Materials which exhibit non-linear mechanical behaviors under large deformations are generally classified as “soft matter”. Elastomers represent an important class of soft materials which have wide commercial applications and isotropic non-linear behavior. In contrast, biological materials have anisotropic responses due to their heterogeneous and composite architectures. The underlying microstructure determines the arterial macroscopic behavior and is represented through constitutive models to describe the stress-strain relationships. Mechanical characterization and development of constitutive models that describe these non-linear and anisotropic properties are essential to our understanding of the structure-property relationships in these materials. In this study, we use two model systems to link the local microstructure to the overall macroscopic behaviors of soft matter. First, we delineate the roles of individual network topological factors in determining the overall macroscopic behavior of isotropic silicone elastomers using specimens fabricated with differential amounts of crosslinking. We performed mechanical experiments, within a theoretically motivated continuum mechanical framework, using a custom made planar biaxial testing instrument. These experiments demonstrate the contributions of physical entanglements and chemical crosslinks to the overall mechanical properties of silicone elastomers. Further, we show that the slip-link form of strain energy function is better suited to describe the material properties in the low to moderate regions of the stress-strain behavior. However, this model does not predict the stiffening response of elastomers at higher deformations, which is better captured using the Arruda-Boyce form of strain energy function. To explore the effects of individual topological factors on the overall network properties, we performed swelling experiments of silicone specimens in xylene and quantified variations in the polymer-solvent interaction parameter, χ, given by the Frenkel-Flory-Rehner (FFR) model. Further, we characterized the viscoelastic properties using dynamic mechanical analysis. Our results show that χ is not a constant, as assumed in the FFR model, but bears a linear relation to the equilibrium polymer volume fraction. To characterize the contribution of trapped entanglements to the overall mechanical behaviors, we use scaling laws in polymer physics and investigate the dependence of equilibrium volume fraction and experimentally obtained elastic moduli. Further, dynamic mechanical analysis demonstrated an increase in complex modulus with increase in the cross linking density. Finally, we examined variations in the uniaxial and the dynamical mechanical properties of silicone elastomers with storage time. Our results show that the time dependent increase in the modulus correlated with the formation of slip-links in the samples aged for a significantly long time in air. Together, these comprehensive studies show the importance of individual network features which affect the overall macroscopic properties of elastomers. Second, we use a multilayered and composite arterial model system to explore the passive material properties of arteries due to anisotropic layouts of extracellular matrix proteins, collagen and elastin. We characterized the mechanical properties of diseased human ascending thoracic aortic dissected (TAD) tissues, obtained from consenting patients undergoing emergency surgical repair to replace the diseased region, using multiple biaxial tests. We fit these results to micro structurally motivated Holzapfel-Gasser-Ogden model which is frequently used in the arterial mechanics literature. Our results show a higher stiffness for TAD tissues as compared to control aorta, without the presence of atherosclerotic plaques or other arterial disease. To study the directional variation in the mechanical properties of TAD tissues, we compared the stiffness in circumferential longitudinal directions at high and low stress region of equibiaxial experimental data. We observed no differences in the stiffness of TAD tissues in the circumferential and longitudinal directions. Further, we do not see any directional variations in the ultimate tensile stress, maximum extensibility, and modulus calculated in the low stretch region of uniaxial stress-strain response in TAD tissues. Histological analysis of TAD tissues showed a decrease in elastin content and an increase in collagen content as compared to control tissues. Higher TAD tissue stiffness also correlated with reduced elastin content in the arterial walls. To investigate the strain rate dependence of measured mechanical properties we use high testing rates of 1mm/sec to show that the TAD tissues have higher stiffness in the circumferential direction as compared to longitudinal direction. Finally, we used peel experiments to quantify the rupture potential of aortic dissected tissues. Our results show that TAD tissues have reduced delamination strength between layers as compared to control aortic tissues. To the best of our knowledge, no previous study has reported the mechanical property of human TAD tissues and these are the only biomechanical results on TAD tissues reported in specimens from South Asian patients. We hope that such studies will be useful for researchers who rely on microstructure based constitutive models to accurately describe the mechanical environment of cells which are important in the remodeling of tissues and in numerical models to assess mechanical criteria which may lead to the growth or dissection of arterial tissues.

The aim of this study is to analyse a genetic and proteomic aspects that could play an important role in development of chosen cardiovascular disease. Matrix metalloproteinases are enzymes that contribute strongly to the degradation of extracellular matrix components. In this study the serological levels of MMP-2 and MMP-9 were investigated using immunological testing in patients with aortic valve disease and in patients with myocardial infarction. Significantly higher levels of MMP-2 and MMP-9 were determined in both above mentioned groups of patients. Association of serum levels of MMP-2 and MMP-9 and development of concomitant aortic dilatation was not confirmed in patients with aortic valve disease. Changes in serum levels within 24 hours and after 6 months post myocardial infarction were characterized. About 10 % of patients operated for aortic valve disease suffer simultaneously from ascending aortic dilatation. The current study did not reveal any significant genetic variation in TGFBR2 gene and in chosen exons of FBN1 gene in these patients. Further genetic research is needed to identify the cause of the pathology in aortic wall. Gene expression of selected genes was measured by microarray screening in patients with myocardial infarction. These genes were related to MMPs and did not show...

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[pt] Doenças cardiovasculares são responsáveis por um elevado número de óbitos em seres humanos. Muitas dessas patologias são dependentes do ciclo cardíaco e estão localizadas na aorta, a maior e principal artéria do nosso corpo. O conhecimento dos padrões de escoamento e distribuições de tensões nas paredes da aorta podem auxiliar no diagnóstico e prevenção de algumas dessas doenças. Dessa forma, estudou-se numericamente o escoamento do sangue, durante o ciclo cardíaco, em um modelo 3D da aorta de um paciente específico, após a implantação de TAVI (Transcatheter Aortic Valve Implantation). O ciclo cardíaco é formado por dois períodos chamados de sístole e diástole. Durante a sístole, sangue é bombeado do coração para a aorta, apresentado altos valores de vazão, resultando em escoamento turbulento. Por outro lado, na diástole, com o fechamento da válvula aórtica, o sangue escoa com baixas velocidades em regime laminar. Até hoje, cientistas enfrentam um desafio na modelagem da turbulência, pois não existe uma única modelagem que forneça previsibilidade para todas as situações envolvendo o regime turbulento, com esforço computacional razoável. Para seleção do modelo de turbulência mais adequado para análise do escoamento no interior da aorta, na presença da transição de regimes de escoamento durante o ciclo cardíaco, com um custo razoável, selecionou-se a metodologia baseada na Média de Reynolds. Diferentes modelos foram comparados com dados experimentais extraídos do mesmo modelo aórtico em escala real, porém em regime permanente, com vazão correspondente ao pico da sístole. Por fim, avaliou-se o impacto das condições de contorno e dos modelos de turbulência durante o ciclo cardíaco na distribuição e valores de tensões e grandezas turbulentas no endotélio vascular. Mostrou-se que a distribuição espacial das médias temporais de tensão foram qualitativamente e quantitativamente similares, para os dois ciclos cardíacos representativos de diferentes pacientes, porém com pequenas mudanças locais para cada caso. Em termos dos modelos de turbulência, observou-se que o modelo SAS (Scale Adaptive Simulation) foi capaz de representar a relaminarização do escoamento sanguíneo no período diastólico. / [en] Cardiovascular diseases are responsible for a high number of deaths in humans. Many of these pathologies are dependent on the cardiac cycle and are located in the aorta, the largest and main artery in our body. Knowledge of flow patterns and stress distributions in the walls of the aorta can help in the diagnosis and prevention of some of these diseases. Thus, the flow of blood during the cardiac cycle was numerically studied in a 3D model of the aorta of a specific patient, after TAVI (Transcatheter Aortic Valve Implantation) implantation. The cardiac cycle consists of two periods called systole and diastole. During the systole, blood is pumped from the heart to the aorta, presenting high flow rates, resulting in a turbulent flow. On the other hand, in diastole, with the closure of the aortic valve, the blood flows with low velocities in laminar regime. Until today, scientists face a challenge in turbulence modeling, as there is no single model that provides predictability for all situations involving the turbulent regime, with reasonable computational effort. In order to select the most suitable turbulence model for the analysis of the flow inside the aorta, in the presence of the transition of flow regimes during the cardiac cycle, with a reasonable cost, the methodology based on the Reynolds Average was selected. Different models were compared with experimental data extracted from the same real-scale aortic model, but a in steady state, with flow corresponding to the systolic peak. Finally, the impact of boundary conditions and turbulence models during the cardiac cycle on the distribution and values of stresses and turbulent quantities in the vascular endothelium were evaluated. It was shown that the spatial distribution of the temporal averages of tension was qualitatively and quantitatively similar, for the two cardiac cycles representative of different patients, but with small local changes for each case. In terms of turbulence models, it was observed that the SAS (Scale Adaptive Simulation) model was able to represent the relaminarization of blood flow in the diastolic period.

Die bikuspide Aortenklappe gilt als Risikofaktor für das frühzeitige und häufige Auftreten von Aortenklappenvitien, Aneurysmen und Dissektionen. Das Ziel dieser Arbeit ist es, ein begründetes chirurgisches Therapiekonzept für Patienten mit bikuspider Aortenklappe und Dilatation der Aorta ascendens zu entwickeln. Wir analysierten die Daten von 555 Patienten mit bikuspider und 2015 Patienten mit trikuspider Aortenklappe, die sich in unserer Einrichtung einer Operation an der Aortenklappe und/ oder einem Eingriff im Bereich der Aorta ascendens unterzogen. Die Aorta ascendens wurde angiographisch, echokardiographisch und mittels CT auf ihre Konfiguration analysiert und histologisch und histomorphometrisch beschrieben. Auch wurden die Langzeitergebnisse nach Aorta ascendens Reduktionsplastik erfasst. Bei Patienten mit bikuspider Aortenklappe sind mit zunehmendem Durchmesser der Aorta ascendens häufiger die histologischen Zeichen einer Dilatation zu finden. Schwerere strukturelle Veränderungen, insbesondere eine höhergradige zystische Medianekrose, sind nicht zu beobachten. Die Aorta Ascendens Reduktionsplastik zeigt bei Patienten mit bikuspider Aortenklappe und Dilatation der Aorta ascendens gute Langzeitergebnisse. Nur bei Patienten mit nicht optimaler Durchmesser-Reduktion bei der Operation kommt es zu einer späteren Redilatation. / The bicuspid aortic valve is a known risk factor for the early and frequent occurrence of aortic valve defects, aneurysms and dissections. This study aims to develop an appropriate surgical therapy concept for patients with bicuspid aortic valve and dilatation of the ascending aorta. The data of 555 patients with bicuspid and 2015 patients with tricuspid aortic valve who underwent surgical treatment of the aortic valve and/or of the ascending aorta at our institution were evaluated. We analyzed the configuration of the ascending aorta by angiography, echocardiography and CT and described the aortic wall by histological and histomorphometric examination. We also analyzed the long-term results after reduction aortoplasty of the ascending aorta. Histological examination of the aortic wall specimens showed that patients with bicuspid aortic valve with increased diameter of the ascending aorta more often have histological signs of dilatation. More severe histological changes such as cystic media necrosis did not occur. Reduction aortoplasty of the ascending aorta shows good long-term results in patients with bicuspid aortic valve and dilatation of the ascending aorta. Only in patients in whom surgical reduction is less than optimal does redilatation occur later.

In the first part of this dissertation, the phenomenon of self-sustained pressure os-cillations due to the flow past a circular, axisymmetric cavity, associated with inline gate valves, was investigated. In many engineering applications, such as flows through open gate valves, there exists potential for coupling between the vortex shedding from the up-stream edge of the cavity and a diametral mode of the acoustic pressure fluctuations. The effects of the internal pipe geometry immediately upstream and downstream of the shal-low cavity on the characteristics of partially trapped diametral acoustic modes were in-vestigated numerically and experimentally on a scaled model of a gate valve mounted in a pipeline that contained convergence-divergence sections in the vicinity of the valve. The resonant response of the system corresponded to the second acoustic diametral mode of the cavity. Excitation of the dominant acoustic mode was accompanied by pressure oscillations, and, in addition to that, as the angle of the converging-diverging section of the main pipeline in the vicinity of the cavity increased, the trapped behavior of the acoustic diametral modes diminished, and additional antinodes of the acoustic pressure wave were observed in the main pipeline. In addition to that, the effect of shallow chamfers, introduced at the upstream and/or downstream cavity edges, was investigated in the experimental system that con-tained a deep, circular, axisymmetric cavity. Through the measurements of unsteady pressure and associated acoustic mode shapes, which were calculated numerically for several representative cases of the internal cavity geometry, it was possible to identify the configuration that corresponded to the most efficient noise suppression. This arrangement also allowed calculation of the azimuthal orientation of the acoustic modes, which were classified as stationary, partially spinning or spinning. Introduction of shallow chamfers at the upstream and the downstream edges of the cavity resulted in changes of azimuthal orientation and spinning behaviour of the acoustic modes. In addition, introduction of splitter plates in the cavity led to pronounced change in the spatial orientation and the spinning behaviour of the acoustic modes. The short splitter plates changed the behaviour of the dominant acoustic modes from partially spinning to stationary, while the long split-ter plates enforced the stationary behaviour across all resonant acoustic modes. Finally, the evolution of fully turbulent, acoustically coupled shear layers that form across deep, axisymmetric cavities and the effects of geometric modifications of the cavity edges on the separated flow structure were investigated using digital particle image velocimetry (PIV). Instantaneous, time- and phase-averaged patterns of vorticity pro-vided insight into the flow physics during flow tone generation and noise suppression by the geometric modifications. In particular, the first mode of the shear layer oscillations was significantly affected by shallow chamfers located at the upstream and, to a lesser degree, the downstream edges of the cavity. In the second part of the dissertation, the performance of aortic heart valve pros-thesis was assessed in geometries of the aortic root associated with certain types of valve diseases, such as aortic valve stenosis and aortic valve insufficiency. The control case that corresponds to the aortic root of a patient without valve disease was used as a reference. By varying the aortic root geometry, it was possible to investigate corresponding changes in the levels of Reynolds shear stress and establish the possibility of platelet activation and, as a result of that, the formation of blood clots. / Graduate / 0541 / 0546 / 0548 / 0986 / alexbn024@gmail.com

In the first part of this dissertation, the phenomenon of self-sustained pressure os-cillations due to the flow past a circular, axisymmetric cavity, associated with inline gate valves, was investigated. In many engineering applications, such as flows through open gate valves, there exists potential for coupling between the vortex shedding from the up-stream edge of the cavity and a diametral mode of the acoustic pressure fluctuations. The effects of the internal pipe geometry immediately upstream and downstream of the shal-low cavity on the characteristics of partially trapped diametral acoustic modes were in-vestigated numerically and experimentally on a scaled model of a gate valve mounted in a pipeline that contained convergence-divergence sections in the vicinity of the valve. The resonant response of the system corresponded to the second acoustic diametral mode of the cavity. Excitation of the dominant acoustic mode was accompanied by pressure oscillations, and, in addition to that, as the angle of the converging-diverging section of the main pipeline in the vicinity of the cavity increased, the trapped behavior of the acoustic diametral modes diminished, and additional antinodes of the acoustic pressure wave were observed in the main pipeline. In addition to that, the effect of shallow chamfers, introduced at the upstream and/or downstream cavity edges, was investigated in the experimental system that con-tained a deep, circular, axisymmetric cavity. Through the measurements of unsteady pressure and associated acoustic mode shapes, which were calculated numerically for several representative cases of the internal cavity geometry, it was possible to identify the configuration that corresponded to the most efficient noise suppression. This arrangement also allowed calculation of the azimuthal orientation of the acoustic modes, which were classified as stationary, partially spinning or spinning. Introduction of shallow chamfers at the upstream and the downstream edges of the cavity resulted in changes of azimuthal orientation and spinning behaviour of the acoustic modes. In addition, introduction of splitter plates in the cavity led to pronounced change in the spatial orientation and the spinning behaviour of the acoustic modes. The short splitter plates changed the behaviour of the dominant acoustic modes from partially spinning to stationary, while the long split-ter plates enforced the stationary behaviour across all resonant acoustic modes. Finally, the evolution of fully turbulent, acoustically coupled shear layers that form across deep, axisymmetric cavities and the effects of geometric modifications of the cavity edges on the separated flow structure were investigated using digital particle image velocimetry (PIV). Instantaneous, time- and phase-averaged patterns of vorticity pro-vided insight into the flow physics during flow tone generation and noise suppression by the geometric modifications. In particular, the first mode of the shear layer oscillations was significantly affected by shallow chamfers located at the upstream and, to a lesser degree, the downstream edges of the cavity. In the second part of the dissertation, the performance of aortic heart valve pros-thesis was assessed in geometries of the aortic root associated with certain types of valve diseases, such as aortic valve stenosis and aortic valve insufficiency. The control case that corresponds to the aortic root of a patient without valve disease was used as a reference. By varying the aortic root geometry, it was possible to investigate corresponding changes in the levels of Reynolds shear stress and establish the possibility of platelet activation and, as a result of that, the formation of blood clots. / Graduate / 0541 / 0546 / 0548 / 0986 / alexbn024@gmail.com