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.

O pericárdio bovino é um tecido biológico utilizado na fabricação de vários produtos para a saúde e também em válvulas cardíacas desde o início da década de setenta, porém, ainda requer estudos mais aprofundados no que diz respeito às mudanças que os tratamentos químicos utilizados para confecção das válvulas ocasionam. Atualmente a engenharia de tecidos estuda a descelularização do pericárdio bovino como um processo para retirar os componentes celulares, mantendo intacta a matriz extracelular (MEC), preservando a integridade do colágeno e também pode atuar como anticalcificante. Porém, é necessário saber qual o impacto que o tratamento químico trará nas propriedades mecânicas do tecido, como tensão máxima, deformação específica e alongamento. Nos trabalhos observados, os testes mecânicos realizados nos pericárdios bovinos descelularizados foram feitos no tecido sem serem submetidos a uma pré-tensão, a qual é necessária na maioria das vezes, para formação das cúspides durante a confecção das válvulas cardíacas ou outro dispositivo médico. Por essa razão, foi realizado um estudo do efeito na propriedade mecânica que uma determinada pressão exerce sobre o pericárdio bovino, que passou pelo processo de descelularização. Em paralelo também foi feito uma avaliação histológica do tecido para verificar a ausência de células e a preservação das fibras de colágeno no tecido descelularizado. Foram preparados quatro grupos diferentes para a realização dos testes. O grupo I chamado de grupo controle. O grupo II, onde os pericárdios foram descelularizados com o método PUC I. O grupo III foi tratado como o grupo I, porém sob pressão de 240 mmHg. Já o grupo IV, os pericárdios foram descelularizados e em seguida submetidos à mesma pressão utilizando solução de glutaraldeído 0,2% e 0,5%. Após os tratamentos dos grupos, todas as amostras foram tingidas em solução de azul de metileno 0,03% para melhor visualização das fibras do tecido. Em seguida os tecidos foram cortados a laser para obtenção dos corpos de prova e submetidos ao ensaio de tração. Obteve-se a partir do ensaio, a tensão máxima das amostras, a deformação específica e o alongamento na ruptura. Foi observado que nos grupos onde foram submetidos à pressão tiveram uma tensão máxima menor do que os grupos sem pressão e um maior alongamento. Verificou-se que o efeito da pressão diminuiu a espessura dos tecidos. O processo de descelularização se mostrou eficaz uma vez que foi demonstrada a ausência de células e a preservação das fibras de colágeno após técnica utilizada. / The pericardium is a biological tissue used in the manufacture of various products for medical advices and manufacture of heart valves since the early seventies, however, it still requires further study with regard to the changes that the chemical treatments used to manufacture the valves cause. Several studies show that the tissue often undergoes a process of calcification generated by mechanical stress of opening and closing of the leaflets, damaging the hydrodynamics making valvular replacement necessary. Currently tissue engineering study decellularization process of the bovine pericardium to remove cellular components while preserving the extracellular the matrix (ECM), preserving the integrity of collagen it and can also act as anti-calcification. However, one must know the impact that chemical treatment will bring on the mechanical properties of the tissue, such as tensile strength, strain and elongation percentage. In examined studies, the mechanical tests performed on bovine pericardium decellularized tissue was made without being subjected to a pre-tension which is necessary in most cases for formation of the leaflets during the manufacturing of heart valves. For this reason, a study of the effect on mechanical property that a certain pressure exerts on the pericardium, which passed the decellularization process was made. In parallel it was also made a histological evaluation of the tissue to verify the absence of cells and preservation of collagen fibers in decellularized tissue. Four different groups were prepared for test. The group I was called a control group. In group II, the pericardia were decellularized with the PUC method I. Group III was treated as group I, but under pressure of 240 mmHg. The group IV, the pericardia were decellularized and then subjected to pressure using glutaraldehyde 0.2% and 0.5%. After treatment of the groups, all samples were stained in a solution of blue methylene 0.03% for better visualization of the fibers of the tissue. Then the tissues were cut by laser to obtain the specimens and subjected to tensile test. It was obtained from the test, the tensile strength of the samples, the strain and elongation percentage at break. It is observed that the groups which underwent pressure had a lower tensile strength than those without pressure and on the other hand showed a greater elongation percentage. Thus, it can be verified that the effect of the pressure decreased the thickness of the tissues. The decellularization process has show efficient since it has demonstrated the absence of cells and preservation of collagen fibers after technique.

Ce travail de doctorat se décompose en quatre parties distinctes. La première partie concerne la caractérisation hémodynamique sur simulateur cardiovasculaire de prothèses valvulaires mitrales de différents constructeurs en vue de leur évaluation clinique et du diagnostique de leur dysfonction. La seconde partie se focalise sur les prothèses valvulaires mécaniques bi-clapet au travers desquels le phénomène de recouvrement de pression dû au passage de l'écoulement à travers les trois orifices formés par les clapets peut engendrer une surestimation du gradient transvalvulaire. Ce phénomène peut entrainer une ambiguïté lors de l'évaluation de la prothèse en cas de gradient transvalvulaire important. Cette partie s'attache à quantifier ce phénomène et à évaluer l'influence d'une dysfonction (disproportion patient-prothèse ou obstruction d'un clapet) sur celui-ci. La troisième partie concerne la procédure valve-in-valve dans laquelle une prothèse percutanée est implantée dans une bioprothèse défaillante. Elle fournit une caractérisation in vitro, première au niveau mondial, d'assemblages de la prothèse SAPIEN Edwards dans des bioprothèses issues de différents constructeurs. Enfin et suite à la mise en évidence dans les parties précédentes de profils de vitesse en amont de la prothèse ne pouvant être assimilés à des profils plats, l'étude des patrons de flux auriculaires a été réalisée grâce à des acquisitions in-vitro. / This PhD work is divided into four different parts. the first part concerns the hemodynamic characterization by in-vitro cardiovascular testing of mitral valvular prosthesis from different manufacturers in order to provide reference values for clinical diagnosis. The second part focus on bi leaflet mechanical heart valve in each pressure recovery resulting of flow through the three orifices could lead to an overestimation of transvalvular pressure gradient. This could create ambigious assessment in case of high value of transvalvular pressure gradient. This part aims to quantify this pressure recovery and identify the influence of dysfunction (leaflet obstruction or patient prosthesis mismatch) on this value. Third part consists in valve-in-valve procedure in which a transcatheter valve is impllanted in a failled bioprosthesis. It provides in vitro testing, first globally, of assemblies composed of SAPIEN Edwards prostheses in different manufacturers' bioprosthesis.As highlighted in the previous parts inflows of the mitral prostheses can not be considered as plane and results of left atrium flow patterns. The last part studies the left atrium flow following mitral valve replacement.

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

Orientador: Domingo Marcolino Braile / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T03:55:43Z (GMT). No. of bitstreams: 1 Antoniali_Fernando_M.pdf: 4775200 bytes, checksum: 8361f227d501574e0c98c3965065c58b (MD5) Previous issue date: 2006 / Resumo: Objetivo: Determinar a proporção existente entre os segmentos do anel da valva tricúspide normal em humanos. Método: Foram estudados 30 corações de cadáveres humanos não formolizados, com menos de 6h de período ¿post-mortem¿, sem lesões congênitas ou adquiridas e com valvas tricúspides sem deformidades e continentes. A continência desta valva foi confirmada por injeção de água sob pressão no interior do ventrículo direito estando a valva pulmonar fechada. Foram realizadas fotos digitais da valva tricúspide com o anel valvar íntegro e após secção na comissura póstero-septal e retificação do anel valvar. Estas fotos contendo escalas milimetradas foram avaliadas por programa específico de computador. Foram feitas medidas computadorizadas do perímetro, segmento septal e segmento ântero-posterior do anel valvar íntegro. Nesta condição também foram feitas medidas da distância linear entre as comissuras ântero-septal e póstero-septal. Na condição de anel valvar retificado, foram realizadas medidas computadorizadas e manuais do perímetro e dos segmentos septal, anterior e posterior do anel valvar tricuspídeo. Compararam-se as medidas médias e as razões entre elas nas condições de anel íntegro e retificado. Compararam-se, também, a forma computadorizada e manual de mensuração do anel. Resultados: Nas medidas computadorizadas realizadas com imagens digitais do anel valvar íntegro, os valores médios do perímetro, segmento septal e ântero-posterior foram 105mm (±12,7), 30,6mm (±3,7) e 74mm (±9,4), respectivamente. A distância linear média entre as comissuras ântero-septal e póstero-septal foi de 28,9mm (±3,4). Nas medidas computadorizadas realizadas com imagens digitais do anel valvar retificado, os valores médios foram 117,5mm (±13,3), 32mm (±3,7), 46,3mm (±8,3) e 39,1mm (±8,5), respectivamente para perímetro, segmento septal, anterior e posterior. A razão média entre o segmento ântero-posterior e o septal foi 2,43 (±0,212) e 2,67 (±0,304) respectivamente em anéis íntegros e retificados. Houve diferenças significantes entre as medidas do perímetro (p<0,0001), do segmento septal (p=0,003) e do segmento ântero-posterior (p<0,0001) quando realizadas em anéis íntegros e retificados. As razões entre segmento ântero-posterior e septal também apresentaram diferença significante (p=0,0005). As medidas manuais do anel valvar retificado apresentaram os valores médios de 118,5mm (±12,7), 32,6mm (±3,4), 46,6mm (±7,7) e 39,3mm (±7,9), respectivamente para perímetro, segmento septal, anterior e posterior. Não houve diferenças significantes entre medidas manuais e computadorizadas. Conclusões: A proporção existente entre os segmento septal e o segmento ântero-posterior, do anel da valva tricúspide normal em humanos, é igual a 1 : 2,43. A secção e retificação do anel tricuspídeo altera as medidas de seus segmentos e suas relações / Abstract: Objective: The purpose of this study was to determine the proportion among the segments of the human tricuspid valve annulus. Methods: Descriptive autopsy study of 30 human hearts, without fixation, with less than six hours of post-mortem period, without congenital or acquired lesions and without tricuspid regurgitation. The tricuspid valve insufficiency was excluded by infusion of pressured water in the right ventricle with closed pulmonary valve. Digital images of the tricuspid ring on anatomical position and on flattened state were analyzed by specific software. Computerized measurements of the perimeter, septal segment, anteroposterior segment and the linear distance between the anteroseptal and posteroseptal commissures were obtained on anatomical position. Computerized and manual measurements of the perimeter, septal, anterior and posterior segments were obtained on flattened state. The measurements were demonstrated and compared on the two different situations, anatomical position and flattened. The computerized measurements were compared with the manual ones. Results: The mean values of the perimeter, septal and anteroposterior segments of the tricuspid ring, obtained by computerized measurements on anatomical position were: 105mm (±12.7), 30.6mm (±3.7) e 74mm (±9.4), respectively. The mean linear distance between the anteroseptal and posteroseptal commissures was 28.9mm (±3.4). On the flattened state and by computerized measurements, the mean value of the perimeter was 117.5mm (±13.3) and of the septal, anterior e posterior segments were respectively: 32mm (±3.7), 46.3mm (±8.3) e 39.1mm (±8.5). The mean ratio between the antero-posterior and septal segments was 2.43 (±0.212) on the anatomical position and on flattened state was 2.67 (±0.304). Statistical differences were observed in the measurements of perimeter (p<0.0001), septal segment (p=0.003) e antero-posterior segment (p<0.0001) on the two situations. Statistical difference also occurred on the ratios between the antero-posterior and septal segments (p=0.0005). The mean values obtained by manual measurements of the tricuspid ring on flattened state were: 118.5mm (±12.7), 32.6mm (±3.4), 46.6mm (±7.7) e 39.3mm (±7.9), respectively for perimeter, septal, anterior and posterior segments. There weren¿t statistical differences on computerized and manual measurements. Conclusions: The proportion between the septal and antero-posterior segments of the normal human tricuspid valve is 1 : 2.43. The attitude of flatting the tricuspid ring to measure the segments, changes their values and the ratios between them / Mestrado / Cirurgia / Mestre em Cirurgia

Les pathologies valvulaires aortiques sont des pathologies plurifactorielles, comportant un déterminisme génétique indiscutable mais peu caractérisé. Ma thèse a pour but d’étudier le rôle du facteur de transcription Krox20 au cours du développement et de la maturation valvulaire à travers l’analyse de modèles murins. Nous avons montré que ce gène est nécessaire au développement et à la maturation de la valve aortique. L’invalidation de Krox20 chez la souris conduit à une hypertrophie des feuillets aortiques dès les stades fœtaux et à des insuffisances aortiques chez l’adulte. Ces anomalies sont associées à des défauts d’organisation de la matrice extracellulaire en partie liée à une régulation directe de l’expression des collagènes de type I et III. 25% des souris déficientes pour Krox20 présentent une bicuspidie de la valve aortique. Nous avons observé une diminution de l’expression de eNos chez ces mutants et pu mettre en évidence une interaction génétique entre Krox20 et eNos. De plus, nous avons identifié une sous population de cellules des crêtes neurales cardiaques impliquées dans l’apparition de la bicuspidie chez les mutants Krox20. Afin d’explorer le rôle de Krox20 dans la calcification de la valve aortique, nous avons étudié les conséquences de la surexpression de ce gène dans un modèle et montré que lcela induisait une activation de gènes pro-fibrotiques et pro-ostéogénique sans conduire à des dépôts calciques. Krox20 est donc un facteur de transcription important pour la valvulogenèse et à l’homéostasie valvulaire chez l’adulte. Mes travaux ont contribué à l’identification de Krox20 comme gène candidat potentiel aux valvulopathies rencontrées chez l’homme. / Long seen as a consequence of aging and mechanical wear of aortic cusps, aortic valve diseases are currently considered multifactorial diseases, with an indisputable genetic determinism but not well characterized. My thesis aims to study the role of the transcription factor Krox20 during development and maturation of the valve through the analysis of mouse models. We have shown that this gene is necessary for the development and maturation of the aortic valve. Indeed, the deletion of Krox20 in the mouse leads to thickened aortic leaflets from the fetal stage and the onset of aortic valve disease in adults. These anomalies are associated with defects in the organization of the extracellular matrix and more particularly to direct regulsation of collagen type I and type III expression. Our analysis showed that 25% Krox20-/- mice have a bicuspid aortic valve. The analysis of this model has allowed us to identify a population of cardiac neural crest cells involved in the occurrence of this phenotype. In addition, we were able to observe a down regulation of eNos in Krox20-/- embryos and show a genetic interaction between Krox20 and eNos. To address the role of Krox20 in the process of calcification of the aortic valve, we have studied the effects of its overexpression. Our preliminary results indicate that this overexpression leads to activation of pro-fibrotic and pro-osteogenic genes, however, this is not sufficient to induce calcification of aortic valve leaflets.Therefore Krox20 is important for valvulogenesis but also for valvular homeostasis in the adult. My work has contributed to the identification of a potential candidate gene involved in human valve diseases.

Patients with mechanical heart valves who present with intracranial haemorrhage are initially treated by reversing their coagulopathy. However, these patients will ultimately require that their oral anticoagulant be restarted. The time at which oral anticoagulants are restarted is critical since restarting too early may increase the risk of recurrent bleeding, while withholding anticoagulants increases the patient’s risk of thromboembolic events. The ideal time to restart patients on their oral anticoagulant medication is defined as the time at which all these risks are minimized. This thesis includes a systematic review and meta-analysis of the literature. The main outcomes were recurrent haematoma, valve thrombosis, stroke and peripheral emboli. Results were stratified by types of intracranial haemorrhage. We also conducted a survey to gain insight into current practices of neurosurgeons and thrombosis experts in Canada and USA when they are faced with deciding on anticoagulant restart times in patients with ICH. Results were stratified by type of intracranial bleed and participants’ characteristics and demographics. The systematic review identified that the ideal time for restarting anticoagulant therapy in patients following an ICH is unknown. Meta-analysis was limited by the heterogeneity of the studies. The survey results indicated that physicians had a wide range of practice and that their practice was dependent on the patient’s clinical features, but many physicians would restart oral anticoagulants between 4 and 14 days after the haemorrhage. For this reason we have proposed a multi centre cohort study to investigate the safety and efficacy of restarting patients on anticoagulation therapy between day 5 and 9 post haemorrhage. A full study protocol is presented in this thesis.

Este trabalho descreve a reação de reticulação alternativa do pericárdio bovino com os acetais do glutaraldeído, preparados a partir da solução de glutaraldeído na presença do etanol em meio ácido. Os acetais difundem para dentro da matriz colagênica, e a reticulação ocorre após a desproteção dos grupos aldeídicos com uma amina terciária. O material obtido sob estas condições mostrou as propriedades biológicas e mecânicas similares ou superiores àqueles descritos para o pericárdio bovino reticulado pelo procedimento convencional com glutaraldeído, e provavelmente, com resultados de uma distribuição e natureza química mais homogênea das reticulações formadas, devido à ausência das reticulações polímeros de glutaraldeído. As biopróteses manufaturadas com pericárdio reticulado com acetais do glutaraldeído, também mostraram durabilidade superior e foi menos suscetível ao processo de calcificação, como determinado em implantes subcutâneos em ratos. Resultados preliminares de teste à fadiga e performance hidrodinâmica foram caracterizados por um comportamento similar àqueles materiais tratados convencionalmente sugerindo que, o pericárdio reticulado com acetais do glutaraldeído pode ser um procedimento alternativo e mais eficiente na manufatura das biopróteses, particularmente com respeito à calcificação, um dos maiores problemas encontrados pós-implante. / This work describes the cross-linking of bovine pericardium with glutaraldehyde acetals, which are its protected forms. The acetals, prepared from a glutaraldehyde solution in the presence of ethanol in acidic media was al/owed to diffuse within the collagen matrix, and cross-linking achieved by deprotection with a tertiary amine. The material obtained under this conditions showed biological and mechanical properties similar or superior to those described for bovine pericardium crosslinked by conventional procedure with glutaraldehyde, and probably, as a results of a more homogeneous distribution and chemical nature of the formed crosslinks, that is the absence of polymeric cross-links. Bioprostheses manufactured with glutaraldehyde acetals cross-linked bovine pericardium, also showed higher durability and was less susceptible to calcification process, as determined in subcutaneous implant in rats. Preliminary results on fatigue test and hydrodynamic performance were characterized by a behavior similar to those observed for conventional/y treated materials suggesting that, glutaraldehyde acetals crosslinked bovine pericardium may be an alternate and more efficient procedure in the manufacture of bioprostheses, particularly in respect to calcification, one of the major problems found post-implantation.