Transient receptor potential vanilloid-4 contributes to stretch-induced hypercontractility and time-dependent dysfunction in the aged heart

Aims Cardiovascular disease remains the greatest cause of mortality in Americans over 65. The stretch-activated transient receptor potential vanilloid-4 (TRPV4) ion channel is expressed in cardiomyocytes of the aged heart. This investigation tests the hypothesis that TRPV4 alters Ca2+ handling and cardiac function in response to increased ventricular preload and cardiomyocyte stretch. Methods and results Left ventricular maximal pressure (PMax) was monitored in isolated working hearts of Aged (24–27 months) mice following preload elevation from 5 to 20mmHg, with and without TRPV4 antagonist HC067047 (HC, 1 µmol/L). In preload responsive hearts, PMax prior to and immediately following preload elevation (i.e. Frank–Starling response) was similar between Aged and Aged+HC. Within 1 min following preload elevation, Aged hearts demonstrated secondary PMax augmentation (Aged>Aged+HC) suggesting a role for stretch-activated TRPV4 in cardiac hypercontractility. However, after 20 min at 20 mmHg Aged exhibited depressed PMax (Aged<Aged+HC) suggestive of TRPV4-dependent contractile dysfunction with sustained stretch. To examine stretch-induced Ca2+ homeostasis at the single-cell level, isolated cardiomyocytes were stretched 10–15% of slack length while measuring intracellular Ca2+ with fura-2. Uniaxial longitudinal stretch increased intracellular Ca2+ levels and triggered Ca2+ overload and terminal cellular contracture in Aged, but not Aged+HC. Preload elevation in hearts of young/middle-age (3–12 months) mice produced an initial PMax increase (Frank–Starling response) without secondary PMax augmentation, and cardiomyocyte stretch did not affect intracellular Ca2+ levels. Hearts of transgenic mice with cardiac-specific TRPV4 expression exhibited PMax similar to 3- to 12-month control mice prior to and immediately following preload elevation but displayed secondary PMax augmentation. Cardiomyocytes of mice with transgenic TRPV4 expression were highly sensitive to mechanical stimulation and exhibited elevated Ca2+ levels, Ca2+ overload, and terminal contracture upon cellular attachment and stretch. Conclusion TRPV4 contributes to a stretch-induced increase in cardiomyocyte Ca2+ and cardiac hypercontractility, yet sustained stretch leads to cardiomyocyte Ca2+ overload and contractile dysfunction in the aged heart.

Multi-Scale Study of Tensile Mechanical Properties of Carbon Nanotube Film under Lateral Loading

In this paper, tensile mechanical properties of carbon nanotube (CNT) film under lateral loading are measured. Comparing with works before, it is found that elastic modulus of CNT film under lateral stretch is higher than that under longitudinal stretch, which is an interesting experimental result. With multi-scale experimental methods including SEM and micro-Raman spectroscopy, the change of CNT bundle network of the film under lateral stretch and axial elongation of CNTs in the loading direction are measured. Based on the experimental results, the control mechanism on difference of lateral and longitudinal mechanical properties of CNT film is analyzed.

Tuning Elastic Waves in Soft Phononic Crystal Cylinders Via Large Deformation and Electromechanical Coupling

Soft electroactive materials can undergo large deformation subjected to either mechanical or electrical stimulus, and hence, they can be excellent candidates for designing extremely flexible and adaptive structures and devices. This paper proposes a simple one-dimensional soft phononic crystal (PC) cylinder made of dielectric elastomer (DE) to show how large deformation and electric field can be used jointly to tune the longitudinal waves propagating in the PC. A series of soft electrodes, which are mechanically negligible, are placed periodically along the DE cylinder, and hence, the material can be regarded as uniform in the undeformed state. This is also the case for the uniformly prestretched state induced by a static axial force only. The effective periodicity of the structure is then achieved through two loading paths, i.e., by maintaining the longitudinal stretch and applying an electric voltage over any two neighboring electrodes or by holding the axial force and applying the voltage. All physical field variables for both configurations can be determined exactly based on the nonlinear theory of electroelasticity. An infinitesimal wave motion is further superimposed on the predeformed configurations, and the corresponding dispersion equations are derived analytically by invoking the linearized theory for incremental motions. Numerical examples are finally considered to show the tunability of wave propagation behavior in the soft PC cylinder. The outstanding performance regarding the band gap (BG) property of the proposed soft dielectric PC is clearly demonstrated by comparing with the conventional design adopting the hard piezoelectric material. One particular point that should be emphasized is that soft dielectric PCs are susceptible to various kinds of failure (buckling, electromechanical instability (EMI), electric breakdown (EB), etc.), imposing corresponding limits on the external stimuli. This has been carefully examined for the present soft PC cylinder such that the applied electric voltage is always assumed to be less than the critical voltage except for one case, in which we illustrate that the snap-through instability of the axially free PC cylinder made of a generalized Gent material may be used to efficiently trigger a sharp transition in the BGs.

Repeated Loading Behavior of Pediatric Porcine Common Carotid Arteries

Rapid flexion and extension of the neck may occur during scenarios associated with traumatic brain injury (TBI), and understanding the mechanical response of the common carotid artery (CCA) to longitudinal stretch may enhance understanding of contributing factors that may influence CCA vasospasm and exacerbate ischemic injury associated with TBI. Immature (4-week-old) porcine CCAs were tested under subcatastrophic (1.5 peak stretch ratio) cyclic loading at 3 Hz for 30 s. Under subcatastrophic cyclic longitudinal extension, the immature porcine CCA displays softening behavior. This softening can be represented by decreasing peak stress and increasing corner stretch values with an increasing number of loading cycles. This investigation is an important first step in the exploration of fatiguelike behavior in arterial tissue that may be subjected to repeated longitudinal loads.

Impact of the Low Head Dam/Barrage on Fisheries – A Case Study of Giri River of Yamuna Basin (India)

Shannon’s diversity index H’ = pi log2 pi was calculated for 16 fish species. The index was resolved into its components, species richness and relative abundance, to determine which components played a larger role in the determination of diversity pattern. Changes in diversity were correlated with species richness (r), habitat heterogeneity, and hydrological regimes in a longitudinal stretch of 35 km along the river Giri, a major tributary of the Yamuna River system, in Western Himalayas. Abundance differs with change in habitat structures, habitat preference of fish species and water regimes. The decrease in diversity in the lower stretch of about 3-4 km upstream of the barrage was found to be associated with habitat fragmentation and as well as d/s with loss of biotic integrity of aquatic ecosystem due to water scarcity. Species richness was found to be maximum at upper and middle reaches (elevation 650-800 m, msl) of the river, whereas it was low in lower reaches. Change in water chemistry was also noticed at Jatan barrage-low head dam due to impoundment of river water. It is inferred that the regulation of water has an impact on species richness and relative abundance, and on habitat heterogeneity which has decreased due to the change in environmental condition.

Antiplane wave scattering from a cylindrical cavity in pre-stressed nonlinear elastic media

The effect of a longitudinal stretch and a pressure-induced inhomogeneous radial deformation on the scattering of antiplane elastic waves from a cylindrical cavity is determined. Three popular nonlinear strain energy functions are considered: the neo-Hookean, the Mooney–Rivlin and a two-term Arruda–Boyce model. A new method is developed to analyse and solve the governing wave equations. It exploits their properties to determine an asymptotic solution in the far-field, which is then used to derive a boundary condition to numerically evaluate the equations local to the cavity. This method could be applied to any linear ordinary differential equation whose inhomogeneous coefficients tend to a constant as its independent variable tends to infinity. The effect of the pre-stress is evaluated by considering the scattering cross section. A longitudinal stretch is found to decrease the scattered power emanating from the cavity, whereas a compression increases it. The effect of the pressure difference depends on the strain energy function employed. For a Mooney–Rivlin material, a cavity inflation increases the scattered power and a deflation decreases it; for a neo-Hookean material, the scattering cross section is unaffected by the radial deformation; and for a two-term Arruda–Boyce material, both inflation and deflation are found to decrease the scattered power.

In-Plane Nonlinear Buckling of Funicular Arches

This paper presents a numerical technique to determine the full pre-buckling and post-buckling equilibrium path for elastic funicular arches. The formulation includes the effects of shear deformations and geometric nonlinearity due to large deformations. The Timoshenko beam hypothesis is adopted for incorporating shear. Finite strains are considered without approximation. The finite strains are defined in terms of the normal and shear component of the longitudinal stretch. The constitutive relations for the internal actions are based on a hyperelastic constitutive model. Using the differential equilibrium equations and the constitutive laws, the nonlinear buckling behavior of some typical funicular arches are investigated using the trapezoid method with Richardson extrapolation enhancement. The results are validated by using the finite element package ANSYS and solutions available in the literature. Examples include parabolic arches under a uniformly distributed gravity load, a catenary under a distributed load along the arch and a catenary arch under an overburden load. Parametric studies are performed to identify the factors that influence the nonlinear buckling of funicular arches. The axial to shear rigidity ratio is shown to have a significant effect on the buckling load and the buckling mode shape.

Longitudinal distribution of Chironomidae (Diptera) downstream from a dam in a neotropical river

The damming of a river causes dangerous consequences on structure of the environment downstream of the dam, modifying the sediment composition, which impose major adjustments in longitudinal distribution of benthic community. The construction of Engenheiro Sérgio Motta Dam in the Upper Paraná River has caused impacts on the aquatic communities, which are not yet fully known. This work aimed to provide more information about the effects of this impoundment on the structure of Chironomidae larvae assemblage. The analysis of data of physical and chemical variables in relation to biological data of 8 longitudinal sections in the Upper Paraná River showed that composition of Chironomidae larvae of stations near Engenheiro Sérgio Motta Dam differed of the other stations (farther of the Dam). The predominance of coarse sediments at stations upstream and finer sediments further downstream affected the choice of habitat by different morphotypes of Chironomidae and it caused a change in the structure of this assemblage in the longitudinal stretch.

Bladder smooth muscle organ culture preparation maintains the contractile phenotype

Smooth muscle cells, when subjected to culture, modulate from a contractile to a secretory phenotype. This has hampered the use of cell culture for molecular techniques to study the regulation of smooth muscle biology. The goal of this study was to develop a new organ culture model of bladder smooth muscle (BSM) that would maintain the contractile phenotype and aid in the study of BSM biology. Our results showed that strips of BSM subjected to up to 9 days of organ culture maintained their contractile phenotype, including the ability to achieve near-control levels of force with a temporal profile similar to that of noncultured tissues. The technical aspects of our organ culture preparation that were responsible, in part, for the maintenance of the contractile phenotype were a slight longitudinal stretch during culture and subjection of the strips to daily contraction-relaxation. The tissues contained viable cells throughout the cross section of the strips. There was an increase in extracellular collagenous matrix, resulting in a leftward shift in the passive length-tension relationship. There were no significant changes in the content of smooth muscle-specific α-actin, calponin, h-caldesmon, total myosin heavy chain, protein kinase G, Rho kinase-I, or the ratio of SM1 to SM2 myosin isoforms. Moreover the organ cultured tissues maintained functional voltage-gated calcium channels and large-conductance calcium-activated potassium channels. Therefore, we propose that this novel BSM organ culture model maintains the contractile phenotype and will be a valuable tool for the use in cellular/molecular biology studies of bladder myocytes.