Xiao Lu

Regional distribution of axial strain and circumferential residual strain in the layered rabbit oesophagus

The oesophagus is subjected to large axial strains in vivo and the zero-stress state is not a closed cylinder but an open circular cylindrical sector. The closed cylinder with no external loads applied is called the no-load state and residual strain is the difference in strain between the no-load state and zero-stress state. To understand oesophageal physiology and pathophysiology, it is necessary to know the distribution of axial strain, the zero-stress state, the stress-strain relations of oesophageal tissue, and the changes of these states and relationships due to biological remodeling of the tissue under stress. This study is addressed to such biomechanical properties in normal rabbits. The oesophagi were marked on the surface in vivo, photographed, excised (in vitro state), photographed again, and sectioned into rings (no-load state) in an organ bath containing calcium-free Krebs solution with dextran and EGTA added. The rings were cut radially to obtain the zero-stress state for the non-separated wall and further dissected to separate the muscle and submucosa layers. Equilibrium was awaited for 30min in each state and the specimens were photographed in no-load and the zero-stress states. The oesophageal length, circumferences, layer thicknesses and areas, and openings angle were measured from the digitised images. The oesophagus shortened axially by 35% after excision. The in vivo axial strain showed a significant variation with the highest values in the mid-oesophagus (p<0.001). Luminal area, circumferences, and wall and layer thicknesses and areas varied in axial direction (in all tests p<0.05). The residual strain was compressive at the mucosal surface and tensile at the serosal surface. The dissection studies demonstrated shear forces between the two layers in the non-separated wall in the no-load and zero-stress states. In conclusion, our data show significant axial variation in passive morphometric and biomechanical properties of the oesophagus. The oesophagus is a layered composite structure with nonlinear and anisotropic mechanical behaviour.

NADPH oxidase has a directional response to shear stress

Vessel regions with predilection to atherosclerosis have negative wall shear stress due to flow reversal. The flow reversal causes the production of superoxides (O(2)(-)), which scavenge nitric oxide (NO), leading to a decrease in NO bioavailability and endothelial dysfunction. Here, we implicate NADPH oxidase as the primary source of O(2)(-) during full flow reversal. Nitrite production and the degree of vasodilation were measured in 46 porcine common femoral arteries in an ex vivo system. Nitrite production and vasodilation were determined before and after the inhibition of NADPH oxidase, xanthine oxidase, or mitochondrial oxidase. NADPH oxidase inhibition with gp91ds-tat or apocynin restored nitrite production and vasodilation during reverse flow. Xanthine oxidase inhibition increased nitrite production at the highest flow rate, whereas mitochondrial oxidase inhibition had no effect. These findings suggest that the NADPH oxidase system can respond to directional changes of flow and is activated to generate O(2)(-) during reverse flow in a dose-dependent fashion. These findings have important clinical implications for oxidative balance and NO bioavailability in regions of flow reversal in a normal and compromised cardiovascular system.

Experimentally Validated Microstructural 3D Constitutive Model of Coronary Arterial Media

Accurate modeling of arterial response to physiological or pathological loads may shed light on the processes leading to initiation and progression of a number of vascular diseases and may serve as a tool for prediction and diagnosis. In this study, a microstructure based hyperelastic constitutive model is developed for passive media of porcine coronary arteries. The most general model contains 12 independent parameters representing the three-dimensional inner fibrous structure of the media and includes the effects of residual stresses and osmotic swelling. Parameter estimation and model validation were based on mechanical data of porcine left anterior descending (LAD) media under radial inflation, axial extension, and twist tests. The results show that a reduced four parameter model is sufficient to reliably predict the passive mechanical properties. These parameters represent the stiffness and the helical orientation of each lamellae fiber and the stiffness of the interlamellar struts interconnecting these lamellae. Other structural features, such as orientational distribution of helical fibers and anisotropy of the interlamellar network, as well as possible transmural distribution of structural features, were found to have little effect on the global media mechanical response. It is shown that the model provides good predictions of the LAD media twist response based on parameters estimated from only biaxial tests of inflation and extension. In addition, good predictive capabilities are demonstrated for the model behavior at high axial stretch ratio based on data of law stretches.

Constitutive Modeling of Coronary Arterial Media - Comparison of Three Model Classes

Accurate modeling of arterial elasticity is imperative for predicting pulsatile blood flow and transport to the periphery, and for evaluating the mechanical microenvironment of the vessel wall. The goal of the present study is to compare a recently developed structural model of porcine left anterior descending artery media to two commonly used typical representatives of phenomenological and structure-motivated invariant-based models, in terms of the number of model parameters, model descriptive and predictive powers, and requisite different test protocols for reliable parameter estimation. The three models were compared against 3D data of radial inflation, axial extension, and twist tests. Also checked are the models predictive capabilities to response data not used for estimation, including both tests outside the range of estimation database, as well as protocols of a different nature. The results show that the descriptive estimation error (model fit to estimation database), measured by the sum of squared residuals (SSE) between full 3D data and model predictions, was about twice as low for the structural (4.58%) model compared to the other two (9.71 and 8.99% for the phenomenological and structure-motivated models, respectively). Similar SSE ratios were obtained for the predictive capabilities. Prediction SSE at high stretch based on estimation of two low stretches yielded an SSE value of 2.81% for the structural model, and 10.54% and 7.87% for the phenomenological and structure-motivated models, respectively. For the prediction of twist from inflation-extension data, SSE values for the torsional stiffness was 1.76% for the structural model and 39.62 and 2.77% for the phenomenological and structure-motivated models. The required number of model parameters for the structural model is four, whereas the phenomenological model requires six to nine and the structure-motivated has four parameters. These results suggest that modeling based on the tissue structural features improves model reliability in describing given data and in predicting the tissue general response.

Morphometric and biomechanical remodelling in the intestine after small bowel resection in the rat

The short‐bowel syndrome is a clinical condition caused by intestinal resection. As intestinal adaptation occurs after resection, it can be used as a model for studying morphometric and biomechanical remodelling in the small intestine and to get a better understanding of the pathophysiology of the short‐bowel syndrome. The resected rats had a 67% resection of jejunum and ileum. Control animals underwent no operation (nonoperated controls) or an ileal transection with subsequent end‐to‐end anastomosis (sham‐resected controls). The animals were followed for up to 4 weeks after the operation. Changes in biomechanical properties were studied in terms of residual strain (the internal strain remaining when all external loads are removed), opening angle and stress–strain relations referenced to the zero‐stress state (the cut‐open state where external and internal stresses are released). The resected animals gained less weight than the controls. The intestinal length and diameter increased more in the resected groups than the control groups (P < 0.05), resulting in a larger absorptive surface. Resection induced profound gross morphometric changes and histological alterations characterized by proliferative increases in the tissue layers. The opening angle, along with residual strain at the mucosal and serosal surface, increased in the remnant small intestine (P < 0.05). All changes increased as function of postoperative time and were most prominent in the remnant ileum. However, the stress–strain relationship remained unchanged. In conclusion, this study demonstrated that resection of the majority of the small bowel results in significant remodelling in structural and residual strain properties in the remnant small intestine. The remodelling seems to be guided by the need for a greater absorptive surface area rather than for a change in the stress–strain properties.

Biaxial vasoactivity of porcine coronary artery

The passive mechanical properties of blood vessel mainly stem from the interaction of collagen and elastin fibers, but vessel constriction is attributed to smooth muscle cell (SMC) contraction. Although the passive properties of coronary arteries have been well characterized, the active biaxial stress-strain relationship is not known. Here, we carry out biaxial (inflation and axial extension) mechanical tests in right coronary arteries that provide the active coronary stress-strain relationship in circumferential and axial directions. Based on the measurements, a biaxial active strain energy function is proposed to quantify the constitutive stress-strain relationship in the physiological range of loading. The strain energy is expressed as a Gauss error function in the physiological pressure range. In K(+)-induced vasoconstriction, the mean ± SE values of outer diameters at transmural pressure of 80 mmHg were 3.41 ± 0.17 and 3.28 ± 0.24 mm at axial stretch ratios of 1.3 and 1.5, respectively, which were significantly smaller than those in Ca(2+)-free-induced vasodilated state (i.e., 4.01 ± 0.16 and 3.75 ± 0.20 mm, respectively). The mean ± SE values of the inner and outer diameters in no-load state and the opening angles in zero-stress state were 1.69 ± 0.04 mm and 2.25 ± 0.08 mm and 126 ± 22°, respectively. The active stresses have a maximal value at the passive pressure of 80-100 mmHg and at the active pressure of 140-160 mmHg. Moreover, a mechanical analysis shows a significant reduction of mean stress and strain (averaged through the vessel wall). These findings have important implications for understanding SMC mechanics.

Assessment of endothelial function of large, medium, and small vessels: a unified myograph.

Endothelial dysfunction precedes the development of morphological atherosclerotic changes and can also contribute to lesion development in cardiovascular diseases. Currently, there is a lack of a single method to determine endothelial function of the entire range of vessel dimensions from aorta to arterioles. Here we assessed endothelial function of a large range of size arteries using a unified isovolumic myograph method. The method maintains a constant volume of fluid in the lumen of the vessel during contraction and relaxation, which are characterized by an increase and a decrease of pressure, respectively. Segments of six aortas, six common femoral arteries, and six mesenteric arteries from rats; six carotid arteries from mice; and six coronary and carotid arteries from pigs were used. The endothelium-dependent dose-response vasorelaxation was determined with endothelium-dependent vasodilators while arterial preconstriction was induced with vasoconstrictors at a submaximal dose. The circumferential midtension during vascular reactivity varied from 43.1 ± 7.9 to 2.59 ± 0.46 mN/mm (from large to small arteries), whereas the circumferential midstress showed a much smaller variation from 217 ± 23.5 to 123 ± 15.3 kPa (in the same range of vessels). We also found that overinflation and axial overelongation compromised endothelium-dependent vasorelaxation to underscore the significance of vessel preload. In conclusion, an isovolumic myograph was used to unify arterial vasoreactivity from large to small arteries and shows the uniformity of wall stress and %tension throughout the range of vessel sizes.

Biomechanical properties of porcine cerebral bridging veins with reference to the zero-stress state.

Passive mechanical and morphometric properties of porcine cerebral bridging veins were studied. Fifteen cerebral bridging veins were obtained from 7 pigs. The superior sagittal sinus, bridging veins and the meninges were excised and placed in aerated calcium-free Krebs solution. The outflow cuff segment is a narrow region at the junction of the cerebral bridging veins and superior sagittal sinus. The principal direction of collagen fibres was longitudinal in the bridging vein and circumferential in the cuff region. The diameter was smaller in the outflow cuff segment than in the cerebral bridging veins in the pressure range studied (0–23 mm Hg) whereas the thickness was highest in the outflow cuff segment (p < 0.01). The circumferential stress-strain analysis showed that the outflow cuff segment was extensible up to a strain of 0.25. At higher strains the outflow cuff segment was progressively stiffer than the cerebral bridging vein (p < 0.05). The longitudinal stress-strain relation for the cerebral bridging vein was shifted to the left compared to the outflow cuff segment (p < 0.05). When compared to the stress-strain properties in the circumferential direction, the outflow cuff segment was more extensible and the cerebral bridging vein stiffer in longitudinal direction (p < 0.05). The opening angle of the outflow cuff segment and the cerebral bridging vein was 115 ± 4 and 120 ± 4 (means ± SE) without statistical difference between the two regions. In conclusion the difference in biomechanical properties between the outflow cuff segment and the cerebral bridging vein was associated to their difference in histology and fibre arrangement. This indicates that the function of the outflow cuff segment is to act as a flow-limiting resistance to the outflow from the cerebral circulation.

Elevated oxidative stress and endothelial dysfunction in right coronary artery of right ventricular hypertrophy

Remodeling of right coronary artery (RCA) occurs during right ventricular hypertrophy (RVH) induced by banding of the pulmonary artery (PA). The effect of RVH on RCA endothelial function and reactive oxygen species (ROS) in vessel wall remains unclear. A swine RVH model (n = 12 pigs) induced by PA banding was used to study RCA endothelial function and ROS level. To obtain longitudinal coronary hemodynamic and geometric data, digital subtraction angiography was used during the progression of RVH. Blood flow in the RCA increased by 82% and lumen diameter of RCA increased by 22% over a 4-wk period of RVH. The increase in blood flow and the commensurate increase in diameter resulted in a constant wall shear stress in RCA throughout the RVH period. ROS was elevated by ∼100% in RCA after 4 wk of PA banding. The expressions of p47(phox), NADPH oxidase (NOX1, NOX2, and NOX4) were upregulated in the range of 20-300% in RCA of RVH. The endothelial function was compromised in RCA of RVH as attributed to insufficient endothelial nitric oxide synthase cofactor tetrahydrobiopterin. In vivo angiographic analysis suggests an increased basal tone in the RCA during RVH. In conclusion, stretch due to outward remodeling of RCA during RVH (at constant wall shear stress), similar to vessel stretch in hypertension, appears to induce ROS elevation, endothelial dysfunction, and an increase in basal tone.

Physiological growth is associated with esophageal morphometric and biomechanical changes in rats

Abstract  Esophageal geometry and biomechanical changes were studied during physiological growth in rats aged 1–32 weeks. Histological examination was done after the biomechanical study. The esophageal dimensions increased many‐fold from 1–32 weeks, e.g. the weight per unit length increased six‐fold and the wall cross‐sectional area increased eight‐fold. The inner and outer circumferential length of the mucosa and muscle, and the thickness and area of the layers increased as function of age. The opening angle was approximately 140 degrees at age 1 and 2 weeks and gradually decreased to approximately 80 degrees after 16 weeks. The circumferential and longitudinal stress–strain curves were exponential. The circumferential stress–strain curves shifted from left to the right up to 4 weeks of age (P < 0.001) where after no further change was observed, i.e. the esophagus became more compliant during the first 4 weeks of life. The longitudinal stress–strain curves shifted from left to the right up to 16 weeks of age (P < 0.001), i.e. the esophagus became more compliant longitudinally during the first 16 weeks of life. Bi‐axial stress–strain analysis with determination of mechanical tissue constants showed that the esophagus was stiffer in the longitudinal direction than in the circumferential direction. In conclusion, a pronounced morphometric and biomechanical remodelling was observed in the rat esophagus during physiological growth. The observed changes likely reflect the development of the physiological function of the esophagus since for other tissues the function dictates the form of the tissue, and growth and remodelling depend on the mechanical loading.