M.S.

Thesis (MScEng)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: Bioprosthetic heart valves (BHVs) for transcatheter aortic valve implantation (TAVI) have been rapidly developing over the last decade since the first valve replacement using the TAVI technique. TAVI is a minimally invasive valve replacement procedure offering lifesaving treatment to patients who are denied open heart surgery. The biomedical engineering research group at Stellenbosch University designed a 19 mm balloon expandable BHV for TAVI in 2007/8 for testing in animal trials. In the current study the valve was enlarged to 23 mm and 26 mm diameters. A finite element analysis was performed to aid in the design of the stents. New stencils were designed and manufactured for the leaflets using Thubrikar‟s equations as a guide. The 23 mm valve was manufactured and successfully implanted into two sheep. Fluid structure interaction (FSI) simulations constitute a large portion of this thesis and are being recognized as an important tool in the design of BHVs. Furthermore, they provide insight into the interaction of the blood with the valve, the leaflet dynamics and valve hemodynamic performance. The complex material properties, pulsating flow, large deformations and coupling of the fluid and the physical structure make this one of the most complicated and difficult research areas within the body. The FSI simulations, of the current valve design, were performed using a commercial programme called MSC.Dytran. A validation study was performed using data collected from a cardiac pulse duplicator. The FSI model was validated using leaflet dynamics visualisation and transvalvular pressure gradient comparison. Further comparison studies were performed to determine the material model to be used and the effect of leaflet free edge length and valve diameter on valve performance. The results from the validation study correlated well, considering the limitations that were experienced. However, further research is required to achieve a thorough validation. The comparative studies indicated that the linear isotropic material model was the most stable material model which could be used to simulate the leaflet behaviour. The free edge length of the leaflet affects the leaflet dynamics but does not greatly hinder its performance. The hemodynamic performance of the valve improves with an increase in diameter and the leaflet dynamics perform well considering the increased surface area and length. Many limitations in the software prevented more accurate material models and flow initiation to be implemented. These limitations significantly restricted the research and confidence in the results. Further investigation regarding the implementation of FSI simulations of a heart valve using the commercial software is recommended. / AFRIKAANSE OPSOMMING: Bio-prostetiese hartkleppe (Bioprosthetic Heart Valves - BHVs) wat gebruik word vir transkateter aortaklep-inplantings (Transcatheter Aortic Valve Implantation - TAVI) het geweldig vinnige ontwikkeling getoon in die afgelope tien jaar sedert die eerste klepvervanging wat van die TAVI prosedure gebruik gemaak het. TAVI is ʼn minimaal indringende klepvervangingsprosedure wat lewensreddende behandeling bied aan pasiënte wat ope-hart sjirurgie geweier word. Die Biomediese Ingenieurswese Navorsingsgroep (BERG) by Stellenbosch Universiteit het in 2007/8 ʼn 19 mm ballon-uitsetbare BHV vir TAVI ontwerp vir eksperimente met diere, en hierdie tesis volg op die vorige projekte. In die huidige studie is die klep vergroot na 23 mm en 26 mm in deursnee. ʼn Eindige element analise is gedoen om by te dra tot die ontwerp van die rekspalke vir die klep. Nuwe stensils is ontwerp en vervaardig vir die klepsuile, deur gebruik te maak van Thubrikar se vergelykings. Die 23 mm klep is vervaardig en suksesvol in twee skape ingeplant. Vloeistruktuur interaksie (Fluid Structure Interaction (FSI)) simulasies vorm ‟n groot deel van die tesis en word gesien as ʼn noodsaaklike hulpmiddel in die ontwerp van BHVs. Die simulasies verskaf ook insig in die interaksie van die bloed met die klep, die klepsuil-dinamika en die klep se hemodinamiese werkverrigting. Die komplekse materiaal eienskappe, polsende vloei, grootskaalse vervorming, die verbinding van die vloeistof en die fisiese struktuur maak van hierdie een van die mees gekompliseerde voorwerpe om te simuleer. Die FSI simulasies van die huidige ontwerp, is uitgevoer deur van kommersiële sagteware, MSC.Dytran, gebruik te maak. ʼn Geldigheidstudie wat data gebruik het vanaf die hartklop-nabootser, is uitgevoer. Die FSI model word geverifieer deur klepsuil dinamika visualisering en ʼn vergelyking van die drukgradiënt gebruik te maak. Verdere vergelykende studies is uitgevoer om te bepaal watter materiaal model om te gebruik, asook die uitwerking van die klepsuil-vrye rand en klepdeursnee op die klep se werkverrigting. Die resultate van die studie korreleer goed, in ag genome die beperkings wat ervaar is. Verdere navorsing is egter nodig vir ʼn volledige geldigheidstudie. Vergelykende studies het getoon dat die liniêre isotropiese materiaalmodel die meer stabiele materiaalmodel is wat kan gebruik word om klepsuilgedrag te simuleer. Die vrye-rand lengte van die klepsuil affekteer die dinamika van die klepsuil, maar belemmer nie die werkverrigting grootliks nie. Die hemodinamiese werkverrigting van die klep verbeter met die toename in deursnee en die klepsuil-dinamika vertoon goed in ag genome die verhoogde oppervlak area en lengte. Die vele beperkings in die sagteware het die implementering van meer akkurate materiaalmodelle verhoed. Hierdie beperkings het ʼn verminderde vertroue in die resultate tot gevolg gehad. Verdere ondersoek rakende die implementering van die FSI simulasies van ʼn hartklep deur kommersieel beskikbare sagteware te gebruik, word aanbevel.

This thesis is focused on the nursing care for patient after valvular defects surgery. The aim of this final paper is to ascertain the principles of specialized nursing care for patient after valvular defects surgery, analyse the condition of written standards for providing aftercare to patients who underwent valvular defects surgery, or the state of the nursing protocols in specialized nursing care. The purpose of qualitative - observational research in providing specialized nursing care is to find an answer to the question of whether the specifics of nursing care in Prague cardiac centres are significantly different. The theoretical section contains chapters describing cardiac centres, the history of surgical treatment of heart valves, and the most common valvular heart defects in adulthood. In the theoretical section of this study, I focus in detail on the nursing care for patients following cardiac procedure, ensuring not to forget the monitoring of physiological functions, artificial pulmonary ventilation, and immediate position after elective cardiac surgery. The empirical section is divided into quantitative and qualitative research. The quantitative empirical investigation is focused on an anonymous questionary survey that has been applied in three Prague cardiac centres. Approximately 150...

Beim Tissue Engineering werden Erkenntnisse aus der Medizin, Biologie und Chemie mit Methoden der Ingenieurwissenschaften kombiniert, um biologische Ersatzgewebe herzustellen. Das Konzept besteht darin, aus körpereigenen Zellen einen vitalen und funktionalen Gewebeersatz zu fertigen. Hierbei werden körpereigene Zellen auf ein resorbierbares Gerüst transplantiert, in vitro zu einer stabilen Struktur gefestigt, um letztendlich ein vitales Ersatzgewebe implantieren zu können. Die Konstrukte für die menschliche Herzchirurgie sollten in das umgebende Gewebe einwachsen und haben das Potential sich wie gesundes Gewebe zu entwickeln und mitzuwachsen. / Tissue engineering combines knowledge from the fields of medicine, biology and chemistry with the methods of engineering to create artificial tissue. The concept is to produce vital and functional tissue from endogenous cells. These are seeded on to an absorbable scaffold and consolidated to form a stable structure in vitro, with the aim of eventually being able to produce substitute tissue for implantation. The constructs for human cardiac surgery need to embed into the surrounding tissue and, just like natural tissue, to have the potential to grow and develop.

Durante a triagem do pericárdio bovino, utilizado em válvulas cardíacas artificiais, procura-se determinar a direção das fibras de colágeno e identificar regiões mais homogêneas. Estas características influenciam o comportamento mecânico e a durabilidade destas válvulas. Neste contexto, a tomografia de impedância elétrica (TIE) poderia ser utilizada como ferramenta para avaliar o pericárdio, a partir da estimação da direção média das fibras e da identificação das regiões mais homogêneas. O objetivo deste trabalho é investigar a possibilidade de utilização da técnica de TIE para análise e seleção de pericárdios, melhorando os critérios de seleção deste tecido. Com este propósito, foi desenvolvido um reservatório, para acondicionamento do pericárdio e coleta de dados, e implementado um algoritmo de Gauss-Newton para estimar a distribuição de resistividade no tecido. Para regularização do problema inverso mal-posto foi desenvolvido e utilizado um prior baseado em amostras. E para avaliar o desempenho do reservatório e do algoritmo de imagem, fantomas e testes in vitro foram realizados. Detectou-se um furo de 2.0 mm de raio provocado no tecido. Portanto, os experimentos mostraram que é possível detectar imperfeições no pericárdio utilizando a técnica de TIE. No entanto, a necessidade de aperfeiçoamento dos eletrodos, fonte de corrente, reservatório e algoritmo (malhas e priors) esta clara se o objetivo final for a seleção de pericárdios para válvulas cardíaca artificiais. / During the selection of bovine pericardium for use in artificial heart valves, one of the goals is to determine the direction of the collagen fibers and to identify more homogeneous regions. These characteristics influence the mechanical behavior and the durability of these valves. In this context, the electrical impedance tomography (EIT) could be employed as a tool to evaluate the pericardium, from the estimation of the mean fiber direction and the identification of homogeneous regions. The objective of this work is to investigate the possibility of using EIT technique for analysis and selection of pericardium, improving the selection criteria of this tissue. With this purpose in mind, it was developed a test bench, to accommodate the pericardium and to collect data, and it was implemented a Gauss-Newton based algorithm to estimate the resistivity distribution map of this tissue. For regularizing this ill-posed problem, it was developed and applied a priormodels sample-based. And for quality evaluation of the test bench and of the image algorithm, phantom experiments and in vitro tests were performed. It was detected a hole of 2.0 mm radius at the tissue. Therefore, the experiments showed that it is possible to detect defects on pericardium using EIT technique. However, the need of improvements on electrodes, current source, test bench and algorithm (meshes and priors) is clear if the final aim is the selection of pericardium for artificial heart valves.

The aortic valve maintains unidirectional blood flow between the left ventricle and the systemic circulation. When diseased, the valve is replaced either by a mechanical or a bioprosthetic heart valve, that carry issues such as thrombogenesis, long term structural failure, and calcification, necessitating the development of more structurally and biologically sufficient long-term replacements. Tissue engineering provides a possible avenue for development, combining cells, scaffolds, and biochemical factors to regenerate tissue. The overall goal of this dissertation was to create a foundation for the rational design of a tissue engineered aortic valve. The novel approach taken in this thesis research was to view each of the three leaflets as a laminate structure. The first three aims consider the leaflet as a laminate structure comprising of layers of collagen, elastin, and glycosaminoglycans (GAGs). In the first aim, the effect of GAGs on the tensile properties and stress relaxation in the leaflet was investigated, by removing GAGs through increasing amounts of hyaluronidase. A decrease in GAGs led to significantly higher elastic moduli, maximum stresses, and hysteresis in the leaflet. In the second aim, the 3D elastic fiber network of the leaflet was characterized using immunohistochemistry and scanning electron microscopy. This structure was found to have regionally varying thicknesses and patterns. In the third aim, a novel hydrogel-fiber composite design was proposed to match the anisotropy of the leaflet. This composite composed of aligned electrospun poly(ε-caprolactone) (PCL) within a poly(ethylene glycol) diacrylate (PEGDA) matrix. Surface modification and embedding of the PCL did not significantly alter the anisotropy or strength of the underlying PCL scaffold, providing the basis for an anisotropic, biocompatible scaffold. In the last aim, a novel co-culture model was designed using magnetic levitation as a layered structure of valvular endothelial cells and interstitial cells. This technique was used to create co-culture models within hours, while maintaining cell phenotype and function, and inducing extracellular matrix formation, as shown by immunohistochemical stains and their gene expression profiling. The overall result of this dissertation is a clearer understanding of the layered structure-function relationship of the aortic valve, and its application towards heart valve tissue engineering.

Native heart valves with limited functionality are commonly replaced by a bileaflet mechanical heart valve (BMHV). However, despite their widespread use, BMHVs still cause major complications, including hemolysis, platelet activation, and thromboembolic events. These complications are believed to be due to the non-physiologic hemodynamic stresses imposed on blood elements by the hinge flows. Three-dimensional characterization of the hinge flows is therefore crucial to ultimately design BMHVs with lower complication rates. This study aims at simulating the pulsatile 3D hinge flows of various BMHVs placed and estimating the thromboembolic potential associated with each hinge. The hinge and leaflet geometries of clinical BMHVs are reconstructed from micro-computed tomography scans. Simulations are conducted using a Cartesian sharp-interface immersed-boundary methodology combined with a second-order accurate fractional-step method. Physiologic flow boundary conditions and leaflet motion are extracted from the Fluid-Structure-Interaction simulations of the BMHV bulk flow. The accuracy of the solver is assessed by comparing the results with experimental data. The numerical results are analyzed using a particle tracking approach coupled with existing blood damage models to relate the flow structures to the risk for blood damage. Calculations reveal complex, unsteady, and highly 3D flow fields. Zones of flow stagnation and recirculation, favorable to thrombosis and regions of elevated shear stresses, which may induce platelet activation, are identified throughout the hinge and cardiac cycle. The hinge gap width and, more importantly, the shape of the hinge recess and leaflet are found to impact the flow distribution. Avoiding sharp corners or sudden shape transitions appear as key geometrical design parameters to minimize flow disturbances and thromboembolic potential. The computed flows underscore the need to perform full 3D pulsatile simulations throughout the cardiac cycle to fully capture the complexity and unsteadiness of the hinge flows. Though based only on three different designs, this study provides general guidelines to optimize the hinge design based on hemodynamic performance and thromboembolic potential. The developed framework enables rapid and cost-efficient pre-clinical evaluation of prototype BMHV designs prior to valve manufacturing. Application to a wide range of hinges with varying design parameters will eventually help in determining the optimal hinge design.

Durante a triagem do pericárdio bovino, utilizado em válvulas cardíacas artificiais, procura-se determinar a direção das fibras de colágeno e identificar regiões mais homogêneas. Estas características influenciam o comportamento mecânico e a durabilidade destas válvulas. Neste contexto, a tomografia de impedância elétrica (TIE) poderia ser utilizada como ferramenta para avaliar o pericárdio, a partir da estimação da direção média das fibras e da identificação das regiões mais homogêneas. O objetivo deste trabalho é investigar a possibilidade de utilização da técnica de TIE para análise e seleção de pericárdios, melhorando os critérios de seleção deste tecido. Com este propósito, foi desenvolvido um reservatório, para acondicionamento do pericárdio e coleta de dados, e implementado um algoritmo de Gauss-Newton para estimar a distribuição de resistividade no tecido. Para regularização do problema inverso mal-posto foi desenvolvido e utilizado um prior baseado em amostras. E para avaliar o desempenho do reservatório e do algoritmo de imagem, fantomas e testes in vitro foram realizados. Detectou-se um furo de 2.0 mm de raio provocado no tecido. Portanto, os experimentos mostraram que é possível detectar imperfeições no pericárdio utilizando a técnica de TIE. No entanto, a necessidade de aperfeiçoamento dos eletrodos, fonte de corrente, reservatório e algoritmo (malhas e priors) esta clara se o objetivo final for a seleção de pericárdios para válvulas cardíaca artificiais. / During the selection of bovine pericardium for use in artificial heart valves, one of the goals is to determine the direction of the collagen fibers and to identify more homogeneous regions. These characteristics influence the mechanical behavior and the durability of these valves. In this context, the electrical impedance tomography (EIT) could be employed as a tool to evaluate the pericardium, from the estimation of the mean fiber direction and the identification of homogeneous regions. The objective of this work is to investigate the possibility of using EIT technique for analysis and selection of pericardium, improving the selection criteria of this tissue. With this purpose in mind, it was developed a test bench, to accommodate the pericardium and to collect data, and it was implemented a Gauss-Newton based algorithm to estimate the resistivity distribution map of this tissue. For regularizing this ill-posed problem, it was developed and applied a priormodels sample-based. And for quality evaluation of the test bench and of the image algorithm, phantom experiments and in vitro tests were performed. It was detected a hole of 2.0 mm radius at the tissue. Therefore, the experiments showed that it is possible to detect defects on pericardium using EIT technique. However, the need of improvements on electrodes, current source, test bench and algorithm (meshes and priors) is clear if the final aim is the selection of pericardium for artificial heart valves.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Over the past few years, there has been increasing evidence of the effect of the oral health over the general health of individuals, supported by a series of biological and epidemiological studies that show a relation between the mouth and many diseases, including cardiovascular diseases. Structural deficiencies and functional abnormalities of heart valves represent an important cause of cardiovascular morbidity and mortality in Brazil, and a few defects have been recently associated with infectious agents. The aim of this study was to identify cariogenic and periodontopathogenic bacteria in dental plaque, saliva and heart valves, without clinical endocarditis, of patients with heart valve diseases, and correlate these findings with the oral health status of the patients. Oral exams using the DMTF (decayed, missing and filled teeth) and PSR (Periodontal Screening and Recording) indexes to evaluate caries and periodontal disease, respectively, were performed. Samples of supragingival and subgingival dental plaque, saliva and cardiac valves were evaluated, through Real Time Polymerase Chain Reaction, for the presence of DNA of Streptococcus mutans (S. mutans), Prevotella intermedia (P. intermedia), Porphyromonas gingivalis (P. gingivalis) and Treponema denticola (T. denticola). A total of 114 samples were collected from 42 patients with a mean age of 55.6  13.8 years. The average number of missing teeth due to caries was 23.52  9.41 teeth per patient, and according to the highest score of periodontal disease observed for each patient, excluding edentulous patients (44.0%), periodontal pockets over 4mm (43.4%) and dental calculus (34.7%) were detected in a higher number of patients. The molecular analysis of the oral samples revealed high frequency of S. mutans and P. intermedia in supragingival dental plaques, subgingival dental plaques and saliva of dentate and edentulous patients (variation 60.0% - 100.0%), while P. gingivalis and T. denticola were detected in a smaller number of oral samples (variation 17.6% - 64.0%). The microorganism most frequently detected in heart valve samples was the S. mutans (89.3%), followed by P. intermedia (19.1%), P. gingivalis (4.2%) e T. denticola (2.1%). Significant difference was observed between the frequency of P. intermedia, P. gingivalis and T. denticola in the heart valve and dental plaque, as oposed to S. mutans. The identification of oral bacteria, especially S. mutans, in heart valves of patients with a previous history of dental caries and gingivitis/periodontitis suggests the possible involvement of these pathogens in the etiopathogenesis of heart valve diseases. / Atualmente, cada vez mais se tem evidÃncias do efeito da condiÃÃo oral na saÃde geral dos indivÃduos, atravÃs de uma sÃrie de estudos epidemiolÃgicos e biolÃgicos que mostram uma relaÃÃo entre a boca e diversas doenÃas, incluindo as doenÃas cardiovasculares. Desordens estruturais e nas funÃÃes das vÃlvulas cardÃacas representam uma importante causa de morbidade e mortalidade cardiovascular no Brasil, sendo alguns processos, como a estenose aÃrtica degenerativa, mais recentemente associados a agentes infecciosos. O objetivo desta pesquisa foi identificar bactÃrias cariogÃnicas e periodontopatogÃnicas na placa dental, saliva e vÃlvulas cardÃacas, sem endocardite clÃnica, de pacientes com doenÃa valvar, correlacionando esses achados à condiÃÃo bucal dos indivÃduos. AvaliaÃÃo, quanto Ãs doenÃas cÃrie e periodontal, foi realizada, atravÃs dos Ãndices CPO-D (Dentes Permanentes Cariados, Perdidos e Obturados) e PSR (Registro Periodontal Simplificado), respectivamente. Amostras de placa dental supragengival, subgengival, saliva e vÃlvula cardÃaca foram coletadas para investigaÃÃo da presenÃa de DNA, atravÃs de PCR (ReaÃÃo em Cadeia de Polimerase) em tempo real, de Streptococcus mutans (S. mutans), Prevotella intermedia (P. intermedia), Porphyromonas gingivalis (P. gingivalis) e Treponema denticola (T. denticola). Um total de 114 amostras foi coletado de 42 pacientes com mÃdia de idade de 55.6  13.8 anos. A mÃdia de dentes perdidos devido à cÃrie, por paciente, foi em torno de 23.52  9.41 e, segundo o maior grau de doenÃa periodontal observado no indivÃduo, excluindo-se os pacientes desdentados totais (44.0%), bolsa superior a 4 mm (43.4%) e o cÃlculo dental (34.7%) esteve presente em um maior nÃmero de pacientes. A anÃlise molecular das amostras bucais revelou alta frequÃncia de S. mutans e P. intermedia nas placas supragengival, subgengival e saliva de pacientes dentados e desdentados (variando entre 60.0% e 100.0%), enquanto que P. gingivalis e T. denticola estiveram presentes em menor nÃmero de amostras bucais (variando entre 17.6% e 64.0%). O micro-organismo mais frequentemente encontrado nas amostras valvares foi o S. mutans (89.3%), seguido da P. intermedia (19.1%), P. gingivalis (4.2%) e T. denticola (2.1%). DiferenÃa significativa foi encontrada entre a presenÃa de P. intermedia, P. gingivalis e T. denticola na vÃlvula e na placa dental, diferentemente do S. mutans. A identificaÃÃo de bactÃrias orais, principalmente S. mutans, em vÃlvulas cardÃacas de pacientes com elevada experiÃncia prÃvia de cÃrie e ocorrÃncia de gengivite/periodontite, sugere o possÃvel envolvimento desses patÃgenos nas doenÃas valvares.

The thesis deals with CFD solution of flow through mechanical heart valves. The opening part includes a research on the negative impacts of implantation of artificial heart valves and the common approaches used in their modeling. This is followed by a detailed analysis of the dynamic mesh functionality and CFD solution is performed using the open-source library FOAM-extend. Part of the thesis focuses on evaluation of the geometry modifications from the perspective of forming the instabilities of the current and the course of force effects on the valve.