Thesis (M. S.)--Chemical and Biomolecular Engineering, Georgia Institute of Technology, 2005. / Dr. Athanassios Sambanis, Committee Member ; Dr. Timothy M. Wick, Committee Member ; Dr. Ajit P.Yoganathan, Committee Chair. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (p. 123-133).

O expressivo número de brasileiros que necessitam correção anatômica da estenose valvar aórtica acentuada e que não realizam cirurgia de substituição valvar devido ao risco proibitivo justifica a necessidade de investigação, tanto da efetividade no cenário clínico real quanto dos custos impostos ao Sistema Único de Saúde e aos planos de saúde suplementar brasileiros pela incorporação do implante transcateter de valva aórtica, que tem se demonstrado efetivo mas oneroso, internacionalmente. No primeiro artigo da tese, avaliaram-se os desfechos intra-hospitalares, a sobrevida e o reembolso pela internação hospitalar de 41 pacientes com idade média de 78,7 ± 6,3 anos, estenose valvar aórtica acentuada, com recusa cirúrgica e decisão multidisciplinar por tratamento transcateter entre outubro de 2010 e outubro de 2015. Os sujeitos foram seguidos prospectivamente por um período mediano de 15,2 (4,5 – 25,6) meses e a sobrevida estimada em 1 e 2 anos foi de 73,2% e 64,1%, respectivamente. Identificou-se que hipertensão pulmonar e revascularização miocárdica cirúrgica prévia estavam independentemente associadas à menor sobrevida. O valor mediano reembolsado pelos pacientes atendidos pelo Sistema Único de Saúde foi R$ 108.634,34 (101.051,05 – 127.255,27) e R$ 115.126,77 (94.603,21 – 132.603,01) para aqueles internados por planos de saúde suplementar ou particulares, sendo o respectivo valor mediano reembolsado pela prótese valvar de R$ 82.000,00 (82.000,00 – 95.450,00) e 84.050,00 (75.000,00 – 92.400,00) Em um grupo de 585 procedimentos de troca valvar aórtica cirúrgica em indivíduos com idade ≥ 60 anos, realizados entre janeiro de 2010 e dezembro de 2015 na mesma instituição, a mortalidade intra-hospitalar estava associada à idade e foi de 5,9% naqueles com idade entre 60 e 70 anos, 10,8% entre 70 e 80 anos e de 22,2% ≥ 80 anos. O reembolso mediano foi de R$ 14.035,96 (11.956,11 – 16.644,90) para os internados pelo Sistema único de Saúde e R$ 20.273,97 (15.358.03 – 32.815,49) pelos planos de saúde suplementar ou particulares. No segundo artigo da tese, identificou-se que do total de 819 pacientes consecutivamente incluídos no Registro Brasileiro de Implante de Bioprótese Aórtica por Cateter entre janeiro de 2008 e outubro de 2015, 15 (1,8%) sofreram perfuração do ventrículo esquerdo. Os pacientes que apresentaram perfuração eram mais idosos (85,4 ± 6,3 vs. 81,5 ± 7,3 anos, p=0,038), predominantemente mulheres (80,0% vs. 50,5%, p=0,024), apresentavam maior fração de ejeção (67,3 ± 7,8% vs. 58,6 ± 15,0%, p=0,001), menor massa ventricular esquerda (203,9 ± 47,1g vs. 247,6 ± 78,7g, p=0,039) e menor altura do tronco da coronária esquerda (11,2 ± 5,4mm vs. 14,0 ± 3,3mm, p=0,034). Os preditores independentes de perfuração do ventrículo esquerdo foram idade e fração de ejeção. No terceiro artigo, descreve-se um caso de ablação septal para tratamento de miocardiopatia hipertrófica obstrutiva assimétrica para posterior implante transcateter de valva aórtica, sugerindo que esta seja uma estratégia factível quando da concomitância dessas duas condições Em conclusão, os desfechos do tratamento transcateter da estenose valvar aórtica acentuada em pacientes inoperáveis são compatíveis com aqueles do cenário idealizado dos ensaios clínicos randomizados, apesar de estarem associados a custos maiores que os anteriormente estimados por painéis de especialistas. O tratamento cirúrgico, por sua vez, apresentou mortalidade maior que aquela idealizada ou relatada como usual. A hipercinesia do ventrículo esquerdo pode favorecer o trauma determinado pelo guia metálico, posicionado em seu interior para realização do procedimento, estando a fração de ejeção independentemente associada à chance de perfuração. Ainda, a ablação septal por álcool eletiva, anterior ao implante transcateter da valva aórtica, é uma abordagem factível para pacientes com hipertrofia ventricular esquerda assimétrica obstrutiva associada à estenose valvar aórtica. / The expressive number of Brazilians who require an anatomic correction for severe aortic valve stenosis and who do not undergo valvar replacement surgery due to prohibitive risk justifies the need to investigate both the effectiveness in the real clinical scenario and the costs imposed to the Public Health System and the Supplementary Health System for the incorporation of the transcatheter aortic valve implantation, which has been shown to be effective but onerous, internationally. In the first article of the thesis, the in-hospital outcomes, long-term survival and reimbursement for 41 patients, with a mean age of 78.7 ± 6.3 years, sever aortic valve stenosis, with surgical refusal and multidisciplinary decision for transcatheter treatment, between October 2010 and October 2015 are described. Subjects were prospectively followed for a median period of 15.2 (4.5 - 25.6) months and the estimated survival at 1 and 2 years was 73.2% and 64.1%, respectively. It was identified that pulmonary hypertension and previous coronary artery bypass grafting were independently associated with lower survival. Median reimbursed values by the Public Health System was R$ 108,634.34 (101,051.05 - 127,255.27) and by supplementary health plans was R$ 115,126.77 (94,603.21 - 132,603.01). The respective median values reimbursed for the valve prosthesis was R$ 82,000.00 (82,000.00 - 95,450.00) and 84,050.00 (75,000.00 - 92,400.00) In a group of 585 surgical aortic valve replacement procedures in subjects aged ≥ 60 years, performed between January 2010 and December 2015 in the same institution, in-hospital mortality was associated with age and was 5.9% in those with age between 60 and 70 years, 10.8% between 70 and 80 years and 22.2% in ≥ 80 years. The median reimbursement was R$ 14,035.96 (11,956.11 - 16,644.90) for those hospitalized by the Public Health System and R$ 20,273.97 (15,358.03 - 32,815.49) by supplementary or private health plans. In the second article of the thesis, it was identified that of the total of 819 patients consecutively included in the Brazilian Registry of Aortic Bioprosthesis Implantation by Catheter (RIBAC) between January 2008 and October 2015, 15 (1.8%) suffered perforation of the left ventricle. Patients with perforation were older (85.4 ± 6.3 vs. 81.5 ± 7.3 years, p=0.038), predominantly women (80.0% vs. 50.5%, p=0.024), had a higher ejection fraction (67.3 ± 7.8% vs. 58.6 ± 15.0%, p=0.001), lower left ventricular mass (203.9 ± 47.1g vs. 247.6 ± 78, 7g, p=0.039) and shorter distance between the aortic annulus and the left main coronary artery ostium (11.2 ± 5.4mm vs. 14.0 ± 3.3mm, p=0.034). The independent predictors of left ventricular perforation were age and ejection fraction. In the third article, a case of septal ablation was described for the treatment of asymmetric obstructive hypertrophic cardiomyopathy for posterior transcatheter aortic valve implantation, suggesting that this is a feasible strategy when these two conditions are concomitant In conclusion, the outcomes of transcatheter treatment of severe aortic stenosis in inoperable patients are compatible with those in the ideal scenario of randomized clinical trials, although they are associated with higher costs than previously estimated by expert panels. Surgical treatment, on the other hand, presented higher mortality than that idealized or reported as usual. The left ventricle hyperkinesia may favor the trauma determined by the metallic guide, positioned inside it to perform the procedure, the ejection fraction being independently associated with the chance of perforation. Furthermore, elective alcohol septal ablation, prior to transcatheter aortic valve implantation, is a feasible approach for patients with obstructive asymmetric left ventricular hypertrophy associated with aortic valve stenosis.

O expressivo número de brasileiros que necessitam correção anatômica da estenose valvar aórtica acentuada e que não realizam cirurgia de substituição valvar devido ao risco proibitivo justifica a necessidade de investigação, tanto da efetividade no cenário clínico real quanto dos custos impostos ao Sistema Único de Saúde e aos planos de saúde suplementar brasileiros pela incorporação do implante transcateter de valva aórtica, que tem se demonstrado efetivo mas oneroso, internacionalmente. No primeiro artigo da tese, avaliaram-se os desfechos intra-hospitalares, a sobrevida e o reembolso pela internação hospitalar de 41 pacientes com idade média de 78,7 ± 6,3 anos, estenose valvar aórtica acentuada, com recusa cirúrgica e decisão multidisciplinar por tratamento transcateter entre outubro de 2010 e outubro de 2015. Os sujeitos foram seguidos prospectivamente por um período mediano de 15,2 (4,5 – 25,6) meses e a sobrevida estimada em 1 e 2 anos foi de 73,2% e 64,1%, respectivamente. Identificou-se que hipertensão pulmonar e revascularização miocárdica cirúrgica prévia estavam independentemente associadas à menor sobrevida. O valor mediano reembolsado pelos pacientes atendidos pelo Sistema Único de Saúde foi R$ 108.634,34 (101.051,05 – 127.255,27) e R$ 115.126,77 (94.603,21 – 132.603,01) para aqueles internados por planos de saúde suplementar ou particulares, sendo o respectivo valor mediano reembolsado pela prótese valvar de R$ 82.000,00 (82.000,00 – 95.450,00) e 84.050,00 (75.000,00 – 92.400,00) Em um grupo de 585 procedimentos de troca valvar aórtica cirúrgica em indivíduos com idade ≥ 60 anos, realizados entre janeiro de 2010 e dezembro de 2015 na mesma instituição, a mortalidade intra-hospitalar estava associada à idade e foi de 5,9% naqueles com idade entre 60 e 70 anos, 10,8% entre 70 e 80 anos e de 22,2% ≥ 80 anos. O reembolso mediano foi de R$ 14.035,96 (11.956,11 – 16.644,90) para os internados pelo Sistema único de Saúde e R$ 20.273,97 (15.358.03 – 32.815,49) pelos planos de saúde suplementar ou particulares. No segundo artigo da tese, identificou-se que do total de 819 pacientes consecutivamente incluídos no Registro Brasileiro de Implante de Bioprótese Aórtica por Cateter entre janeiro de 2008 e outubro de 2015, 15 (1,8%) sofreram perfuração do ventrículo esquerdo. Os pacientes que apresentaram perfuração eram mais idosos (85,4 ± 6,3 vs. 81,5 ± 7,3 anos, p=0,038), predominantemente mulheres (80,0% vs. 50,5%, p=0,024), apresentavam maior fração de ejeção (67,3 ± 7,8% vs. 58,6 ± 15,0%, p=0,001), menor massa ventricular esquerda (203,9 ± 47,1g vs. 247,6 ± 78,7g, p=0,039) e menor altura do tronco da coronária esquerda (11,2 ± 5,4mm vs. 14,0 ± 3,3mm, p=0,034). Os preditores independentes de perfuração do ventrículo esquerdo foram idade e fração de ejeção. No terceiro artigo, descreve-se um caso de ablação septal para tratamento de miocardiopatia hipertrófica obstrutiva assimétrica para posterior implante transcateter de valva aórtica, sugerindo que esta seja uma estratégia factível quando da concomitância dessas duas condições Em conclusão, os desfechos do tratamento transcateter da estenose valvar aórtica acentuada em pacientes inoperáveis são compatíveis com aqueles do cenário idealizado dos ensaios clínicos randomizados, apesar de estarem associados a custos maiores que os anteriormente estimados por painéis de especialistas. O tratamento cirúrgico, por sua vez, apresentou mortalidade maior que aquela idealizada ou relatada como usual. A hipercinesia do ventrículo esquerdo pode favorecer o trauma determinado pelo guia metálico, posicionado em seu interior para realização do procedimento, estando a fração de ejeção independentemente associada à chance de perfuração. Ainda, a ablação septal por álcool eletiva, anterior ao implante transcateter da valva aórtica, é uma abordagem factível para pacientes com hipertrofia ventricular esquerda assimétrica obstrutiva associada à estenose valvar aórtica. / The expressive number of Brazilians who require an anatomic correction for severe aortic valve stenosis and who do not undergo valvar replacement surgery due to prohibitive risk justifies the need to investigate both the effectiveness in the real clinical scenario and the costs imposed to the Public Health System and the Supplementary Health System for the incorporation of the transcatheter aortic valve implantation, which has been shown to be effective but onerous, internationally. In the first article of the thesis, the in-hospital outcomes, long-term survival and reimbursement for 41 patients, with a mean age of 78.7 ± 6.3 years, sever aortic valve stenosis, with surgical refusal and multidisciplinary decision for transcatheter treatment, between October 2010 and October 2015 are described. Subjects were prospectively followed for a median period of 15.2 (4.5 - 25.6) months and the estimated survival at 1 and 2 years was 73.2% and 64.1%, respectively. It was identified that pulmonary hypertension and previous coronary artery bypass grafting were independently associated with lower survival. Median reimbursed values by the Public Health System was R$ 108,634.34 (101,051.05 - 127,255.27) and by supplementary health plans was R$ 115,126.77 (94,603.21 - 132,603.01). The respective median values reimbursed for the valve prosthesis was R$ 82,000.00 (82,000.00 - 95,450.00) and 84,050.00 (75,000.00 - 92,400.00) In a group of 585 surgical aortic valve replacement procedures in subjects aged ≥ 60 years, performed between January 2010 and December 2015 in the same institution, in-hospital mortality was associated with age and was 5.9% in those with age between 60 and 70 years, 10.8% between 70 and 80 years and 22.2% in ≥ 80 years. The median reimbursement was R$ 14,035.96 (11,956.11 - 16,644.90) for those hospitalized by the Public Health System and R$ 20,273.97 (15,358.03 - 32,815.49) by supplementary or private health plans. In the second article of the thesis, it was identified that of the total of 819 patients consecutively included in the Brazilian Registry of Aortic Bioprosthesis Implantation by Catheter (RIBAC) between January 2008 and October 2015, 15 (1.8%) suffered perforation of the left ventricle. Patients with perforation were older (85.4 ± 6.3 vs. 81.5 ± 7.3 years, p=0.038), predominantly women (80.0% vs. 50.5%, p=0.024), had a higher ejection fraction (67.3 ± 7.8% vs. 58.6 ± 15.0%, p=0.001), lower left ventricular mass (203.9 ± 47.1g vs. 247.6 ± 78, 7g, p=0.039) and shorter distance between the aortic annulus and the left main coronary artery ostium (11.2 ± 5.4mm vs. 14.0 ± 3.3mm, p=0.034). The independent predictors of left ventricular perforation were age and ejection fraction. In the third article, a case of septal ablation was described for the treatment of asymmetric obstructive hypertrophic cardiomyopathy for posterior transcatheter aortic valve implantation, suggesting that this is a feasible strategy when these two conditions are concomitant In conclusion, the outcomes of transcatheter treatment of severe aortic stenosis in inoperable patients are compatible with those in the ideal scenario of randomized clinical trials, although they are associated with higher costs than previously estimated by expert panels. Surgical treatment, on the other hand, presented higher mortality than that idealized or reported as usual. The left ventricle hyperkinesia may favor the trauma determined by the metallic guide, positioned inside it to perform the procedure, the ejection fraction being independently associated with the chance of perforation. Furthermore, elective alcohol septal ablation, prior to transcatheter aortic valve implantation, is a feasible approach for patients with obstructive asymmetric left ventricular hypertrophy associated with aortic valve stenosis.

MScEng / Thesis (MScEng (Mechanical and Mechatronic Engineering))--University of Stellenbosch, 2009. / In this project the shape and attachment method of tissue leaflets for a percutaneous aortic valve is designed and tested as a first prototype. Bovine and kangaroo pericardium was tested and compared with natural human valve tissue by using the Fung elastic constitutive model for skin. Biaxial tests were conducted to determine the material parameters for each material. The constitutive model was implemented using finite element analysis (FEA) by applying a user-specified subroutine. The FEA implementation was validated by simulating the biaxial tests and comparing it with the experimental data. Concepts for different valve geometries were developed by incorporating valve design and performance parameters, along with stent constraints. Attachment techniques and tools were developed for valve manufacturing. FEA was used to evaluate two concepts. The influence of effects such as different leaflet material, material orientation and abnormal valve dilation on the valve function was investigated. The stress distribution across the valve leaflet was examined to determine the appropriate fibre direction for the leaflet. The simulated attachment forces were compared with suture tearing tests performed on the pericardium to evaluate suture density. In vitro tests were conducted to evaluate the valve function. Satisfactory testing results for the prototype valves were found which indicates the possibility for further development and refinement.

O pericárdio bovino tratado com glutaraldeído (GTA) e armazenado em formaldeído tem sido utilizado para confecção de biopróteses cardíacas ao longo das últimas décadas, já se tendo acumulado grande experiência com seu manuseio. Sabemos, no entanto, que o uso do GTA associadamente à presença de restos celulares existentes em meio às fibras de colágeno e elastina do pericárdio, são fatores indutores de resposta inflamatória e de enucleação de cristais de cálcio, o que compromete a durabilidade da bioprótese in vivo a longo prazo. No presente trabalho, tivemos como objetivo comparar a resistência mecânica do pericárdio decelularizado com o pericárdio convencional, assim como avaliar sua capacidade de induzir resposta inflamatória em modelo experimental com ratos. Para estudar as duas técnicas, dividimos os pericárdios em dois grupos: Grupo I - pericárdio submetido a tratamento convencional com GTA e Grupo II - pericárdio submetido a tratamento de decelularização previamente ao tratamento convencional com GTA. Após o processamento químico dos pericárdios, as amostras do Grupo II foram histologicamente avaliadas para confirmar a eficácia da decelularização. A seguir, analisamos a resistência mecânica nos dois grupos de pericárdio através dos testes de tração e de desnaturação térmica. Em nossa casuística, os dois grupos tiveram desempenho semelhante. A capacidade de induzir resposta inflamatória foi avaliada em estudo experimental em 50 ratos Wistar, machos, com 3 meses de idade, os quais foram submetidos a implante subcutâneo no abdome de fragmentos de pericárdio dos dois grupos. Igualmente, não evidenciamos diferença significativa. Nossa terceira etapa de avaliação consistiu em confeccionar 3 biopróteses (mitral n. 29) com o pericárdio decelularizado e que foram submetidas a avaliação hidrodinâmica juntamente com uma bioprótese convencional de teste. As biopróteses decelularizadas mostraram ter desempenho hidrodinâmico semelhante à prótese de teste e ao padrão de avaliação de próteses já conhecido da Braile Biomédica (S.J.Rio Preto-SP), todas atingindo a marca de 150 milhões de ciclos. A avaliação histológica do pericárdio das próteses ao fim da ciclagem mostrou padrão microscópico habitual, não tendo havido ruptura ou fragmentação anormal induzida por estresse mecânico. Temos como conclusão que a técnica de decelularização mantém a resistência física do pericárdio em comparação àquele convencionalmente preparado, não levando à fragmentação da matriz de colágeno e elastina e nem à perda de sua resistência mecânica tanto estática quanto dinâmica, além de não ter induzido resposta inflamatória diferente daquela habitualmente encontrada no pericárdio convencional / The bovine pericardium treated with glutaraldehyde (GTA) and stored in formaldehyde has been used in the manufacturing of cardiac bioprosthesis through the past decades, and a great knowledge has been acquired in this field. We know however that the use of the GTA and the presence of cell debris among the collagen and elastin fibers are triggers to induce inflammatory response and calcium deposition in the tissue, what compromises the long term durability of bioprosthesis in vivo. In this paper, our objective was to compare the decellularized and the conventional pericardium mechanical resistance and also its capability of inducing inflammatory response in an animal experimental model. In order to study these two techniques, we divided the pericardia into two groups: Group I- pericardia conventionally treated with GTA and Group II - pericardia previously decellularized and then conventionally treated with GTA. At first, after the pericardia chemical treatment, we performed histological analysis of Group II to certify the efficacy of the decellularization process. Afterwards, we analyzed the mechanical resistance in both groups using the stretching and shrinkage tests. In our samples, both groups had the same performance. The capacity of inducing inflammatory response was evaluated in an experimental study with 50 Wistar rats, male, 3 months old, which were operated to receive the pericardia patches of both groups underneath the dermal layer in the abdomen. We also did not find any difference between the groups. The third step of evaluation was to manufacture three decellularized bioprosthesis and one no decellularized one that were submitted to hydrodynamic tests. The decellularized and the test prosthesis showed the same performance and there was also no difference when compared with the known performance of the Braile Biomédica\'s (S.J.R. Preto-SP) bioprosthesis. They all reached 150 million cicles. The histological avaluation of the bioprosthesis showed the usual microscopic pattern, and there was no abnormal rupture or fragmentation caused by mechanical stress. We have therefore reached to the conclusion that the decellularization technique keeps the physical resistance of the pericardium when compared with the conventionally prepared. It does not cause damage or fragmentation of the collagen and elastin fibers and does not lead to loss of the mechanical resistance. And also, there was no difference in both groups regarding to inflammatory response studied in the animal model

Bileaflet mechanical heart valves (BMHVs), though a life-saving tool in treating heart valve disease, are often associated with serious complications, including a high risk of hemolysis, platelet activation, and thromboembolism. One likely cause of this hyper-coagulative state is the nonphysiologic levels of stress experienced by the erythrocytes and platelets flowing through the BMHVs. Research has shown that the combination of shear stress magnitude and exposure time found in the highly transient leakage jet emanating from the b-datum gap during valve closure is sufficient to cause hemolysis and platelet activation. Regions of flow stasis in the valve vicinity may also allow activated platelets to aggregate and form thrombus. This thesis addresses the hypothesis that passive flow control may have the potential to reduce flow-induced thrombogenicity by altering the fluid mechanics of bileaflet mechanical heart valves. To test this hypothesis, a steady model of the regurgitant b-datum line jet was developed and studied. This model served as a test bed for various vortex generator array designs. The fluid mechanics of the b-datum line jet model was investigated with flow visualization and particle image velocimetry. In vitro tests with whole human blood were performed with and without the vortex generators in order to determine how the presence of the passive flow control affected the propensity of the blood to form thrombus. An effort was then made to correlate the fluid mechanics of the jet model with the procoagulant potential results from the blood experiments. The effect of the vortex generators on the fluid mechanics of the valve under physiologic pulsatile conditions was also investigated via flow visualization in the Georgia Tech Left Heart Simulator. By studying a steady model of the regurgitant b-datum line jet, it was found, using an in vitro system with whole human blood, that the presence of vortex generators significantly decreased the blood's propensity for thrombus formation. The potential of applying passive flow control to cardiovascular hardware in order to mitigate the injurious effects of shear-induced platelet activation is thus demonstrated. The investigation into the effect of vortex generators on the fluid mechanics of the b-datum line jet showed that the jet oscillated aperiodically and that the effect of the applied flow control was played out at both the scale of the chamber (large-scale) and on the scale of the vortex generator fins (small-scale). On the large scale, the presence of vortex generators appeared to decrease the magnitude or frequency of jet oscillation, thereby stabilizing the jet. After removing the effect of the large-scale oscillations via phase averaging, the effect of the vortex generators on the small scale was examined. On the small scale, the jet without flow control was found to have higher levels of velocity RMS, particularly on the jet periphery, and higher levels of Reynolds shear stress. It is proposed that the vortex generators effect this change by generating vorticity in the plane of the jet. This vorticity is theorized to stabilize the jet, delaying roll-up of the jet shear layer which occurs via the Kelvin-Helmholtz instability. The method by which the vortex generators acted on the fluid mechanics of the steady jet system to decrease the blood's procoagulant potential was investigated via flow visualization and DPIV. The results from these studies implicate two possible mechanisms by which the vortex generators may act. First, the peak turbulent shear stresses in the jet were reduced by 10-20% with the application of vortex generators. Even if only a few platelets were activated in each passage through the valve, the cumulative effect of this difference in peak stresses after many passes would be greatly magnified. Thus, this reduction in turbulent shear stresses may be sufficient to explain the change seen in the blood's procoagulant potential with the application of passive flow control. It is suspected, though, that the second mechanism is dominant. The flow fields revealed that the presence of the vortex generators delayed or prevented the roll-up of the Kelvin-Helmholtz instability in the b-datum jet's shear layers into discrete vortices. By doing so, it is thought that opportunities for the interaction of activated and unactivated platelets entrained in these vortices were prevented, thereby inhibiting further propagation of the coagulation cascade. Even if the rate at which platelets were activated was similar for cases with and without flow control, it seems that the flow fields experienced by the platelets subsequent to activation can determine the level of procoagulant potential. Under the steady conditions observed in this experiment, the jet influenced by vortex generators was thus shown to induce significantly lower levels of procoagulant potential.

New 3D multi-scale modeling approaches for the structural analysis of native and prosthetic Aortic Valves (AV) are investigated. Three different nonlinear hyperelastic constitutive material models for the mechanical behavior of the AV tissue are introduced. The first is the well-known Holzapfel hyperelastic, anisotropic and homogeneous model. The second model, termed the Collagen Fiber Network (CFN), is a heterogeneous model that recognizes the hyperelastic collagen and elastin layers using different layered finite elements. The third hyperelastic model is implemented using a new nonlinear micromechanical formulation of the High Fidelity Generalized Method of Cells (HFGMC) originally proposed by Aboudi. The latter two material models are heterogeneous and explicitly recognize the in-situ tissue constituents. Initially, a full scale 3D structural model of a polymeric-based prosthetic AV model is studied. This model is verified using deformation metrics obtained from images taken with high speed cameras during in-vitro experiments. The predictions from the proposed polymeric AV model are in good agreement with the test data. Next, the three tissue material models are examined in their ability to predict the anisotropic material behavior of porcine AV leaflet tissue. The Holzapfel model is calibrated from the overall anisotropic uni- and biaxial stress-strain data while the in-situ elastin and collagen constituents in the CFN and HFGMC models are calibrated to match the overall effective responses. Dynamic structural analysis is performed for the porcine AV with applied transvalvular pressure measured from repeated in-vitro tests conducted in this study. Principal stretches are computed from the experimental measurements and compared with the AV material-structural predictions. The proposed multi-scale modeling approach for the native AV is capable of predicting the structural behavior during the entire cardiac cycle without suffering from numerical convergence problems. Finally, new nonlinear micromechanical formulations based on the HFGMC method are developed and applied for various types of tissue materials including the human arterial wall layers and porcine AV leaflets. The proposed hyperelastic HFGMC model is compared to the CFN model and the Holzapfel models. It is shown that the HFGMC is an effective modeling approach for the arteries especially when the collagen fiber network has a periodic microstructure.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2006. / Härtill 6 uppsatser.

Thesis (M.S.)--Mississippi State University. Department of Agricultural and Biological Engineering. / Title from title screen. Includes bibliographical references.