MRI-based finite-element analysis of left ventricular aneurysm

Tagged MRI and finite-element (FE) analysis are valuable tools in analyzing cardiac mechanics. To determine systolic material parameters in three-dimensional stress-strain relationships, we used tagged MRI to validate FE models of left ventricular (LV) aneurysm. Five sheep underwent anteroapical myocardial infarction (25% of LV mass) and 22 wk later underwent tagged MRI. Asymmetric FE models of the LV were formed to in vivo geometry from MRI and included aneurysm material properties measured with biaxial stretching, LV pressure measurements, and myofiber helix angles measured with diffusion tensor MRI. Systolic material parameters were determined that enabled FE models to reproduce midwall, systolic myocardial strains from tagged MRI (630 +/- 187 strain comparisons/animal). When contractile stress equal to 40% of the myofiber stress was added transverse to the muscle fiber, myocardial strain agreement improved by 27% between FE model predictions and experimental measurements (RMS error decreased from 0.074 +/- 0.016 to 0.054 +/- 0.011, P < 0.05). In infarct border zone (BZ), end-systolic midwall stress was elevated in both fiber (24.2 +/- 2.7 to 29.9 +/- 2.4 kPa, P < 0.01) and cross-fiber (5.5 +/- 0.7 to 11.7 +/- 1.3 kPa, P = 0.02) directions relative to noninfarct regions. Contrary to previous hypotheses but consistent with biaxial stretching experiments, active cross-fiber stress development is an integral part of LV systole; FE analysis with only uniaxial contracting stress is insufficient. Stress calculations from these validated models show 24% increase in fiber stress and 115% increase in cross-fiber stress at the BZ relative to remote regions, which may contribute to LV remodeling.     

Direct measurement of shear strain in adherent vascular endothelial cells exposed to fluid shear stress

Functional and morphological responses of endothelial cells (ECs) to fluid shear stress are thought to be mediated by several mechanosensitive molecules. However, how the force due to fluid shear stress applied to the apical surface of ECs is transmitted to the mechanosensors is poorly understood. In the present paper, we performed an analysis of an intracellular mechanical field by observation of the deformation behaviors of living ECs exposed to shear stress with a novel experimental method. Lateral images of human umbilical vein ECs before and after the onset of flow were obtained by confocal microscopy, and image correlation and finite element analysis were performed for quantitative analyses of subcellular strain due to shear stress. The shear strain of the cells changed from 1.06 ± 1.09% (mean ± SD) to 4.67 ± 1.79% as the magnitude of the shear stress increased from 2 to 10 Pa. The nuclei of ECs also exhibited shear deformation, which was similar to that observed in cytoplasm, suggesting that nuclei transmit forces from apical to intracellular components, as well as cytoskeletons. The obtained strain-stress relation resulted in a mean shear modulus of 213 Pa for adherent ECs. These results provide a mechanical perspective on the investigation of flow-sensing mechanisms of ECs.     

Magnitude of sarcomere extension correlates with initial sarcomere length during lengthening of activated single fibers from soleus muscle of rats

A laser-diffraction technique was developed that rapidly reports the lengths of sarcomeres (L_s) in serially connected sectors of permeabilized single fibers. The apparatus translates a laser beam along the entire length of a fiber segment within 2 ms, with brief stops at each of 20 contiguous sectors. We tested the hypothesis that during lengthening contractions, when maximally activated fibers are stretched, sectors that contain the longer sarcomeres undergo greater increases in L_s than those containing shorter sarcomeres. Fibers (n = 16) were obtained from the soleus muscles of adult male rats and the middle portions (length = 1.05 ± 0.11 mm; mean ± SD) were investigated. Single stretches of strain 27% and a strain rate of 54% s⁻¹ were initiated at maximum isometric stress and resulted in a 19 ± 9% loss in isometric stress. The data on L_s revealed that 1), the stretch was not distributed uniformly among the sectors, and 2), during the stretch, sectors at long L_s before the stretch elongated more than those at short lengths. The findings support the hypothesis that during stretches of maximally activated skeletal muscles, sarcomeres at longer lengths are more susceptible to damage by excessive strain.     

B-type natriuretic peptide and wall stress in dilated human heart

Background Although B-type natriuretic peptide (BNP) is used as complimentary diagnostic tool in patients with unknown thoracic disorders, many other factors appear to trigger its release. In particular, it remains unresolved to what extent cellular stretch or wall stress of the whole heart contributes to enhanced serum BNP concentration. Wall stress cannot be determined directly, but has to be calculated from wall volume, cavity volume and intraventricular pressure of the heart. The hypothesis was, therefore, addressed that wall stress as determined by cardiac magnetic resonance imaging (CMR) is the major determinant of serum BNP in patients with a varying degree of left ventricular dilatation or dysfunction (LVD). Methods A thick-walled sphere model based on volumetric analysis of the LV using CMR was compared with an echocardiography-based approach to calculate LV wall stress in 39 patients with LVD and 21 controls. Serum BNP was used as in vivo marker of a putatively raised wall stress. Nomograms of isostress lines were established to assess the extent of load reduction that is necessary to restore normal wall stress and related biochemical events. Results Both enddiastolic and endsystolic LV wall stress were correlated with the enddiastolic LV volume (r = 0.54, P < 0.001; r = 0.81, P < 0.001). LV enddiastolic wall stress was related to pulmonary pressure (capillary: r = 0.69, P < 0.001; artery: r = 0.67, P < 0.001). Although LV growth was correlated with the enddiastolic and endsystolic volume (r = 0.73, P < 0.001; r = 0.70, P < 0.001), patients with LVD exhibited increased LV wall stress indicating an inadequately enhanced LV growth. Both enddiastolic (P < 0.05) and endsystolic (P < 0.01) wall stress were increased in patients with increased BNP. In turn, BNP concentration was elevated in individuals with increased enddiastolic wall stress (>8 kPa: 587 +/- 648 pg/ml, P < 0.05; >12 kPa: 715 +/- 661 pg/ml, P < 0.001; normal < or =4 kPa: 124 +/- 203 pg/ml). Analysis of variance revealed LV enddiastolic wall stress as the only independent hemodynamic parameter influencing BNP (P < 0.01). Using nomograms with "isostress" curves, the extent of load reduction required for restoring normal LV wall stress was assessed. Compared with the CMR-based volumetric analysis for wall stress calculation, the echocardiography based approach underestimated LV wall stress particularly of dilated hearts. Conclusions In patients with LVD, serum BNP was increased over the whole range of stress values which were the only hemodynamic predictors. Cellular stretch appears to be a major trigger for BNP release. Biochemical mechanisms need to be explored which appear to operate over this wide range of wall stress values. It is concluded that the diagnostic use of BNP should primarily be directed to assess ventricular wall stress rather than the extent of functional ventricular impairment in LVD.     

Hot hypoxic flies: Whole-organism interactions between hypoxic and thermal stressors in Drosophila melanogaster

The upper critical thermal maximum (CT_max) of metazoans varies over a wide range, and its determinative factors, such as oxygen limitation, remain controversial. Induction of thermoprotective mechanisms after challenge by sublethal heat stress has been well documented in many organisms, including the model fly Drosophila melanogaster. Interestingly, however, other challenges—notably a period of anoxia—induce post-exposure thermoprotective effects in some organisms such as locusts and houseflies. Here I show, using thermolimit respirometry, that acute hypoxia during thermal stress significantly reduced the CT_max of D. melanogaster, but only below an oxygen partial pressure of about 10 kPa (39.0±0.4 SE °C at 9.3 kPa vs. 36.0±0.2 SE °C at 3.5 kPa). Likewise, the scope for voluntary motor activity declined sharply below 10 kPa and was essentially eliminated at 2.3 kPa. Respiratory water loss increased highly significantly below about 10 kPa. The post-CT_max release of a large quantity of CO₂ is shown to be independent of loss of spiracular control, but dependent at least in part on oxygen availability. The results are broadly in accord with Pörtner's oxygen limitation hypothesis, but suggest that acute oxygen limitation only becomes an important factor at partial pressures less than half of typical atmospheric levels.     

The effects of intertidal air exposure on the respiratory physiology and the killing activity of hemocytes in the pacific oyster, Crassostrea gigas (Thunberg)

The occurrence of summer mortalities of the commercially important Pacific oyster, Crassostrea gigas, has increased in recent years. These mortality events occur during the late summer when water temperatures are at their highest. Many theories have been proposed concerning the causes including reproductive stress, environmental stress, disease, or synergistic interactions of these factors. C. gigas are grown intertidally and are exposed to the air (emersed) for hours at a time. These organisms can experience extreme changes in temperature during the course of a day. An oyster closed during emersion depletes the oxygen stores to near zero within the shell and builds up CO₂ causing a decrease in tissue pH. The focus of this study is to determine the respiratory (pH, Po₂, Pco₂ and total CO₂) and immune responses of oysters exposed to air at normal seasonal temperatures, and to determine whether these stresses associated with emersion inhibit the immune system of the oyster and contribute to the summer mortalities. The respiratory variables of the hemolymph of oysters submerged at 18 °C (pH = 7.52 ± 0.04 S.E.M., Po₂ = 7.09 ± 0.53 S.E.M. kPa and Pco₂ = 0.20 ± 0.03 S.E.M. kPa) varied significantly from oysters emersed for four hours at 22°C (pH = 7.11 ± 0.03 S.E.M., Po₂ = 3.83 ± 0.15 S.E.M. kPa, Pco₂ = 0.36 ± 0.03 S.E.M. kPa) and those emersed for four hours at 30 °C (pH = 6.84 ± 0.02 S.E.M., Po₂ = 3.10 ± 0.12 S.E.M. kPa, Pco₂ = 1.31 ± 0.06 S.E.M. kPa). The ability of hemocytes to kill the bacterium Vibrio campbellii was assessed using an in vitro assay to generate a killing index. There was no significant difference in the killing index between pH treatment groups (p = 0.856): at pH 7.6 killing index = 50.2% ± 2.33 S.E.M., at pH 6.6 killing index = 52.3% ± 3.67 S.E.M.. Temperature was the only factor to significantly affect the killing indices among temperature and oxygen treatment groups. The killing index was lowest (29.3% ± 3.25 S.E.M.) at 30 °C and 7% oxygen, simulating in vivo oxygen pressure in well-aerated conditions and 30 °C and 3% oxygen, simulating in vivo oxygen pressure in hypoxia (30.5% ± 3.25 S.E.M.), compared with the index in 7% oxygen at low temperature (18 °C) (44.4% ± 4.50 S.E.M.) or compared with low oxygen (3%) at low temperature (18 °C) (39.7% ± 2.51 S.E.M.). The seasonal and diurnal rise in temperature may, therefore, be an important factor contributing to summer mortalities of C. gigas.     

Computational sensitivity investigation of hydrogel injection characteristics for myocardial support

Biomaterial injection is a potential new therapy for augmenting ventricular mechanics after myocardial infarction (MI). Recent in vivo studies have demonstrated that hydrogel injections can mitigate the adverse remodeling due to MI. More importantly, the material properties of these injections influence the efficacy of the therapy. The goal of the current study is to explore the interrelated effects of injection stiffness and injection volume on diastolic ventricular wall stress and thickness. To achieve this, finite element models were constructed with different hydrogel injection volumes (150 µL and 300 µL), where the modulus was assessed over a range of 0.1 kPa to 100 kPa (based on experimental measurements). The results indicate that a larger injection volume and higher stiffness reduce diastolic myofiber stress the most, by maintaining the wall thickness during loading. Interestingly, the efficacy begins to taper after the hydrogel injection stiffness reaches a value of 50 kPa. This computational approach could be used in the future to evaluate the optimal properties of the hydrogel.     

Tauroursodeoxycholate (TUDCA), chemical chaperone, enhances function of islets by reducing ER stress

The exposure to acute or chronic endoplasmic reticulum (ER) stress has been known to induce dysfunction of islets, leading to apoptosis. The reduction of ER stress in islet isolation for transplantation is critical for islet protection. In this study, we investigated whether tauroursodeoxycholate (TUDCA) could inhibit ER stress induced by thapsigargin, and restore the decreased glucose stimulation index of islets. In pig islets, thapsigargin decreased the insulin secretion by high glucose stimulation in a time-dependent manner (1 h, 1.35 ± 0.16; 2 h, 1.21 ± 0.13; 4 h, 1.17 ± 0.16 vs. 0 h, 1.81 ± 0.15, n = 4, p < 0.05, respectively). However, the treatment of TUDCA restored the decreased insulin secretion index induced by thapsigargin (thapsigargin, 1.25 ± 0.12 vs. thapsigargin + TUDCA, 2.13 ± 0.19, n = 5, p < 0.05). Furthermore, the culture of isolated islets for 24 h with TUDCA significantly reduced the rate of islet regression (37.4 ± 5.8% vs. 14.5 ± 6.4%, n = 12, p < 0.05). The treatment of TUDCA enhanced ATP contents in islets (27.2 ± 3.2 pmol/20IEQs vs. 21.7 ± 2.8 pmol/20IEQs, n = 9, p < 0.05). The insulin secretion index by high glucose stimulation is also increased by treatment of TUDCA (2.42 ± 0.15 vs. 1.92 ± 0.12, n = 12, p < 0.05). Taken together, we suggest that TUDCA could be a useful agent for islet protection in islet isolation for transplantation.     

Cyclic stretch-induced stress fiber dynamics - Dependence on strain rate, Rho-kinase and MLCK

Stress fiber realignment is an important adaptive response to cyclic stretch for nonmuscle cells, but the mechanism by which such reorganization occurs is not known. By analyzing stress fiber dynamics using live cell microscopy, we revealed that stress fiber reorientation perpendicular to the direction of cyclic uniaxial stretching at 1 Hz did not involve disassembly of the stress fiber distal ends located at focal adhesion sites. Instead, these distal ends were often used to assemble new stress fibers oriented progressively further away from the direction of stretch. Stress fiber disassembly and reorientation were not induced when the frequency of stretch was decreased to 0.01 Hz, however. Treatment with the Rho-kinase inhibitor Y27632 reduced stress fibers to thin fibers located in the cell periphery which bundled together to form thick fibers oriented parallel to the direction of stretching at 1 Hz. In contrast, these thin fibers remained diffuse in cells subjected to stretch at 0.01 Hz. Cyclic stretch at 1 Hz also induced actin fiber formation parallel to the direction of stretch in cells treated with the myosin light chain kinase (MLCK) inhibitor ML-7, but these fibers were located centrally rather than peripherally. These results shed new light on the mechanism by which stress fibers reorient in response to cyclic stretch in different regions of the actin cytoskeleton.     

Mechanical behavior of human aortas: Experiments,material constants and 3-D finite element modeling including residual stress

Segments of fresh human ascending, thoracic descending and abdominal aortas from eight male sexagenarians were pressurized under closed-end and free extension conditions. The median unpressurized inner radii for the ascending, thoracic and abdominal locations were 14.21, 9.67 and 7.16 mm, respectively. The median thickness was similar in the ascending and thoracic regions, at about 1.6 mm, while it was 1.2 mm in the abdominal region. The opening angle was not statistically different between regions, with a median of ?38°. Under 13.3 kPa pressure, the median circumferential stretch ratio was about 1.26 in all three aortic locations; the median longitudinal stretch ratio was similar in the ascending and thoracic regions, at about 1.13, while it was 1.05 in the abdominal region. Material constants for a three-dimensional hyperelastic anisotropic constitutive model were determined. Experimental, analytical and finite element results showed excellent agreement, validating the novel experimental approach and the numerical methods used. When residual stress was not taken into account, stresses were highest on the inside of the aorta, with a gradient across the wall of about 200 and 50 kPa in the circumferential and longitudinal directions, respectively. When residual stress was included as described by negative opening angles, stresses were highest on the outside of the aorta, with a gradient across the wall in excess of 400 kPa for the circumferential direction, and on the order of 150 kPa for the longitudinal direction. The mechanical consequences of negative opening angles had not been appreciated so far, and deserve further investigation.     

Elastic,permeability and swelling properties of human intervertebral disc tissues: A benchmark for tissue engineering

The aim of functional tissue engineering is to repair and replace tissues that have a biomechanical function, i.e., connective orthopaedic tissues. To do this, it is necessary to have accurate benchmarks for the elastic, permeability, and swelling (i.e., biphasic-swelling) properties of native tissues. However, in the case of the intervertebral disc, the biphasic-swelling properties of individual tissues reported in the literature exhibit great variation and even span several orders of magnitude. This variation is probably caused by differences in the testing protocols and the constitutive models used to analyze the data. Therefore, the objective of this study was to measure the human lumbar disc annulus fibrosus (AF), nucleus pulposus (NP), and cartilaginous endplates (CEP) biphasic-swelling properties using a consistent experimental protocol and analyses. The testing protocol was composed of a swelling period followed by multiple confined compression ramps. To analyze the confined compression data, the tissues were modeled using a biphasic-swelling model, which augments the standard biphasic model through the addition of a deformation-dependent osmotic pressure term. This model allows considering the swelling deformations and the contribution of osmotic pressure in the analysis of the experimental data. The swelling stretch was not different between the disc regions (AF: 1.28±0.16; NP: 1.73±0.74; CEP: 1.29±0.26), with a total average of 1.42. The aggregate modulus (Ha) of the extra-fibrillar matrix was higher in the CEP (390 kPa) compared to the NP (100 kPa) or AF (30 kPa). The permeability was very different across tissue regions, with the AF permeability (64 E⁻¹⁶ m⁴/N s) higher than the NP and CEP (~5.5 E⁻¹⁶ m⁴/N s). Additionally, a normalized time-constant (3000 s) for the stress relaxation was similar for all the disc tissues. The properties measured in this study are important as benchmarks for tissue engineering and for modeling the disc's mechanical behavior and transport.     

Expression and proliferation profiles of PKC,JNK and p38MAPK in physiologically stretched human bladder smooth muscle cells

Objective

To determine protein kinase C (PKC), c-Jun NH2-Terminal Kinase (JNK) and P38 mitogen-activated protein kinases (p38MAPK) expression levels and effects of their respective inhibitors on proliferation of human bladder smooth muscle cells (HBSMCs) when physiologically stretched in vitro.

Materials and methods

HBSMCs were grown on silicone membrane and stretch was applied under varying conditions; (equibiaxial elongation: 2.5%, 5%, 10%, 15%, 20%, 25%), (frequency: 0.05, 0.1, 0.2, 0.5, 1 Hz). Optimal physiological stretch was established by assessing proliferation with 5-Bromo-2-deoxyuridine (BrdU) assay and flow cytometry. PKC, JNK and p38 expression levels were analyzed by Western blot. Specificity was maintained by employing specific inhibitors; (GF109203X for PKC, SP600125 for JNK and SB203580 for p38MAPK), in some experiments.

Results

Optimum proliferation was observed at 5% equibiaxial stretch (BrdU: 0.837 ± 0.026 (control) to 1.462 ± 0.023)%, (P < 0.05) and apoptotic cell death rate decreased from 16.4 ± 0.21% (control) to 4.5 ± 0.13% (P < 0.05) applied at 0.1 Hz. Expression of PKC was upregulated with slight increase in JNK and no change in p38MAPK after application of stretch. Inhibition had effects on proliferation (1.075 ± 0.024, P < 0.05 GF109203X); (1.418 ± 0.021, P > 0.05 SP600125) and (1.461 ± 0.01, P > 0.05 SB203580). These findings show that mechanical stretch can promote magnitude-dependent proliferative modulation through PKC and possibly JNK but not via p38MAPK in hBSMCs.     

Alteration Young’s moduli by protein 4.1 phosphorylation play a potential role in the deformability development of vertebrate erythrocytes

The mechanical properties of vertebrate erythrocytes depend on their cytoskeletal protein networks. Membrane skeleton proteins spectrin and protein 4.1 (4.1R) cross-link with actin to maintain membrane stability under mechanical stress. Phosphorylation of 4.1R alters the affinity of 4.1R for spectrin–actin binding and this modulates the mechanical properties of human erythrocytes. In this study, phorbol 12-myristate-13-acetate (PMA)-induced phosphorylation of 4.1R was tested, erythrocyte deformability was determined and the erythrocyte elastic modulus was detected in human, chick, frog and fish. Furthermore, amino acid sequences of the functionally important domains of 4.1R were analyzed. Results showed that PMA-induced phosphorylation of 4.1R decreased erythrocyte deformability and this property was stable after 1 h. The values of Young’s modulus alteration gradually decreased from human to fish (0.388±0.035 kPa, 0.219±0.022 kPa, 0.191±0.036 kPa and 0.141±0.007 kPa). Ser-312 and Ser-331 are located within the consensus sequence recognized by protein kinase C (PKC); however, Ser-331 in zebrafish was replaced by Ala-331. The sequence of the 8 aa motif from vertebrate 4.1R showed only one amino acid mutation in frog and numerous substitutions in fish. Analyses of Young’s modulus suggested that the interaction between 4.1R with the spectrin–actin binding domain may have a special relationship with the development of erythrocyte deformability. In addition, amino acid mutations in 4.1R further supported this relationship. Thus, we hypothesize that alteration of membrane skeleton protein binding affinity may play a potential role in the development of erythrocyte deformability, and alteration of Young’s modulus values may provide a method for determining the deformability development of vertebrate erythrocytes.     

Effects of acute heat stress and subsequent stress removal on function of hepatic mitochondrial respiration,ROS production and lipid peroxidation in broiler chickens

In order to investigate the effects of acute heat stress and subsequent stress removal on function of hepatic mitochondrial respiration, production of reactive oxygen species (ROS) and lipid peroxidation in broiler chickens, 128 six-week-old broiler chickens were kept in a controlled-environment chamber. The broiler chickens were initially kept at 25 °C (relative humidity, RH, 70 ± 5%) for 6 d and subsequently exposed to 35 °C (RH, 70 ± 5%) for 3 h, then the heat stress was removed and the temperature returned to 25 °C (RH, 70 ± 5%). Blood and liver samples were obtained before heat exposure and at 0 (at the end of the three-hour heating episode, this group is also abbreviated as the HT group), 1, 2, 4, 8, 12 h after the stress was removed. The results showed that acute heat stress induced a significant production of ROS, function of the mitochondrial respiratory chain, antioxidative enzymes [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px)] activity, and formation of malondialdehybe (MDA). Within the first 12 h after removal of the heat stress, the acute modification of the above parameters induced by heat stress gradually approached to pre-heat levels. The results of the present study suggest that acute exposure to high temperatures may depress the activity of the mitochondrial respiratory chain. This leads to over-production of ROS, which ultimately results in lipid peroxidation and oxidative stress. When the high temperature was removed, the production of ROS, mitochondrial respiratory function and oxidative injury that were induced by acute heat exposure gradually approached the levels observed before heating, in a time-dependent manner.     

Changes in the stiffness of human mesenchymal stem cells with the progress of cell death as measured by atomic force microscopy

This note reports observations of the change of stiffness of human mesenchymal stem cells (hMSCs) with the progress of cell death as measured by AFM. hMSC with impaired membrane, dead and viable cells were labelled with Annexin V and Propidium Iodide after 24 h cold storage, followed by AFM measurement and Young's modulus of cells was derived. Viable hMSCs have a Young's modulus (E) in the range of 0.81–1.13 kPa and consistent measurement was observed when different measurement locations were chosen. E of cells with partially impaired membrane was 0.69±0.17 kPa or in the range of 2.04–4.74 kPa, depending upon the measurement locations. With the loss of membrane integrity, though there was no variation on measured E between different locations, a mixed picture of cell stiffness was observed as indicated by cells with E as low as 0.09±0.03 kPa, in a mid-range of 4.62±0.67 kPa, and the highest of up to 48.98±19.80 kPa. With the progress of cell death, the highest stiffness was noticed for cells showing a more granular appearance; also the lowest stiffness for cells with vacuole appearance. Findings from this study indicate that cell stiffness is significantly altered with the progress of cell death.     

Murine patellar tendon biomechanical properties and regional strain patterns during natural tendon-to-bone healing after acute injury

Tendon-to-bone healing following acute injury is generally poor and often fails to restore normal tendon biomechanical properties. In recent years, the murine patellar tendon (PT) has become an important model system for studying tendon healing and repair due to its genetic tractability and accessible location within the knee. However, the mechanical properties of native murine PT, specifically the regional differences in tissue strains during loading, and the biomechanical outcomes of natural PT-to-bone healing have not been well characterized. Thus, in this study, we analyzed the global biomechanical properties and regional strain patterns of both normal and naturally healing murine PT at three time points (2, 5, and 8 weeks) following acute surgical rupture of the tibial enthesis. Normal murine PT exhibited distinct regional variations in tissue strain, with the insertion region experiencing approximately 2.5 times greater strain than the midsubstance at failure (10.80±2.52% vs. 4.11±1.40%; mean±SEM). Injured tendons showed reduced structural (ultimate load and linear stiffness) and material (ultimate stress and linear modulus) properties compared to both normal and contralateral sham-operated tendons at all healing time points. Injured tendons also displayed increased local strain in the insertion region compared to contralateral shams at both physiologic and failure load levels. 93.3% of injured tendons failed at the tibial insertion, compared to only 60% and 66.7% of normal and sham tendons, respectively. These results indicate that 8 weeks of natural tendon-to-bone healing does not restore normal biomechanical function to the murine PT following injury.     

Distribution of stress and strain along the porcine aorta and coronary arterial tree

The existence of a homeostatic state of stresses and strains has been axiomatic in the cardiovascular system. The objective of this study was to determine the distribution of circumferential stress and strain along the aorta and throughout the coronary arterial tree to test this hypothesis. Silicone elastomer was perfused through the porcine aorta and coronary arterial tree to cast the arteries at physiological pressure. The loaded and zero-stress dimensions of the vessels were measured. The aorta (1.8 cm) and its secondary branches were considered down to 1.5 mm diameter. The left anterior descending artery (4.5 mm) and its branches down to 10 microm were also measured. The Cauchy mean circumferential stress and midwall stretch ratio were calculated. Our results show that the stretch ratio and Cauchy stress were lower in the thoracic than in the abdominal aorta and its secondary branches. The opening angle (theta) and midwall stretch ratio (lambda) showed a linear variation with order number (n) as follows: theta = 10.2n + 63.4 (R(2) = 0.989) and lambda = 4.47 x 10(-2)n + 1.1 (R(2) = 0.995). Finally, the stretch ratio and stress varied between 1.2 and 1.6 and between 10 and 150 kPa, respectively, along the aorta and left anterior descending arterial tree. The relative uniformity of strain (50% variation) from the proximal aorta to a 10-microm arteriole implies that the vascular system closely regulates the degree of deformation. This suggests a homeostasis of strain in the cardiovascular system, which has important implications for mechanotransduction and for vascular growth and remodeling.     

Transmural left ventricular mechanics underlying torsional recoil during relaxation

Early relaxation in the cardiac cycle is characterized by rapid torsional recoil of the left ventricular (LV) wall. To elucidate the contribution of the transmural arrangement of the myofiber to relaxation, we determined the time course of three-dimensional fiber-sheet strains in the anterior wall of five adult mongrel dogs in vivo during early relaxation with biplane cineangiography (125 Hz) of implanted transmural markers. Fiber-sheet strains were found from transmural fiber and sheet orientations directly measured in the heart tissue. The strain time course was determined during early relaxation in the epicardial, midwall, and endocardial layers referenced to the end-diastolic configuration. During early relaxation, significant circumferential stretch, wall thinning, and in-plane and transverse shear were observed (P < 0.05). We also observed significant stretch along myofibers in the epicardial layers and sheet shortening and shear in the endocardial layers (P < 0.01). Importantly, predominant epicardial stretch along the fiber direction and endocardial sheet shortening occurred during isovolumic relaxation (P < 0.05). We conclude that the LV mechanics during early relaxation involves substantial deformation of fiber and sheet structures with significant transmural heterogeneity. Predominant epicardial stretch along myofibers during isovolumic relaxation appears to drive global torsional recoil to aid early diastolic filling.     

Dependence of local left ventricular wall mechanics on myocardial fiber orientation: a model study.

The dependence of local left ventricular (LV) mechanics on myocardial muscle fiber orientation was investigated using a finite element model. In the model we have considered anisotropy of the active and passive components of myocardial tissue, dependence of active stress on time, strain and strain rate, activation sequence of the LV wall and aortic afterload. Muscle fiber orientation in the LV wall is quantified by the helix fiber angle, defined as the angle between the muscle fiber direction and the local circumferential direction. In a first simulation, a transmural variation of the helix fiber angle from +60 degrees at the endocardium through 0 degrees in the midwall layers to -60 degrees at the epicardium was assumed. In this simulation, at the equatorial level maximum active muscle fiber stress was found to vary from about 110 kPa in the subendocardial layers through about 30 kPa in the midwall layers to about 40 kPa in the subepicardial layers. Next, in a series of simulations, muscle fiber orientation was iteratively adapted until the spatial distribution of active muscle fiber stress was fairly homogeneous. Using a transmural course of the helix fiber angle of +60 degrees at the endocardium, +15 degrees in the midwall layers and -60 degrees at the epicardium, at the equatorial level maximum active muscle fiber stress varied from 52 kPa to 55 kPa, indicating a remarkable reduction of the stress range. Moreover, the change of muscle fiber strain with time was more similar in different parts of the LV wall than in the first simulation. It is concluded that (1) the distribution of active muscle fiber stress and muscle fiber strain across the LV wall is very sensitive to the transmural distribution of the helix fiber angle and (2) a physiological transmural distribution of the helix fiber angle can be found, at which active muscle fiber stress and muscle fiber strain are distributed approximately homogeneously across the LV wall.