Biomechanical characterization of tissue types in murine dissecting aneurysms based on histology and 4D ultrasound-derived strain

Abdominal aortic aneurysm disease is the local enlargement of the aorta, typically in the infrarenal section, causing up to 200,000 deaths/year. In vivo information to characterize the individual elastic properties of the aneurysm wall in terms of rupture risk is lacking. We used a method that combines 4D ultrasound and direct deformation estimation to compute in vivo 3D Green-Lagrange strain in murine angiotensin II-induced dissecting aortic aneurysms, a commonly used mouse model. After euthanasia, histological staining of cross-sectional sections along the aorta was performed in areas where in vivo strains had previously been measured. The histological sections were segmented into intact and fragmented elastin, thrombus with and without red blood cells, and outer vessel wall including the adventitia. Meshes were then created from the individual contours based on the histological segmentations. The isolated contours of the outer wall and lumen from both imaging modalities were registered individually using a coherent point drift algorithm. 2D finite element models were generated from the meshes, and the displacements from the registration were used as displacement boundaries of the lumen and wall contours. Based on the resulting deformed contours, the strains recorded were grouped according to segmented tissue regions. Strains were highest in areas containing intact elastin without thrombus attachment. Strains in areas with intact elastin and thrombus attachment, as well as areas with disrupted elastin, were significantly lower. Strains in thrombus regions with red blood cells were significantly higher compared to thrombus regions without. We then compared this analysis to statistical distribution indices and found that the results of each aligned, elucidating the relationship between vessel strain and structural changes. This work demonstrates the possibility of advancing in vivo assessments to a microstructural level ultimately improving patient outcomes.

     

Stereoscopically observed deformations of a compliant abdominal aortic aneurysm model

A new experimental setup has been implemented to precisely measure the deformations of an entire model abdominal aortic aneurysm (AAA). This setup addresses a gap between the computational and experimental models of AAA that have aimed at improving the limited understanding of aneurysm development and rupture. The experimental validation of the deformations from computational approaches has been limited by a lack of consideration of the large and varied deformations that AAAs undergo in response to physiologic flow and pressure. To address the issue of experimentally validating these calculated deformations, a stereoscopic imaging system utilizing two cameras was constructed to measure model aneurysm displacement in response to pressurization. The three model shapes, consisting of a healthy aorta, an AAA with bifurcation, and an AAA without bifurcation, were also evaluated with computational solid mechanical modeling using finite elements to assess the impact of differences between material properties and for comparison against the experimental inflations. The device demonstrated adequate accuracy (surface points were located to within 0.07?mm) for capturing local variation while allowing the full length of the aneurysm sac to be observed at once. The experimental model AAA demonstrated realistic aneurysm behavior by having cyclic strains consistent with reported clinical observations between pressures 80 and 120?mm Hg. These strains are 1-2%, and the local spatial variations in experimental strain were less than predicted by the computational models. The three different models demonstrated that the asymmetric bifurcation creates displacement differences but not cyclic strain differences within the aneurysm sac. The technique and device captured regional variations of strain that are unobservable with diameter measures alone. It also allowed the calculation of local strain and removed rigid body motion effects on the strain calculation. The results of the computations show that an asymmetric aortic bifurcation created displacement differences but not cyclic strain differences within the aneurysm sac.     

Investigation of material modeling in fluid–structure interaction analysis of an idealized three-layered abdominal aorta: aneurysm initiation and fully developed aneurysms

Different material models for an idealized three-layered abdominal aorta are compared using computational techniques to study aneurysm initiation and fully developed aneurysms. The computational model includes fluid–structure interaction (FSI) between the blood vessel and the blood. In order to model aneurysm initiation, the medial region was degenerated to mimic the medial loss occurring in the inception of an aneurysm. Various cases are considered in order to understand their effects on the initiation of an abdominal aortic aneurysm. The layers of the blood vessel were modeled using either linear elastic materials or Mooney–Rivlin (otherwise known as hyperelastic) type materials. The degenerated medial region was also modeled in either linear elastic or hyperelastic-type materials and assumed to be in the shape of an arc with a thin width or a circular ring with different widths. The blood viscosity effect was also considered in the initiation mechanism. In addition, dynamic analysis of the blood vessel was performed without interaction with the blood flow by applying time-dependent pressure inside the lumen in a three-layered abdominal aorta. The stresses, strains, and displacements were compared for a healthy aorta, an initiated aneurysm and a fully developed aneurysm. The study shows that the material modeling of the vessel has a sizable effect on aneurysm initiation and fully developed aneurysms. Different material modeling of degeneration regions also affects the stress–strain response of aneurysm initiation. Additionally, the structural analysis without considering FSI (called noFSI) overestimates the peak von Mises stress by 52% at the interfaces of the layers.     

Effects of wall calcifications in patient-specific wall stress analyses of abdominal aortic aneurysms

It is generally acknowledged that rupture of an abdominal aortic aneurysm (AAA) occurs when the stress acting on the wall over the cardiac cycle exceeds the strength of the wall. Peak wall stress computations appear to give a more accurate rupture risk assessment than AAA diameter, which is currently used for a diagnosis. Despite the numerous studies utilizing patient-specific wall stress modeling of AAAs, none investigated the effect of wall calcifications on wall stress. The objective of this study was to evaluate the influence of calcifications on patient-specific finite element stress computations. In addition, we assessed whether the effect of calcifications could be predicted directly from the CT-scans by relating the effect to the amount of calcification present in the AAA wall. For 6 AAAs, the location and extent of calcification was identified from CT-scans. A finite element model was created for each AAA and the areas of calcification were defined node-wise in the mesh of the model. Comparisons are made between maximum principal stress distributions, computed without calcifications and with calcifications with varying material properties. Peak stresses are determined from the stress results and related to a calcification index (CI), a quantification of the amount of calcification in the AAA wall. At calcification sites, local stresses increased, leading to a peak stress increase of 22% in the most severe case. Our results displayed a weak correlation between the CI and the increase in peak stress. Additionally, the results showed a marked influence of the calcification elastic modulus on computed stresses. Inclusion of calcifications in finite element analysis of AAAs resulted in a marked alteration of the stress distributions and should therefore be included in rupture risk assessment. The results also suggest that the location and shape of the calcified regions--not only the relative amount--are considerations that influence the effect on AAA wall stress. The dependency of the effect of the wall stress on the calcification elastic modulus points out the importance of determination of the material properties of calcified AAA wall.     

Functional MRI can detect changes in intratissue strains in a full thickness and critical sized ovine cartilage defect model

Functional imaging of tissue biomechanics can reveal subtle changes in local softening and stiffening associated with disease or repair, but noninvasive and nondestructive methods to acquire intratissue measures in well-defined animal models are largely lacking. We utilized displacement encoded MRI to measure changes in cartilage deformation following creation of a critical-sized defect in the medial femoral condyle of ovine (sheep) knees, a common in situ and large animal model of tissue damage and repair. We prioritized visualization of local, site-specific variation and changes in displacements and strains following defect placement by measuring spatial maps of intratissue deformation. Custom data smoothing algorithms were developed to minimize propagation of noise in the acquired MRI phase data toward calculated displacement or strain, and to improve strain measures in high aspect ratio tissue regions. Strain magnitudes in the femoral, but not tibial, cartilage dramatically increased in load-bearing and contact regions especially near the defect locations, with an average 6.7% ± 6.3%, 13.4% ± 10.0%, and 10.0% ± 4.9% increase in first and second principal strains, and shear strain, respectively. Strain heterogeneity reflected the complexity of the in situ mechanical environment within the joint, with multiple tissue contacts defining the deformation behavior. This study demonstrates the utility of displacement encoded MRI to detect increased deformation patterns and strain following disruption to the cartilage structure in a clinically-relevant, large animal defect model. It also defines imaging biomarkers based on biomechanical measures, in particular shear strain, that are potentially most sensitive to evaluate damage and repair, and that may additionally translate to humans in future studies.     

Performance Comparison of Ultrasound-Based Methods to Assess Aortic Diameter and Stiffness in Normal and Aneurysmal Mice

Objective

Several ultrasound-based methods are currently used to assess aortic diameter, circumferential strain and stiffness in mice, but none of them is flawless and a gold standard is lacking. We aimed to assess the validity and sensitivity of these methods in control animals and animals developing dissecting abdominal aortic aneurysm.

Methods and Results

We first compared systolic and diastolic diameters as well as local circumferential strains obtained in 47 Angiotensin II-infused ApoE ^-/- mice with three different techniques (BMode, short axis MMode, long axis MMode), at two different abdominal aortic locations (supraceliac and paravisceral), and at three different time points of abdominal aneurysm formation (baseline, 14 days and 28 days). We found that short axis BMode was preferred to assess diameters, but should be avoided for strains. Short axis MMode gave good results for diameters but high standard deviations for strains. Long axis MMode should be avoided for diameters, and was comparable to short axis MMode for strains. We then compared pulse wave velocity measurements using global, ultrasound-based transit time or regional, pressure-based transit time in 10 control and 20 angiotensin II-infused, anti-TGF-Beta injected C57BL/6 mice. Both transit-time methods poorly correlated and were not able to detect a significant difference in PWV between controls and aneurysms. However, a combination of invasive pressure and MMode diameter, based on radio-frequency data, detected a highly significant difference in local aortic stiffness between controls and aneurysms, with low standard deviation.

Conclusions

In small animal ultrasound the short axis view is preferred over the long axis view to measure aortic diameters, local methods are preferred over transit-time methods to measure aortic stiffness, invasive pressure-diameter data are preferred over non-invasive strains to measure local aortic stiffness, and the use of radiofrequency data improves the accuracy of diameter, strain as well as stiffness measurements.     

3D characterization of bone strains in the rat tibia loading model

Bone strain is considered one of the factors inducing bone tissue response to loading. Nevertheless, where animal studies can provide detailed data on bone response, they only offer limited information on experimental bone strains. Including micro-CT-based finite element (micro FE) models in the analysis represents a potent methodology for quantifying strains in bone. Therefore, the main objective of this study was to develop and validate specimen-specific micro FE models for the assessment of bone strains in the rat tibia compression model. Eight rat limbs were subjected to axial compression loading; strain at the medio-proximal site of the tibiae was measured by means of strain gauges. Specimen-specific micro FE models were created and analyzed. Repeated measurements on each limb indicated that the effect of limb positioning was small (COV?= 6.45 ± 2.27 %). Instead, the difference in the measured strains between the animals was high (54.2%). The computational strains calculated at the strain gauge site highly correlated to the measured strains (R ²?=?0.95). Maximum peak strains calculated at exactly 25% of the tibia length for all specimens were equal to 435.11 ± 77.88 microstrains (COV?=?17.19%). In conclusion, we showed that strain gauge measurements are very sensitive to the exact strain gauge location on the bone; hence, the use of strain gauge data only is not recommended for studies that address at identifying reliable relationships between tissue response and local strains. Instead, specimen-specific micro FE models of rat tibiae provide accurate estimates of tissue-level strains.     

Stress fibers of the aortic smooth muscle cells in tissues do not align with the principal strain direction during intraluminal pressurization

Stress fibers (SFs) in cells transmit external forces to cell nuclei, altering the DNA structure, gene expression, and cell activity. To determine whether SFs are involved in mechanosignal transduction upon intraluminal pressure, this study investigated the SF direction in smooth muscle cells (SMCs) in aortic tissue and strain in the SF direction. Aortic tissues were fixed under physiological pressure of 120 mmHg. First, we observed fluorescently labeled SFs using two-photon microscopy. It was revealed that SFs in the same smooth muscle layers were aligned in almost the same direction, and the absolute value of the alignment angle from the circumferential direction was 16.8° ± 5.2° (n = 96, mean ± SD). Second, we quantified the strain field in the aortic tissue in reference to photo-bleached markers. It was found in the radial-circumferential plane that the largest strain direction was − 21.3° ± 11.1°, and the zero normal strain direction was 28.1° ± 10.2°. Thus, the SFs in aortic SMCs were not in line with neither the largest strain direction nor the zero strain direction, although their orientation was relatively close to the zero strain direction. These results suggest that SFs in aortic SMCs undergo stretch, but not maximal and transmit the force to nuclei under intraluminal pressure.

     

Aortic Elasticity is Impaired in Patients with Endemic Fluorosis

Sixty-three patients with endemic fluorosis (36 males/27 females; mean age 33.9 ± 8.6 years) and 45 age-, sex-, and body mass index-matched healthy controls (30 males/15 females; mean age 32.7 ± 8.8 years) were included in this study. Aortic stiffness indices, aortic strain (AS), aortic distensibility (AD), and aortic strain index (ASI) were calculated from the aortic diameters measured by echocardiography and blood pressure obtained by sphygmomanometry. The urine fluoride levels of fluorosis patients were significantly higher than control subjects as expected (1.9 ± 0.1 mg/l vs. 0.4 ± 0.1 mg/l, respectively; P < 0.001). AS and AD were significantly lower in fluorosis patients than in the controls (for AS 5.3 ± 3.6 vs. 8.0 ± 3.4%; P < 0.001 and for AD 0.2 ± 0.1 vs. 0.3 ± 0.1 cm² dyn⁻¹ 10⁻³; P < 0.001, respectively). In contrast, signicantly higher ASI was observed in fluorosis patients than in the controls (3.4 ± 0.6 vs. 3.0 ± 0.4; P < 0.001, respectively). The results of our study demonstrate that elastic properties of ascending aorta are impaired in patients with endemic fluorosis.     

Giemsa-based cytological assessment of area,shape and nucleus:cytoplasm ratio of goblet cells of rabbit bulbar conjunctiva

Goblet cells were visualized in impression cytology specimens from bulbar conjunctiva of the rabbit eye using Giemsa staining. Highly magnified images were used to generate outlines of the goblet cells and their characteristic eccentric nuclei. Using sets of 10 cells from 15 cytology specimens, I found that the longest dimension of the goblet cells averaged 16.7 ± 2.3 μm, the shortest dimension averaged 14.4 ± 1.8 μm and the nucleus averaged 6.3 ± 0.8 μm. The goblet cells were ellipsoid in shape and the longest:shortest cell dimension ratio averaged 1.169 ± 0.091. The goblet cell areas ranged from 108 to 338 μm² (average 193 ± 50 μm²). The area could be predicted reliably from the longest and shortest dimensions (r² = 0.903). The areas of goblet cell nuclei were 15–58 μm² (average 33 ± μm²) and the nucleus:cytoplasm area fraction was predictably greater in smaller goblet cells and less in the larger goblet cells (Spearman correlation = 0.817). The nuclei were estimated to occupy an average of 9.5% of the cell volume. The differences in size, shape and nucleus:cytoplasm ratio may reflect differences in goblet cell maturation.     

An in vitro model quantifying the effect of calcification on the tissue–stent interaction in a stenosed aortic root

Transcatheter Aortic Valves rely on the tissue-stent interaction to ensure that the valve is secured within the aortic root. Aortic stenosis presents with heavily calcified leaflets and it has been proposed that this calcification also acts to secure the valve, but this has never been quantified. In this study, we developed an in vitro calcified aortic root model to quantify the role of calcification on the tissue-stent interaction. The in vitro model incorporated artificial calcifications affixed to the leaflets of porcine aortic heart valves. A self-expanding nitinol braided stent was deployed into non-calcified and artificially calcified porcine aortic roots and imaged by micro computed tomography. Mechanical tests were then conducted to dislodge the stent from the aortic root and it was found that, in the presence of calcification, there was a significant increase in pullout force (8.59 ± 3.68 N vs. 2.84 ± 1.55 N p = 0.045), stent eccentricity (0.05 ± 0.01 vs. 0.02 ± 0.01, p = 0.049), and coefficient of friction between the stent and aortic root (0.36 ± 0.12 vs. 0.09 ± 0.05, p = 0.018), when compared to non-calcified roots. This study quantifies for the first time the impact of calcification on the friction between the aortic tissue and transcatheter aortic valve stent, showing the role of calcification in anchoring the valve stent in the aortic root.     

Scanner influence on the mechanical response of QCT-based finite element analysis of long bones

Patient-specific QCT-based finite element (QCTFE) analyses enable highly accurate quantification of bone strength. We evaluated CT scanner influence on QCTFE models of long bones.A femur, humerus, and proximal femur without the head were scanned with K₂HPO₄ phantoms by seven CT scanners (four models) using typical clinical protocols. QCTFE models were constructed. The geometrical dimensions, as well as the QCT-values expressed in Hounsfield unit (HU) distribution was compared. Principal strains at representative regions of interest (ROIs), and maximum principal strains (associated with fracture risk) were compared. Intraclass correlation coefficients (ICCs) were calculated to evaluate strain prediction reliability for different scanners. Repeatability was examined by scanning the femur twice and comparing resulting QCTFE models.Maximum difference in geometry was 2.3%. HU histograms before phantom calibration showed wide variation between QCT scans; however, bone density histogram variability was reduced after calibration and algorithmic manipulation. Relative standard deviation (RSD) in principal strains at ROIs was <10.7%. ICC estimates between scanners were >0.9. Fracture-associated strain had 6.7%, 8.1%, and 13.3% maximum RSD for the femur, humerus, and proximal femur, respectively. The difference in maximum strain location was <2 mm. The average difference with repeat scans was 2.7%.Quantification of strain differences showed mean RSD bounded by ∼6% in ROIs. Fracture-associated strains in “regular” bones showed a mean RSD bounded by ∼8%. Strains were obtained within a ±10% difference relative to the mean; thus, in a longitudinal study only changes larger than 20% in the principal strains may be significant. ICCs indicated high reliability of QCTFE models derived from different scanners.     

PHILOS钢板治疗老年肱骨近端冠状面骨折初探

目的:探讨采用PHILOS钢板治疗肱骨近端冠状面骨折手术治疗的早期临床疗效。方法:对2005年4月至2014年5月我院收治的9例肱骨近端冠状面骨折患者予以切开复位钢内固定治疗,采用DASH评分,生活质量评价量表(SF-36),Constant-Murley评分以及加利福尼亚洛杉矶大学肩关节评分(UCLA Score)对患者进行功能评价。结果:纳入患者平均年龄为63.5±3.2岁(53~82岁),男性2例,女性7例,根据Neer分型,单纯二部分骨折5例,二部分骨折伴肩关节脱位4例。术后随访12~22个月,平均14.2±3.2个月。9例患者均得到随访。所有患者肱骨近端骨折均愈合,骨折愈合时间12~18周,平均12.7±2.5周,末次随访时,7例无明显肩关节疼痛,2例有轻微疼痛,Constant评分平均87.0±4.2分;DASH评分平均20.9±2.5分,加州大学肩关节评分系统(UCLA)平均31.3±2.1;SF-36评分平均分,影像学结果显示:末次随访肱骨头高度平均丢失1.7±0.4 mm,颈干角度平均为126±13°。结论:采用切开复位钢板内固定对于肱骨近端冠状面骨折早期临床疗效良好,远期疗效有待进一步评价。     

An in vitro investigation of the inflammatory response to the strain amplitudes which occur during high frequency oscillation ventilation and conventional mechanical ventilation

Children randomised in the neonatal period to high frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CMV) in the United Kingdom Oscillation study (UKOS) had superior lung function at 11 to 14 years of age. During HFOV, much smaller tidal volumes, but a higher mean airway distending pressure is delivered, hence, a possible explanation for a volume dependent effect on long term lung function could be an increase in inflammation in response to higher tidal volumes and strains. We tested that hypothesis by assessing interleukin-6 (IL-6) and -8 (IL-8) release from A549 alveolar analogue cells following biaxial mechanical strain applied at 0.5 Hz occurring during conditions mimicking strain during CMV (5–20% strain) and conditions mimicking strain during HFOV (17.5% ± 2.5% strain) for up to 4 h. Cyclic strain of 5–20%, occurring during CMV, increased levels of both IL-6 and IL-8 compared to unstrained controls, while 17.5% ± 2.5% strain, occurring during HFOV, was associated with significantly lower levels of IL-6 (46.31 ± 2.66 versus 56.79 ± 3.73 pg/mL) and IL-8 (1340.2 ± 74.9 versus 2522 ± 248 pg/mL) secretion compared to conditions occurring during CMV at four hours. These results may provide a possible explanation for the superior lung function in 11–14-year-old children who had been supported in the neonatal period by HFOV.     

Estimation of in vivo inter-vertebral loading during motion using fluoroscopic and magnetic resonance image informed finite element models

Finite element (FE) models driven by medical image data can be used to estimate subject-specific spinal biomechanics. This study aimed to combine magnetic resonance (MR) imaging and quantitative fluoroscopy (QF) in subject-specific FE models of upright standing, flexion and extension. Supine MR images of the lumbar spine were acquired from healthy participants using a 0.5 T MR scanner. Nine 3D quasi-static linear FE models of L3 to L5 were created with an elastic nucleus and orthotropic annulus. QF data was acquired from the same participants who performed trunk flexion to 60° and trunk extension to 20°. The displacements and rotations of the vertebrae were calculated and applied to the FE model. Stresses were averaged across the nucleus region and transformed to the disc co-ordinate system (S1 = mediolateral, S2 = anteroposterior, S3 = axial). In upright standing S3 was predicted to be −0.7 ± 0.6 MPa (L3L4) and −0.6 ± 0.5 MPa (L4L5). S3 increased to −2.0 ± 1.3 MPa (L3L4) and −1.2 ± 0.6 MPa (L4L5) in full flexion and to −1.1 ± 0.8 MPa (L3L4) and −0.7 ± 0.5 MPa (L4L5) in full extension. S1 and S2 followed similar patterns; shear was small apart from S23. Disc stresses correlated to disc orientation and wedging. The results demonstrate that MR and QF data can be combined in a participant-specific FE model to investigate spinal biomechanics in vivo and that predicted stresses are within ranges reported in the literature.     

A reproducible swine model of a surgically created saccular thoracic aortic aneurysm

A reproducible swine thoracic aortic aneurysm (TAA) model is useful for investigating new therapeutic interventions. We report a surgical method for creating a reproducible swine saccular TAA model. We used eight female swine weighing 20–25 kg (LWD; ternary species). All procedures were performed under general anesthesia and involved left thoracotomy. Following aortic cross-clamping, the thoracic aorta was surgically dissected and the media and intima were resected, and the dissection plane was extended by spreading the outer layer for aneurysmal space. Subsequently, only the adventitial layer of the aorta was sutured. At 2 weeks after these procedures, angiography and computed tomography were performed. After follow-up imaging, the model animals were euthanized. Macroscopic, histological, and immunohistological examinations were performed. All model animals survived, and a saccular TAA was confirmed by follow-up imaging in all cases. The mean length of the shorter and the longer aortic diameter after the procedure were 14.01 ± 1.0 mm and 18.35 ± 1.4 mm, respectively (P<0.001). The rate of increase in the aortic diameter was 131.7 ± 13.8%, and the mean length of aneurysmal change at thoracic aorta was 22.4 ± 1.9 mm. Histological examination revealed intimal tears and defects of elastic fibers in the media. Immunostaining revealed MMP-2 and MMP-9 expressions at the aneurysm site. We report our surgical method for creating a swine saccular TAA model. Our model animal may be useful to investigate new therapeutic interventions for aortic disease.     

Including surrounding tissue improves ultrasound-based 3D mechanical characterization of abdominal aortic aneurysms

ObjectivesIn this study the influence of surrounding tissues including the presence of the spine on wall stress analysis and mechanical characterization of abdominal aortic aneurysms using ultrasound imaging has been investigated.MethodsGeometries of 7 AAA patients and 11 healthy volunteers were acquired using 3-D ultrasound and converted to finite element based models. Model complexity of externally unsupported (aorta-only) models was complemented with inclusion of both soft tissue around the aorta and a spine support dorsal to the aorta. Computed 3-D motion of the aortic wall was verified by means of ultrasound speckle tracking. Resulting stress, strain, and estimated shear moduli were analyzed to quantify the effect of adding surrounding material supports.ResultsAn improved agreement was shown between the ultrasound measurements and the finite element tissue and spine models compared to the aorta-only models. Peak and 99-percentile Von Mises stress showed an overall decrease of 23–30%, while estimated shear modulus decreased with 12–20% after addition of the soft tissue. Shear strains in the aortic wall were higher in areas close to the spine compared to the anterior region.ConclusionsImproving model complexity with surrounding tissue and spine showed a homogenization of wall stresses, reduction in homogeneity of shear strain at the posterior side of the AAA, and a decrease in estimated aortic wall shear modulus. Future research will focus on the importance of a patient-specific spine geometry and location.     

Aortic valve leaflet mechanical properties facilitate diastolic valve function

This work was concerned with the numerical simulation of the behaviour of aortic valves whose material can be modelled as non-linear elastic anisotropic. Linear elastic models for the valve leaflets with parameters used in previous studies were compared with hyperelastic models, incorporating leaflet anisotropy with pronounced stiffness in the circumferential direction through a transverse isotropic model. The parameters for the hyperelastic models were obtained from fits to results of orthogonal uniaxial tensile tests on porcine aortic valve leaflets. The computational results indicated the significant impact of transverse isotropy and hyperelastic effects on leaflet mechanics; in particular, increased coaptation with peak values of stress and strain in the elastic limit. The alignment of maximum principal stresses in all models follows approximately the coarse collagen fibre distribution found in aortic valve leaflets. The non-linear elastic leaflets also demonstrated more evenly distributed stress and strain which appears relevant to long-term scaffold stability and mechanotransduction.     

The Asp298 allele of endothelial nitric oxide synthase is a risk factor for myocardial infarction among patients with type 2 diabetes mellitus

Background

To establish an efficient prophylaxis of coronary artery disease reliable risk stratification is crucial, especially in the high risk population of patients suffering from diabetes mellitus. This prospective study determined the predictive value of coronary calcifications for future cardiovascular events in asymptomatic patients with diabetes mellitus.

Methods

We included 716 patients suffering from diabetes mellitus (430 men, 286 women, age 55.2 ± 15.2 years) in this study. On study entry all patients were asymptomatic and had no history of coronary artery disease. In addition, all patients showed no signs of coronary artery disease in ECG, stress ECG or echocardiography. Coronary calcifications were determined with the Imatron C 150 XP electron beam computed tomograph. For quantification of coronary calcifications we calculated the Agatston score. After a mean observation period of 8.1 ± 1.1 years patients were contacted and the event rate of cardiac death (CD) and myocardial infarction (MI) was determined.

Results

During the observation period 40 patients suffered from MI, 36 patients died from acute CD. The initial Agatston score in patients that suffered from MI or died from CD (475 ± 208) was significantly higher compared to those without cardiac events (236 ± 199, p < 0.01). An Agatston score above 400 was associated with a significantly higher annualised event rate for cardiovascular events (5.6% versus 0.7%, p < 0.01). No cardiac events were observed in patients with exclusion of coronary calcifications. Compared to the Framingham risk score and the UKPDS score the Agatston score showed a significantly higher diagnostic accuracy in the prediction of MI with an area under the ROC curve of 0.77 versus 0.68, and 0.71, respectively, p < 0.01.

Conclusion

By determination of coronary calcifications patients at risk for future MI and CD could be identified within an asymptomatic high risk group of patients suffering from diabetes mellitus. On the other hand future events could be excluded in patients without coronary calcifications.