Understanding the mechanisms behind unexplained abnormal heart rhythms is important for diagnosis and prevention of arrhythmias. Many studies have investigated the mechanisms at organ, tissue, cellular and molecular levels. There is considerable information available from tissue level experiments that investigate local action potential properties and from optical imaging to observe activity propagation properties at an organ level. By combining those electrophysiological properties together, in the present study we developed a simulation model that can help in estimation of the resulting body surface potentials from a specific electrical activity pattern within the myocardium. Some of the potential uses of our model include: 1) providing visualization of an entire electrophysiological event, i.e. surface potentials and associated source which would be optical imaging data, 2) estimation of QT intervals resulting from local action potential property changes, 3) aiding in improving defibrillation therapy by determining optimal timing and location of shocks.

The heart is a complex organ and much is still unknown about its mechanical function. In order to use simulations to study heart mechanics, fluid and solid components and their interaction should be incorporated into any numerical model. Many previous studies have focused on myocardium motion or blood flow separately, while neglecting their interaction. Previous fluid-structure interaction (FSI) simulations of heart mechanics have made simplifying assumptions about their solid models, which prevented them from accurately predicting the stress-stain behaviour of the myocardium. In this work, a numerical model of the canine left ventricle (LV) is presented, which serves to address the limitations of previous studies. A canine LV myocardium material model was developed for use in conjunction with a commercial finite element code. The material model was modified from its original form to make it suitable for use in simulations. Further, numerical constraints were imposed when calculating the material parameter values, to ensure that the model would be strictly convex. An initial geometry and non-zero stress state are required to start cardiac cycle simulations. These were generated by the static inflation of a passive LV model to an end-diastolic pressure. Comparisons with previous measurements verified that the calculated geometry was representative of end diastole. Stresses calculated at the specified end diastolic pressure showed complex spatial variations, illustrating the superiority of the present approach over a specification of an arbitrary stress distribution to an end-diastolic geometry. In the third part of this study, FSI simulations of the mechanics of the LV were performed over the cardiac cycle. Calculated LV cavity pressures agreed well with previous measurements during most of the cardiac cycle, but deviated from them during rapid filling, which resulted in non-physiological backflow. This study is the first one to present a detailed analysis of the temporal and spatial variations of the properties of both the solid and the fluid components of the canine LV. The observed development of non-uniform pressure distributions in the LV cavity confirms the advantage of performing FSI simulations rather than imposing a uniform fluid pressure on the inner surface of the myocardium during solid-only simulations.

The neural cell adhesion molecule L1 is a member of the immunoglobulin superfamily and it mediates many adhesive interactions during brain development. Mutations in the L1 gene are associated with a spectrum of X-linked neurological disorders known as CRASH or L1 syndrome. The objective of this thesis was to use the zebrafish model to investigate the molecular mechanisms of L1 functions and the pathological effects of its mutations. Zebrafish has two L1 homologs, L1.1 and L1.2. Inhibition of L1.1 expression by antisense morpholino oligonucleotides resulted in phenotypes that showed resemblances to L1 patients. However, knockdown of L1.2 expression did not result in notable neural defects. Furthermore, analysis of the expression pattern of L1.1 has led to the discovery of a novel soluble L1.1 isoform, L1.1s. L1.1s is an alternatively spliced form of L1.1, consisting of the first four Ig-like domains and thus a soluble secreted protein. L1.1 morphants exhibited disorganized brain structures with many having an enlarged fourth/hindbrain ventricle. Further characterization revealed aberrations in ventricular polarity, cell patterning and proliferation and helped differentiate the functions of L1.1 and L1.1s. While L1.1 plays a pivotal role in axonal outgrowth and guidance, L1.1s is crucial to brain ventricle formation. Significantly, L1.1s mRNA rescued many anomalies in the morphant brain, but not the trunk phenotypes. Receptor analysis confirmed that L1.1 undergoes heterophilic interactions with neuropilin-1a (Nrp1a). Peptide inhibition studies demonstrated further the involvement of L1.1s in neuroepithelial cell migration during ventricle formation. In the spinal cord, spinal primary motoneurons expressed exclusively the full-length L1.1, and abnormalities in axonal projections of morphants could be rescued only by L1.1 mRNA. Further studies showed that a novel interaction between the Ig3 domain of L1.1 and Unplugged, the zebrafish muscle specific kinase (MuSK), is crucial to motor axonal growth. Together, these results demonstrate that the different parts of L1.1 contribute to the diverse functions of L1.1 in neural development.

Thesis (Ph.D.)--Biomedical Engineering, Georgia Institute of Technology, 2008. / Committee Chair: Oshinski, John N.; Committee Member: Fyfe, Derek A.; Committee Member: León, Angel R.; Committee Member: Skrinjar, Oskar; Committee Member: Taylor, W. Robert.

Το πεδίο έρευνας της παρούσας διδακτορικής διατριβής είναι η υπολογιστική καρδιολογία και συγκεκριμένα η μέτρηση όγκου δεξιάς κοιλίας με χρήση υπερήχων σε καθετήρα πνευμονικής αρτηρίας (ΚΠΑ) για την αποτελεσματικότερη διαχείριση των βαριά πασχόντων ασθενών. Μέχρι τώρα ο ΚΠΑ μετράει μόνο τις πιέσεις ενδοκοιλοτικά. Τα αποτελέσματα από τη χρήση του δεν είναι επαρκώς ενθαρρυντικά. Έχει βρεθεί ότι για την καλύτερη αντιμετώπιση των βαριά πασχόντων στην μονάδα εντατικής θεραπείας (ΜΕΘ), ή στην μονάδα εμφραγμάτων, ή ακόμα και κατά την προετοιμασία ή τη διάρκεια μιας σοβαρής χειρουργικής επέμβασης, σημαντική παράμετρος πέρα από την πίεση είναι ο τελοσυστολικός και ο τελοδιαστολικός όγκος της δεξιάς κοιλίας. Αυτές οι παράμετροι συνδυαζόμενες με τις πιέσεις, προσφέρουν σαφώς καλύτερη εκτίμηση και αποτελεσματικότερη αιμοδυναμική διαχείριση των βαριά πασχόντων ασθενών με απώτερο στόχο την ελάττωση της νοσηρότητας και θνησιμότητας. Γι’ αυτό το λόγο μοντελοποιήθηκε σύστημα μέτρησης όγκου δεξιάς κοιλίας από εικόνες MRI (μαγνητικού συντονισμού) με προσομοίωση υπερήχων. Επίσης το γεγονός ότι δεν υπάρχει μέθοδος υπολογισμού όγκου ενδοκοιλιακά που να συνδυάζεται με τον δεξιό καθετηριασμό, καθιστά την παρούσα διατριβή ως καινοτόμα αφ’ ενός στον υπολογισμό του όγκου της δεξιάς κοιλίας και αφ’ ετέρου στην διαχείριση της αιμοδυναμικής κατάστασης των βαριά πασχόντων. / The research field of this PhD thesis is the computational cardiology and more specifically the right ventricle’s volume measurement using ultrasound technology on the pulmonary artery catheter (PAC) for the effective management of critically ill patients. Hitherto, right cardiac catheterization with a pulmonary artery catheter provides only intracavity pressure measurements. Several studies showed that the use of PAC in critically illness does not make any effect in patient management. It was found that for the reliable management of critical ill patients in intensive care unit (ICU), or in infarctions unit, or even during serious surgery, pressures, is the right ventricle end-diastolic and end-systolic volume. The combination of those parameters with pressures, provides obviously better estimation and effective hemodynamic management of critically ill patients seeking in mortality and morbidity reduction. For that reason, a right ventricle’s volume measurement system was modeled from cardiac MRIs with ultrasound simulation. The fact that there is not any intraventricular volume calculation method combined with right catheterization, makes this PhD thesis innovative as the right ventricle’s volume and the hemodynamic management of critically ill patients regards.

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Agradecemos a compreensão on 2018-04-04T14:03:35Z (GMT) / Submitted by Roberta Martins Crivelaro null (robertamc.vetunesp@hotmail.com) on 2018-04-04T15:29:19Z No. of bitstreams: 1 Crivelaro_RM_Tese.pdf: 54429572 bytes, checksum: 4d5ef09be8bb95df6635d4fb516cef61 (MD5) / Approved for entry into archive by Alexandra Maria Donadon Lusser Segali null (alexmar@fcav.unesp.br) on 2018-04-04T18:00:56Z (GMT) No. of bitstreams: 1 crivelaro_rm_dr_jabo.pdf: 54429572 bytes, checksum: 4d5ef09be8bb95df6635d4fb516cef61 (MD5) / Made available in DSpace on 2018-04-04T18:00:56Z (GMT). No. of bitstreams: 1 crivelaro_rm_dr_jabo.pdf: 54429572 bytes, checksum: 4d5ef09be8bb95df6635d4fb516cef61 (MD5) Previous issue date: 2018-02-05 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / As doenças cardiovasculares constituem grande problema de saúde pública. A necessidade do entendimento do processo de remodelação cardíaca tem acarretado em aumento do número de pesquisas envolvendo terapias biológicas. Neste contexto, peixes teleósteos emergem como opção de modelo experimental, pois possuem homologia morfofuncional e imunológica com mamíferos. Tilápias-do-Nilo (Oreochromis niloticus) já vêm sendo empregadas no estudo de diversas doenças que afetam seres humanos. Com a presente pesquisa, objetivou-se desenvolver técnica de acesso videocirúrgico e induzir lesão cardíaca mecânica, em tilápias-do-Nilo; avaliar a eficácia da metadona no controle da dor associada à lesão; e caracterizar os mecanismos de remodelação do miocárdio ventricular, empregando-se avaliações por eletrocardiograma e por microscopias. As avaliações foram conduzidas antes, 1 h depois, e transcorridos 7, 14, 30, 60 e 90 dias da lesão cardíaca. O acesso à cavidade celomática foi realizado utilizando-se um punch de biopsia de 3 mm, permitindo a introdução de endoscópio para posterior amputação do ápice do coração. O procedimento foi executado rapidamente e com baixo índice de mortalidade transoperatória (5,60%) e pós-operatória (3,38%). Aproximadamente 6% de tecido cardíaco, apresentando epicárdio e miocárdio, foi removido com a pinça de biopsia, sendo que a videocirurgia permitiu boa visibilização interna, padronização do tamanho da lesão e alta precisão. A avaliação da analgesia fornecida pela metadona foi realizada por meio de parâmetros fisiológicos e comportamentais. Os resultados demonstraram que, na dose empregada, a metadona não possuiu efeito analgésico em tilápias-do-Nilo, contudo, o tempo de recuperação da anestesia foi maior entre os animais que receberam metadona, sugerindo um possível efeito sedativo do fármaco. Os ventrículos da tilápia-do-Nilo, após lesão, não apresentaram evidências de regeneração e evoluíram para um processo de remodelamento caracterizado pelos espessamentos das paredes do ventrículo e do epicárdio, pela hipertrofia dos cardiomióticos, e por alterações em atividade elétrica. Mudanças no estado ordenado de agregação do colágeno intersticial, no tamanho e no formato dos núcleos dos cardiomiócitos, e na supraorganização da cromatina nuclear dos cardiomiócitos, bem como presença de células poliplóides, de células necróticas e de células apoptóticas foram observadas. Em conclusão, a tilápia-do-Nilo parece ser um bom organismo modelo para estudos em cardiologia experimental, uma vez que seu ventrículo, após amputação do ápice do coração, acumula muitas das alterações vistas em corações de pacientes humanos cardiopatas. Vantagens adicionais referentes ao emprego de tilápias-do-Nilo em pesquisas incluem o tamanho dos animais, o que possibilita a utilização de técnicas menos onerosas; e a facilidade de alojamento e de manutenção de um grande número de indivíduos num espaço reduzido, com baixa taxa de mortalidade. / Cardiovascular disease are a public health big problem. The need for understanding cardiac repair mechanism has increased the number of researches biologic therapy field. In this context, teleost fish show as a experimental model, as they have morpho-functional and immunologic homology whit mammals. Nile tilapia (Oreochromis niloticus) has been used to study several diseases that affect humans. The present study aimed to develop a video surgery access and mechanically induce cardiac injury in Nile tilapia; to evaluate the analgesic activity of methadone in effectively control the pain associated with the injury; and characterize myocardial repair mechanisms by microscopy and electrocardiogram analysis. Data were recorded before cardiac injury and then 1 hour, 7, 14, 30, 60 and 90 days after cardiac injury. The access to coelomatic cavity was made with a 3-mm biopsy punch, allowing the passage of an endoscope for amputation of the cardiac apex. The procedure was quickly performed with intraoperative (5.6%) and post-operatory (3.38%) low mortality rates. Approximately 6% cardiac tissue, including epicardium and myocardium were removed with the biopsy forceps, once video surgery allowed good visualization, standard lesion areas and great precision. To evaluate the analgesic effect of methadone, physiological and behavioral parameters were recorded. Results show that in the dose used, methadone did not show analgesic effect in Nile tilapia. However, recovery time was longer in fish that received methadone, suggesting a sedative effect of the drug in the specie. The ventricles of Nile tilapia, after lesion, did not showed any evidence of regeneration, progressing for a remodeling process, characterized by a thicker ventricle wall and epicardium, by cardiomiocytes hypertrophy, and changes in electrical activity. Changes in the interstitial collagen aggregation state, size and shape of cardiomiocytes nuclei, and in the supra-organization of nuclear chromatin of cardiomiocytes, as well as presence of ploydy, necrotic and apoptotic cells, were also oberved It was concluded that Nile tilapia seems to be a good experimental model organism for experimental cardiology studies, once its ventricle, after have its apex amputated, shows many of the alterations observed in hearts of humans cardiac patients. Additional advantages regarding the use of Nile tilapia in research include the size of the animals, that allows the use of cheaper techniques; and the practical way to keep a great number of animals in small spaces, with low mortality rates.

Made available in DSpace on 2014-06-11T19:32:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-26Bitstream added on 2014-06-13T21:03:38Z : No. of bitstreams: 1 coleta_kd_dr_botfm.pdf: 391595 bytes, checksum: dde69b55ebd37c6d547a6c2e6321775d (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Pacientes com doença pulmonar obstrutiva crônica (DPOC) apresentam risco elevado para eventos cardiovasculares. Entretanto, existem poucos estudos sobre a função do ventrículo esquerdo (VE) nesses pacientes e os resultados são controversos. Os objetivos deste estudo foram: analisar a estrutura e função do ventrículo direito (VD) e câmaras cardíacas esquerdas, por meio de Dopplerecocardiografia, em pacientes com DPOC e avaliar a associação entre as variáveis ecocardiográficas e as variáveis clínicas relevantes. Foram avaliados 45 pacientes com DPOC (idade: 65,8 ± 10,6 anos, 64% homens): 17 pacientes com DPOC leve a moderada (grau I e II) provenientes do Serviço de Pneumologia da Faculdade de Medicina de Botucatu (FMB) e 28 pacientes com DPOC muito grave (grau IV) acompanhados no Ambulatório de Oxigenoterapia da FMB. Os critérios de inclusão foram: diagnóstico de DPOC, estabilidade clínica e, para os pacientes com DPOC IV, uso de oxigênio domiciliar por período mínimo de três meses. Para o grupo controle foram selecionados 15 indivíduos saudáveis (idade: 64,3 ± 10,1, 47% homens). Os critérios de exclusão foram: imagem ecocardiográfica inadequada, hipertensão arterial sistêmica, diabetes mellitus, doença coronariana, valvopatias, arritmias, patologias respiratórias associadas ou outras patologias cardíacas. Espirometria pré e pós-broncodilatador e oximetria de pulso foram realizadas por todos os sujeitos da pesquisa e gasometria arterial somente para os pacientes com DPOC... / Chronic obstructive pulmonary disease (COPD) is a strong risk factor for cardiovascular events. However, the status of left ventricle (LV) has been less studied and the results are controversial. The objectives were: to analyse the right ventricle (RV) and the left heart chambers structure and function in COPD patients by echocardiogram, and to analyse the association between echocardiographic variables and the relevant clinical variables. Forty-five COPD patients (age: 65,8 ± 10.6 years; 64% male) were evaluated: 17 mild to moderate COPD patients (grade I and II) and 28 very severe COPD patients (grade IV). The inclusion criteria were: COPD diagnosis, clinical stability and home oxygen therapy for at least three months (very severe COPD). The control group consisted of 15 healthy subjects (age: 64.3 ± 10.1 years; 47% male). Exclusion criteria were: poor quality echocardiographic image, history of systemic hypertension, diabetes mellitus, coronary artery disease, valvular heart disease, arrhythmias, associated lung diseases or other heart diseases. Pre and post-bronchodilator spirometry and pulse oximetry were performed in all subjects and arterial gasometry was performed in COPD patients only... (Complete abstract click electronic access below)

Resumo: Pacientes com doença pulmonar obstrutiva crônica (DPOC) apresentam risco elevado para eventos cardiovasculares. Entretanto, existem poucos estudos sobre a função do ventrículo esquerdo (VE) nesses pacientes e os resultados são controversos. Os objetivos deste estudo foram: analisar a estrutura e função do ventrículo direito (VD) e câmaras cardíacas esquerdas, por meio de Dopplerecocardiografia, em pacientes com DPOC e avaliar a associação entre as variáveis ecocardiográficas e as variáveis clínicas relevantes. Foram avaliados 45 pacientes com DPOC (idade: 65,8 ± 10,6 anos, 64% homens): 17 pacientes com DPOC leve a moderada (grau I e II) provenientes do Serviço de Pneumologia da Faculdade de Medicina de Botucatu (FMB) e 28 pacientes com DPOC muito grave (grau IV) acompanhados no Ambulatório de Oxigenoterapia da FMB. Os critérios de inclusão foram: diagnóstico de DPOC, estabilidade clínica e, para os pacientes com DPOC IV, uso de oxigênio domiciliar por período mínimo de três meses. Para o grupo controle foram selecionados 15 indivíduos saudáveis (idade: 64,3 ± 10,1, 47% homens). Os critérios de exclusão foram: imagem ecocardiográfica inadequada, hipertensão arterial sistêmica, diabetes mellitus, doença coronariana, valvopatias, arritmias, patologias respiratórias associadas ou outras patologias cardíacas. Espirometria pré e pós-broncodilatador e oximetria de pulso foram realizadas por todos os sujeitos da pesquisa e gasometria arterial somente para os pacientes com DPOC... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Chronic obstructive pulmonary disease (COPD) is a strong risk factor for cardiovascular events. However, the status of left ventricle (LV) has been less studied and the results are controversial. The objectives were: to analyse the right ventricle (RV) and the left heart chambers structure and function in COPD patients by echocardiogram, and to analyse the association between echocardiographic variables and the relevant clinical variables. Forty-five COPD patients (age: 65,8 ± 10.6 years; 64% male) were evaluated: 17 mild to moderate COPD patients (grade I and II) and 28 very severe COPD patients (grade IV). The inclusion criteria were: COPD diagnosis, clinical stability and home oxygen therapy for at least three months (very severe COPD). The control group consisted of 15 healthy subjects (age: 64.3 ± 10.1 years; 47% male). Exclusion criteria were: poor quality echocardiographic image, history of systemic hypertension, diabetes mellitus, coronary artery disease, valvular heart disease, arrhythmias, associated lung diseases or other heart diseases. Pre and post-bronchodilator spirometry and pulse oximetry were performed in all subjects and arterial gasometry was performed in COPD patients only... (Complete abstract click electronic access below) / Orientador: Irma de Godoy / Coorientador: Katashi Okoshi / Banca: Beatriz Matsubara / Banca: Leonardo Zornoff / Banca: Maria Inês Zanetti Feltrim / Banca: Oliver Augusto do Nascimento / Doutor

Orientador: Marta Helena Krieger / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-15T17:17:07Z (GMT). No. of bitstreams: 1 Wanschel_AmarylisClaudineBonitoAzeredo_D.pdf: 3059995 bytes, checksum: afbb018ffe3bb06b61c7420a0fa4664f (MD5) Previous issue date: 2010 / Resumo: O objetivo deste trabalho foi avaliar a biodisponibilidade do óxido nítrico (NOo) nas disfunções cardiovasculares, especificamente na hipertrofia ventricular esquerda e na aterosclerose. Para tanto, realizamos dois estudos em camundongos deficientes do receptor de LDL (LDLr-/-): o primeiro realizado em continuidade aos estudos desenvolvidos anteriormente em nosso grupo de pesquisa, os quais demonstraram a ação do doador de NOo na prevenção da hipertrofia ventricular esquerda e na proteção contra arritmia via indução do acoplamento adrenoceptor-beta2 (ß2AR) à proteína G inibitória (Gi); e no segundo estudo, foi avaliada a biodisponibilidade de NOo na fase inicial da aterogênese, com objetivo de caracterizar as alterações sistêmicas e locais. No primeiro estudo mostramos que o doador de NOo, S-Nitroso-N-acetilcisteína (SNAC) administrado, promoveu ação cardioprotetora contra o remodelamento cardíaco via redução do estresse oxidativo e apoptose celular, os quais foram determinados pelas medidas ventriculares da produção de superóxido (O-o2) e peróxido de hidrogênio (H2O2) e pelo índice de morte celular por apoptose. Esta ação cardioprotetora foi vista no aumento da expressão e no conteúdo de S-nitrosação do ß2AR. Estes efeitos foram associados à cardioproteção contra a arritmia via indução do acoplamento ß2AR à Gi. O objetivo do segundo estudo foi avaliar a biodisponibilidade de NOo na fase inicial da aterogênese em camundongos LDLr-/- no curso temporal de 15 a 60 dias de dieta, com a quantificação de parâmetros sistêmicos representados pela pressão arterial, perfil lipidêmico e ateroma, bem como de parâmetros locais representados pela atividade e expressão da via NO/NOS e suas modificações póstraducionais no processo inflamatório via CD40-CD40L. Camundongos LDLr-/-submetidos à dieta rica em gordura apresentaram progressão do tamanho do ateroma no curso temporal analisado, contudo não foi associado a similares incrementos nos níveis de dislipidemia. Não foram detectadas alterações na pressão arterial do fenótipo hipertenso deste animal. Contudo, localmente foi verificado incremento na atividade da eNOS via fosforilação de resíduos de serina 1179 (S1179) em 30 dias de dieta rica em gordura, que pode ser considerado um mecanismo emergencial à aterosclerose . Posteriormente, com a evolução do ateroma (60 dias) houve redução desta ativação, bem como do conteúdo de proteínas S-nitrosadas. O desenvolvimento de ateroma em 30 e 60 dias induzido pela dieta mostrou aumento da atividade inflamatória por meio da denitrosação de tióis críticos da via CD40. Portanto, a análise das alterações no curso temporal apresentou somente mudanças locais como alteração na biodisponibilidade de NOo, ativação inflamatória via denitrosação do receptor CD40 e redução do conteúdo de S-nitrosação total, enquanto as alterações sistêmicas neste período de tempo ainda não são evidentes / Abstract: The objective of this study was to evaluate the bioavailability of nitric oxide (NOo) in cardiovascular disorders, specifically on the left ventricular hypertrophy and atherosclerosis. Therefore, we performed two studies with LDL receptor-deficient mice (LDLr-/-): the first one was performed in sequence to the studies previously developed in our research group, which showed the NOo donor action on the prevention of left ventricular hypertrophy and protection against arrhythmia via induction of the coupling from beta adrenoceptor-2 (ß2AR) to the inhibitory G protein (Gi); and the second study,it was evaluated the bioavailability of NOo to characterize the systemic and local alterations in the early stages of atherogenesis. The first study showed that the administration of NOo donor S-Nitroso-N-Acetylcysteine (SNAC) promoted cardioprotective action by blocked the cardiac remodeling through reduction of oxidative stress and of apoptosis, which were determined by measures of ventricular superoxide (O-o2) and hydrogen peroxide (H2O2) production and the cell death index, respectively. This cardiprotective action was charactherized by the increase of expression and content of S-nitrosation of ß2AR. These effects were associated with cardioprotection against arrhythimia via induction of ß2AR coupling Gi. The objective of the second study was to evaluate the bioavailability of NOo in the LDLr-/- mice early atherogenesis in LDLr-/ - mice from 15 to 60 days, with the quantification of systemic parameters represented by the blood pressure, lipidemic profile and atheroma as well as local ones represented by the activity and expression of NO/NOS pathway and its post-translational modifications on the inflammatory process via CD40- CD40L. Mice LDLr-/ - maintained on high-fat diet showed progression of atheroma size, although it was not associated with similar increase in dyslipidemic profile. No changes in blood pressure were detected in the hypertensive phenotype of this animal. However, increased activity of eNOS via phosphorylation of Ser1179 (S1179) at 30 days of high-fat diet was detected and it can be considered an emergential mechanism to early atherosclerosis. The development of atheroma (60 days) blocked that activation as well as the protein content of S-nitrosated. The atheroma induced at 30 and 60 days by high-fat diet revealed increase inflammatory activity through denitrosation of critical thiols via CD40. Therefore, the analysis of changes in this time course showed only local changes as changes on NOo bioavailability alteration inflammatory activation via denitrosation of CD40 receptor and the content of total S-nitrosation reduction. However, systemic changes in this period of time have not been evident yet / Doutorado / Fisiologia / Doutor em Biologia Funcional e Molecular

Neste trabalho foi realizada a caracterização de um poliuretano derivado de óleo vegetal para ser utilizado na confecção de dispositivos de assistência ventricular, DAVs. Esses dispositivos são muito importantes na área cardiovascular, pois, possuem a função de suprir a falha dos ventrículos direitos ou esquerdo do coração durante o bombeamento em casos de transplante. Para que esse material seja apto para ser utilizado, precisa-se ter propriedades mecânicas, térmicas e biológicas compatíveis com as necessidades médicas da área cardiovascular. Neste estudo foram utilizadas as técnicas de ensaio mecânico de tração e compressão, as técnicas termoanalíticas DMA, TGA, DSC, bem como espectroscopia de absorção na região do infravermelho. Para os ensaios biológicos foram feitos os teste de tempo de coagulação sanguínea (método Lee White) e o estudo de crescimento celular acompanhado por análise de microscopia eletrônica de varredura (MEV). Os resultados obtidos nos ensaios mecânicos mostraram que o poliuretano possui propriedades que não comprometem sua utilização na confecção dos DAVs. Com relação às análises térmicas, os resultados obtidos pelas curvas DMA mostraram que o poliuretano aumenta seu grau de cura e sua rigidez com o tratamento térmico. As curvas TG e as TG/DSC-FTIR mostram que o poliuretano é termicamente estável e não libera nenhum tipo de substância prejudicial ao ser humano até a temperatura de 200°C, viabilizando uma condição de serviço satisfatória a temperatura corpórea entre 36ºC e 40°C. Os testes biológicos demonstraram que o poliuretano possui potencial para ser utilizado em dispositivos médicos que entram em contato com o sangue, tornando-se necessários estudos para a sua total comprovação de ser um material hemocompatível. / In this study the characterization of a polyurethane derived from vegetable oil was studied for the use in the production of ventricular assistance devices, VADs. These devices are very important in the cardiovascular area, therefore they have the function of supplying the failure of the right or left ventricles of the heart while pumping in transplants. For this material to be used in this application, it must have mechanical, thermal and biological properties compatible with the medical require of the cardiovascular area. In this study was to used the techniques of mechanical tensile and compressive, the thermoanalytical techniques such as DMA, TGA, DSC and absorption spectroscopy in the infrared region. The biological analysis were the test of blood coagulation time (Lee White method) and the study of cellular growth measured by scanning electron microscopy (SEM). The results obtained in the mechanical tests showed that the polyurethane has properties that do not compromise their use in the production of VADs. In relation the thermal analysis of the results obtained by DMA, the curves showed that the polyurethane increases its cure and rigity degrees with thermal treatment. The TG and TG/DSC-FTIR curves showed that the polyurethane is thermally stable does not release any prejudicial substances to the human body until the temperature of 200°C, enabling a satisfactory service condition to body temperature between 36 and 40°C. The biological tests showed that the polyurethane has the potential to be used in medical devices that come into contact with blood, however it\'s needing more studies for its full proof of being a hemocompatible material.