A clear transition of the elastic modulus is observed at 31-32 degrees C. The change of the surface wettability and mechanical properties vs temperature are attributed to different conformations taken by the polymer, which is reflected on the outmost surface as distinct side chain groups orienting outward at different temperatures as measured by SFG. The results suggest that a ppNIPAM thin film on a substrate experiences similar mechanical and chemical changes to pNIPAM bulk polymers in solution. The SFG result provides evidence supporting the current theory of the lower critical solution temperature (LCST) behavior of pNIPAM.

Acrylic Resins↗

A validated finite element method study of orthodontic tooth movement in the human subject.

The aim of the study was to develop a 3D computer model of the movement of a maxillary incisor tooth when subjected to an orthodontic load. A novel method was to be developed to directly and accurately measure orthodontic tooth movement in a group of human volunteers. This was to be used to validate the finite element-based computer model. The design took the form of a prospective experiment at a laboratory at the University of Wales in 1996/7. A laser apparatus was used to sample tooth movement every 0.01 seconds over a 1-minute cycle for 10 healthy volunteers, whilst a constant 0.39 N load was applied. This process was repeated on eight separate occasions and the most consistent five readings taken for each subject. Data were used to calculate the physical properties of the periodontal ligament (PDL). The data gleaned by this method were used to validate the 3D FEM model. This was formed of 15,000 four-noded tetrahedral elements. Tooth displacements ranged from 0.012 to 0.133 mm. An appropriate elastic modulus of 1 N/mm(2) and Poisson's Ratio of 0.45 was derived for the PDL. Strain analysis, using the model, suggested that a maximum PDL strain of 4.77 x 10(-3) was recorded at the alveolar crest, while the largest apical strain recorded was 1.55 x 10(-3). The maximum strains recorded in the surrounding alveolar bone were 35 times less than for the PDL. A novel method for direct measurement of PDL physical properties in the human subject has been developed. The validated FEM model lends further evidence that the PDL is the main mediator of orthodontic tooth movement.

Adult↗

Applications of digital image correlation to biological tissues.

Optical methods are becoming commonplace in investigations of the physical and mechanical behavior of biological tissues. Digital image correlation (DIC) is a versatile optical method that shows tremendous promise for applications involving biological tissues and biomaterials. We present the fundamentals of DIC with an emphasis on the application to biological materials. An approach for surface preparation is described that facilitates its application to hydrated substrates. Three examples are presented that highlight the use of DIC for biomedical research. The first example describes the use of DIC to study the mechanical behavior of arterial tissues up to 40% elongation. The second example describes an evaluation of the mechanical properties of bovine hoof horn in the dehydrated and fully hydrated states. Uniaxial tension experiments are performed to determine the elastic modulus (E) and Poisson's ratio (nu) of both the arterial and dermal tissues. Spatial variations in the mechanical properties are evident from the full-field characterization of both tissues. Finally, an application of DIC to study the evolution of loosening in cemented total hip replacements is described. The noncontact analysis enables measurement of the relative displacement between the bone/bone cement and bone cement/prosthesis interfaces. Based on the elementary optical arrangement, the simple surface preparation, and the ability to acquire displacement/strain measurements over a large range of deformation, DIC should serve as a valuable tool for biomedical research. Further developments will enable the use of DIC for in vivo applications.

Algorithms↗

The gelation kinetics of platelet extracts.

The kinetics of the gelation process that occurs upon warming cold platelet extracts were studied using a sensitive rheometer. At micromolar or less free Ca2+ concentrations and in the presence of 1 mM ATP, the gel rigidity curves showed several peaks, indicating that platelet extract proteins went through network assembling/disassembling cycles during gelation. The gelation kinetics were accelerated by increasing the free Ca2+ concentration up to about 2 microM. At 4-15 microM free Ca2+, the gelation cycles were completely abolished except for the first peak. The gelation process became one of monotonically increasing elastic modulus at millimolar free Ca2+ concentrations. Trifluoperazine (50 microM), a calmodulin inhibitor, did not affect gelation at micromolar free Ca2+ concentrations. Except for the first gelation step, which was completed within 5 min after warming, the rest of the gelation process was found to be affected by K+, ATP, cytochalasin E and colchicine. K+ at concentrations higher than 10 mM retarded the gelation kinetics. Extracts prepared with low (0.1 mM) ATP content showed impaired gelation, and this was partially reversed by adding 1 mM ATP, but not 1 mM adenylylimidodiphosphate (p[NH]ppA). Both cytochalasin E (1 microM) and colchicine (1 mM) interfered with the gelation process.

Adenosine Triphosphate↗

Carotid artery plaque burden, stiffness, and mortality risk in elderly men: a prospective, population-based cohort study.

BACKGROUND: Indicators of carotid atherosclerosis may confer additional prognostic value and guide clinicians in cardiovascular risk assessment. Carotid artery morphology (plaque burden) and function (stiffness indexes) as predictors of all-cause and cardiovascular mortality were prospectively evaluated in elderly men. METHODS AND RESULTS: Cardiovascular risk profile was measured in 367 independently living men (mean+/- SD age, 78+/-4 years). The number of carotid plaques was assessed by B-mode ultrasound, and arterial stiffness was quantified with a wall tracker system. During 48 months of follow-up, 70 deaths (28 cardiovascular) occurred. The total number of carotid plaques was the parameter most closely related to prognosis. In the age-adjusted multivariate Cox model, all-cause mortality was predicted by number of plaques (hazard ratio [HR] per 1-unit increase, 1.35; 95% confidence interval [CI], 1.12 to 1.64). Predictors of cardiovascular mortality in the respective model were number of plaques (HR, 1.18; 95% CI, 1.04 to 1.33) and Young's elastic modulus (HR, 1.68; 95% CI, 1.26 to 2.26). Number of plaques improved the prognostic utility in any prognosis model when added to commonly available cardiovascular risk information. In contrast, stiffness indexes offered no consistent additive value. CONCLUSIONS: In elderly men, carotid artery plaque burden is a strong independent predictor of all-cause and cardiovascular mortality in the years to come. The additional value of carotid artery stiffness measurements as a pathophysiologically related entity appears to be limited in this age group and, if anything, confined to cardiovascular mortality risk.

Aged↗

Tangent simple systems method applied to a precise study of viscoelastic behaviour of human blood.

The tangent simple systems (TSS) method, proposed in (1), is applied in order to study the viscoelastic behaviour of human blood in transient flow for a rectangular low shear rate step. The tangent simple systems which were used are Maxwell liquids. These systems allow one to obtain plots of variations of instantaneous values of viscosity coefficient mu, elasticity modulus G and retardation time tau = mu/G of the studied blood samples, as a function of flow duration. Variations of both parameters mu and G versus time are represented by two exponential functions which involve three couples of parameters (mu o, mu infinity), (Go, G infinity) and (tau mu, tau G). These parameters can be considered as the characteristics of each blood sample. Another representation of the results, called the dual rheogram, is also indicated. The dual rheogram enables one to follow the evolution of the blood structure. Several examples of application of the TSS method to normal blood sample and to suspensions of artificially modified red blood cells (RBC) are given.

Blood Viscosity↗