Biomechanical characterization and constitutive modeling of the layer-dissected residual strains and mechanical properties of abdominal porcine aorta.

We analyze the residual stresses and mechanical properties of layer-dissected infrarenal abdominal aorta (IAA). We measured the axial pre-stretch and opening angle and performed uniaxial tests to study and compare the mechanical behavior of both intact and layer-dissected porcine IAA samples under physiological loads. Finally, some of the most popular anisotropic hyperelastic constitutive models (GOH and microfiber models) were proposed to estimate the mechanical properties of the abdominal aorta by least-square fitting of the recorded in-vitro uniaxial test results. The results show that the residual stresses are layer dependent. In all cases, we found that the OA in the media layer is lower than in the whole artery, the intima and the adventitia. For the axial pre-stretch, we found that the adventitia and the media were slightly stretched in the environment of the intact arterial strip, whereas the intima appears to be compressed. Regarding the mechanical properties, the media seems to be the softest layer over the whole deformation domain showing high anisotropy, while the intima and adventitia exhibit considerable stiffness and a lower anisotropy response. Finally, all the hyperelastic anisotropic models considered in this study provided a reasonable approximation of the experimental data. The GOH model showed the best fitting.

A parametric model for studying the aorta hemodynamics by means of the computational fluid dynamics.

Perturbed aorta hemodynamics, as for the carotid and the coronary artery, has been identified as potential predicting factor for cardiovascular diseases. In this study, we propose a parametric study based on the computational fluid dynamics with the aim of providing information regarding aortic disease. In particular, the blood flow inside a parametrized aortic arch is computed as a function of morphological changes of baseline aorta geometry. Flow patterns, wall shear stress, time average wall shear stress and oscillatory shear index were calculated during the cardiac cycle. The influence of geometrical changes on the hemodynamics and on these variables was evaluated. The results suggest that the distance between inflow and aortic arch and the angle between aortic arch and descending trunk are the most influencing parameters regarding the WSS-related indices while the effect of the inlet diameter seems limited. In particular, an increase of the aforementioned distance produces a reduction of the spatial distribution of the higher values of the time average wall shear stress and of the oscillatory shear index independently on the other two parameters while an increase of the angle produce an opposite effect. Moreover, as expected, the analysis of the wall shear stress descriptors suggests that the inlet diameter influences only the flow intensity. As conclusion, the proposed parametric study can be used to evaluate the aorta hemodynamics and could be also applied in the future, for analyzing pathological cases and virtual situations, such as pre- and/or post-operative cardiovascular surgical states that present enhanced changes in the aorta morphology yet promoting important variations on the considered indexes.

Effect of Diet and Age on Arterial Stiffening Due to Atherosclerosis in ApoE(-/-) Mice.

This work analyzes the progressive stiffening of the aorta due to atherosclerosis development of both ApoE(-/-) and C57BL/6J mice fed on a Western (n = 5) and a normal (n = 5) chow diet for the ApoE(-/-) group and on a normal chow diet (n = 5) for the C57BL/6J group. Sets of 5 animals from the three groups were killed after 10, 20, 30 and 40 weeks on their respective diets (corresponding to 17, 27, 37 and 47 weeks of age). Mechanical properties (inflation test and axial residual stress measurements) and histological properties were compared for both strains, ApoE(-/-) on the hyper-lipidic diet and both ApoE(-/-) and C57BL/6J on the normal diet, after the same period and after different periods of diet. The results indicated that the aorta stiffness in the ApoE(-/-) and C57BL/6J mice under normal diet remained approximately constant irrespective of their age. However, the arterial stiffness in the ApoE(-/-) on the hyper-lipidic diet increased over time. Statistical differences were found between the group after 10 weeks and the groups after 30 and 40 weeks of a hyper-lipidic diet. Comparing the hyper-lipidic and normal diet mice, statistical differences were also found between both diets in all cases after 40 weeks of diet, frequently after 30 weeks, and in some cases after 20 weeks. The early stages of lesion corresponded to the first 2 weeks of diet. Advanced lesions were found at 30 weeks and, finally, the aorta was completely damaged after 40 weeks of diet. In conclusion, we found substantial changes in the mechanical properties of the aorta walls of the ApoE(-/-) mice fed with the hyper-lipidic diet compared to the normal chow diet groups for both the ApoE(-/-) and C57BL/6J groups. These findings could serve as a reference for the study of changes in the arterial wall properties in cases of atherosclerosis.

Effect of Transmural Transport Properties on Atheroma Plaque Formation and Development.

We propose a mathematical model of atheroma plaque initiation and early development in coronary arteries using anisotropic transmural diffusion properties. Our current approach is on the process on plaque initiation and intimal thickening rather than in severe plaque progression and rupture phenomena. The effect of transport properties, in particular the anisotropy of diffusion properties of the artery, on plaque formation and development is investigated using the proposed mathematical model. There is not a strong influence of the anisotropic transmural properties on LDL, SMCs and collagen distribution and concentrations along the artery. On the contrary, foam cells distribution strongly depends on the value of the radial diffusion coefficient of the substances [Formula: see text] and the ratio [Formula: see text]. Decreasing [Formula: see text] or diffusion coefficients ratio means a higher concentration of the foam cells close to the intima. Due to the fact that foam cells concentration is associated to the necrotic core formation, the final distribution of foam cells is critical to evolve into a vulnerable or fibrotic plaque.

Comparison of the vulnerability risk for positive versus negative atheroma plaque morphology.

As plaque develops in arteries two types of remodeling can occur; positive and negative remodeling. Positive remodeling is an outward compensatory remodeling in which the arterial wall grows outward in an attempt to maintain a constant lumen diameter, while negative remodeling is defined as a local shrinkage of vessel size. Sudden heart attacks remain one of the primary causes of premature death in the developed world. The role of positive remodeling in vulnerable plaque rupture mechanics, which could explain why many of these heart attacks occur without prior symptoms, is still debated. In this manuscript we present a numerical study of the role of vascular growth on plaque vulnerability. Plane strain finite element models of a coronary artery with positive and negative morphology have been compared by systematically varying the most influential values of the geometry of the vessel on plaque stresses: (i) the fibrous cap thickness, (ii) the stenosis ratio, (iii) the lipid core dimensions and (iv) the atheroma plaque distribution (eccentric or concentric). All models have been developed with the same average dimensions and material properties. Vessel wall stress concentrations were always predicted to be higher in the fibrous cap of atheroma plaques with positive morphology compared to those with negative morphology. Furthermore, our conclusions are independent of the fibrous cap and the degree of stenosis considered. These results may explain why plaque rupture is often apparent at sites with only modest luminal stenoses but marked positive remodeling. The results of this study support the hypothesis that coronary arteries with positive remodeling are more vulnerable to rupture than those arteries with negative remodeling for comparable geometrical conditions.

3D computational parametric analysis of eccentric atheroma plaque: influence of axial and circumferential residual stresses.

Plaque rupture plays a role in the majority of acute coronary syndromes. Rupture has usually been associated with stress concentrations, which are mainly affected by the plaque geometry and the tissue properties. The aim of this study is to evaluate the influence of morphology on the risk of plaque rupture, including the main geometrical factors, and to assess the role of circumferential and axial residual stresses by means of a parametric 3D finite element model. For this purpose, a 3D parametric finite element model of the coronary artery with eccentric atheroma plaque was developed. Healthy (adventitia and media in areas without atheroma plaque) and diseased (fibrotic and lipidic) tissues were considered in the model. The geometrical parameters used to define and design the idealized coronary plaque anatomy were the lipid core length, the stenosis ratio, the fibrous cap thickness, and the lipid core ratio. Finally, residual stresses in longitudinal and circumferential directions were incorporated into the model to analyse the influence of the important mechanical factors in the vulnerability of the plaque. Viewing the results, we conclude that residual stresses should be considered in the modelling of this kind of problems since they cause a significant alteration of the vulnerable plaque region limits. The obtained results show that the fibrous cap thickness and the lipid core length, in combination with the lipid core width, appear to be the key morphological parameters that play a determinant role in the maximal principal stress (MPS). However, the stenosis ratio is found to not play a significant role in vulnerability related to the MPS. Plaque rupture should therefore be observed as a consequence, not only of the cap thickness, but as a combination of the stenosis ratio, the fibrous cap thickness and the lipid core dimensions.

Adult stem cells: perspectives for therapeutic applications.

The use of adult stem cells in tissue regeneration appears to be a powerful research tool, due to the intrinsic characteristics of these cells, i.e., self-renewal and unlimited capacity for proliferation. In particular, mesenchymal stem cells (MSCs) obtained from bone marrow or peripheral blood can be easily isolated, cultivated, propagated and can be differentiated into several specialized cell types thanks to their plasticity. Among these cells, MSCs can evolve into cardiac cell lineages. Since heart damage leads to the irreversible loss of cardiac function, cell transplantation could be a potential therapy for heart injury. Our laboratory has focused on the purification and expansion of rat and sheep MSCs, their differentiation into cardiomyocytes and their characterisation. Numerous results indicate that MSCs could be promising for therapy, however we need to better understand the biology of stem cells to improve methods for delivery and/or pharmacological activation. These techniques can indeed track engrafted cells and systems to guarantee their safe use.

Audit of deaths less than a week after admission through an emergency department: how accurate was the ED diagnosis and were any deaths preventable?

AIM: To review the causes of death in patients admitted via the emergency department (ED) who died within 7 days of admission and to identify any ways in which ED care could have been better. The study also aims to compare the diagnosis made in the ED and the mortality diagnosis. METHODS: A retrospective study; subjects were all patients who attended the ED over 4 months and died within 7 days of admission. The paramedics' notes, ED case cards, inpatient medical notes and details of postmortem findings were examined to identify the time and date of arrival in the ED, presenting complaint, provisional diagnosis made by the ED, treatment plan devised by the ED, diagnosis made in wards, and the cause of death as issued on death certificates or from postmortem findings. Summary sheets of cases where the care provided by the emergency department could have been improved were reviewed, errors were identified and deaths were classified as preventable or unpreventable. RESULTS: Database revealed 3521 admissions via the ED over 4 months, of which 95 cases (2.69%) died within 7 days of admission. 78 patients (82.1% of cases) were appropriately diagnosed and managed whereas 17 (17.87% of cases) were identified with deficiencies in either the diagnosis or the management provided in the ED. We reviewed the quality of care provided in the ED for these cases and rated deaths according to our preventability criteria: 5 (5.26%) deaths were unpreventable despite the deficiency in care provided in the ED; 3 (3.15%) deaths were definitely preventable; 3 (3.15%) were probably preventable; and 6 (6.31%) were possibly preventable deaths. CONCLUSION: The ED is playing a good role in the management of critically ill patients, with appropriate diagnosis and management in 82% of cases. Training of junior doctors is required to prevent occurrence of errors and thus preventable deaths, but all deaths are not preventable. New guidelines for sepsis management and management of undifferentiated clinical presentations are being introduced and we intend to audit the implications of new guidelines.