A Síndrome de Marfan (MFS) é uma doença autossômica dominante do tecido conjuntivo, que acomete principalmente os sistemas esquelético, ocular e cardiovascular. O fenótipo cardiovascular, em especial o aneurisma de aorta, é responsável pela maior parte da morbi-mortalidade. MFS é resultante da mutação da fibrilina-1, uma glicoproteína que além de ser um dos principais componentes estruturais da matriz extracelular, tem como função a regulação da atividade do TGF-Beta, por meio de seu sequestro mecânico na matriz extracelular. No entanto, os mecanismos pelos quais a mutação da fibrilina-1 determina aneurismas de aorta torácica com elevada variabilidade fenotípica são ainda pouco elucidados. Um alvo central na fisiopatologia do aneurisma são células musculares lisas vasculares (VSMC), que constituem a maior porção da camada média da aorta. Por meio do controle do tônus contrátil da aorta, da estrutura do citoesqueleto e da interação com a matriz extracelular controlam a estrutura da aorta e a resposta a estímulos patológicos. Mutações que geram perda de função no aparato contrátil de VSMCs prejudicam força contrátil e respostas mecanoadaptativas. No entanto, o papel da VSMC na MFS foi pouco estudado. Neste estudo, investigamos se alterações do fenótipo de VSMCs correlacionam-se a prejuízos na geração de força e alterações em respostas biomecânicas em VSMC cultivadas a partir de aortas obtidas de camundongos com ou sem a mutação mgDeltalpn para MFS na fase inicial (3 meses) e tardia (6 meses). Aos 3 meses de evolução, detectamos importantes alterações fenotípicas nas MFS-VSMC, com maior proliferação celular e redução de alguns marcadores de diferenciação (calponina-1), porém aumento de outros (alfa-actina e SM22). Ao mesmo tempo, ocorreu mudança morfológica, com aumento da área da célula e perda do formato fusiforme. Tais alterações foram consistentes com transição para fenótipo mesenquimal, que foi confirmada pela expressão de vários marcadores. Marcadores de estresse do retículo endoplasmático (RE) aumentaram em MFS-VSMC vs. WT (wild-type) -VSMC condição basal, sem aumento pós estiramento mecânico. Correção da matriz de fibrilina-1 defeituosa em MFS-VSMC promoveu reversão de alguns aspectos do fenótipo, mas não do estresse do RE. MFS-VSMC mostra perfil protêomico divergente de WT-VSMC, em particular menor expressão de proteínas regulatórias do citoesqueleto. Importante, MFSVSMC têm reduzida capacidade de gerar força de tração quando semeadas em substrato com rigidez fisiológica e geram momento contrátil in vitro, no entanto, sem perda na capacidade de adesão. Importante, MFS-VSMC têm forte atenuação da resposta de tração a aumentos da rigidez do substrato. Em paralelo, MFS-VSMC exibem menor densidade em fibras de estresse de actina em relação às WT-VSMC. A maioria destas alterações não foram observadas aos 6 meses de evolução da doença. Os dados indicam que na fase precoce da doença, MSF-VSMC exibem mudanças fenotípicas que vão além de uma simples modulação fenotípica, com aspectos de transição mesenquimal e reduzida capacidade de geração de força tensional associada não à adesão celular, porém à menor capacidade de geração de fibras de estresse de actina. Estes mecanismos, descritos pela primeira vez, contribuir para elucidar a fisiopatologia da MFS, com alguns aspectos comuns, porém outros distintos de outras modalidades de aneurisma de aorta / Marfan Syndrome (MFS) is an autosomal dominant connective tissue disease affecting to variable extents the musculoskeletal, ocular and cardiovascular systems. Cardiovascular phenotype and in particular thoracic aorta aneurysm/dissection (TAAD), is responsible for the bulk of disease morbimortality. MFS is due to mutations in fibrillin-1, one of the main structural proteins of the extracellular matrix (ECM), which in addition regulates TGF-Beta activity by means of its physical retention in the ECM. However, mechanisms by which fibrillin-1 mutation determines TAAD with elevated phenotypic variability are yet poorly understood. Vascular smooth muscle cells (VSMC), the main component of aortic medial layer, are central targets of aneurysm pathophysiology in general. By exerting regulation of contractile tone, cytoskeletal structure and ECM interaction, VSMC control aortic structure and response to pathologic stimuli. Mutations that promote loss of VSMC contractile apparatus impair contractile function and mechanoadaptative responses and associate with distinct types of TAAD. However, the role of VSMC mechanobiology in MFS pathophysiology is poorly known. In this study, we investigated whether VSMC loss of force-generating capacity occurs in MFS and whether it associates with specific changes in cell phenotype. Biomechanical VSMC responses were assessed in cells cultured from aortas collected from mice with the mgDeltalpn MFS mutation at early (3-monthold mice, the main focus of our study) and advanced (6-month-old mice) stages of disease evolution. At 3 months of disease evolution, we detected important phenotypic alterations in MFS-VSMC, with enhanced expression of markers for cellular proliferation and lower expression of some differentiation markers (calponin-1), but, increase in others (SM alfaactin and SM22). In parallel, there were important morphologic changes, with increased VSMC area and loss of its fusiform shape. Such alterations are consistent with a transition towards a mesenchymal-like phenotype, which was confirmed through the expression of several markers. Endoplasmic reticulum (ER) stress markers increased in MFS-VSMC vs. WT (wild-type)-VSMC in basal condition, without augmentation after cyclic mechanical stretching. Replacement of defective fibrillin-1 ECM from MFS-VSMC with a normal fibroblast-derived ECM promoted reversion of some aspects of the phenotype but not of ER stress. MFS-VSMC exhibited a proteomic profile divergent from that of WT-VSMC, particularly with respect to the lower expression of cytoskeleton regulatory proteins. Importantly, MFS-VSMC displayed a lower traction force-generating capacity when seeded in ECM under physiological stiffness and generated an impaired contractile moment in this situation. In particular, MFS-VSMC depicted a strong attenuation of the traction force response to enhanced ECM stiffening. These defects did not occur as a result of lower adhesion structure and decreased adhesion capacity of MFS-VSMC. In parallel, MFS-VSMC exhibited lower density of actin stress fiber vs. WT-VSMC. With 6 months of disease evolution, several of these alterations were not detectable. Both WTVSMC and MFS-VSMC showed reduced capacity of force generation, without evidence of cell senescence. In summary, starting already in the early stages of disease evolution, MSF-VSMC display important phenotypic changes which go beyond a simple reversible phenotypic modulation, with some aspects suggesting a transition mesenchymal-like phenotype, accompanied by reduced force-generating capacity not linked to loss of cell adhesion properties but rather to impaired organization of action stress fibers. These mechanisms, described for the first time, contribute to elucidate MFS pathophysiology, depicting both some aspects in common with the pathophysiology of other types of aortic aneurysm and some aspects peculiar to MFS

Aneurisma de Aorta Abdominal (AAA) é definido como uma dilatação localizada e permanente da parede arterial, geralmente com ocorrência entre as artérias renais e as ilíacas, como conseqüência do enfraquecimento dessa parede ou devido a uma solicitação anormal sobre sua estrutura normal. Essa afecção acomete principalmente a população idosa acima de 65 anos de idade, tendo como principais fatores de risco: tabagismo, hipertensão arterial, histórico familiar e doença obstrutiva crônica pulmonar. A prevalência está aumentando nos últimos anos, havendo uma duplicação dos casos diagnosticados nos Estados Unidos (Bonamigo e Von Ristow, 1999). Hoje o AAA é a 13ª causa de morte nos Estados Unidos, em homens com mais de 65 anos e no caso de aneurisma roto, é a 3ª causa de morte súbita nos Estados Unidos. A mortalidade global do AAA roto está em torno de 80% nos países que têm verificação sistemática e compulsória da causa de óbitos. Isto ocorre devido ao fato de uma hemorragia substancial intra-abdominal geralmente ser acompanhada de atraso no transporte e diagnóstico, e da necessidade de cirurgia de emergência em pacientes idosos que, freqüentemente, tem uma significativa comorbidade renal e cardiopulmonar. Acredita-se que a formação e o crescimento do aneurisma de aorta abdominal são acompanhados do crescimento da tensão na parede da aorta e/ou de uma diminuição da capacidade do tecido de suportar tal tensão. A ruptura ocorre quando a tensão atuante na parede excede a tensão que pode ser suportada pelo tecido. O risco de ruptura aumenta com o crescimento do tamanho do aneurisma, da tensão na parede e é agravado quando associado à hipertensão arterial. No estudo foram obtidos dados morfológicos da região torácica de um paciente com a utilização de tomografia computadorizada multi-fatias. Essas imagens DICOM (Comunicação de Imagens Digitais em Medicina) foram tratadas para selecionar apenas a região de interesse, obtendo-se um modelo tridimensional da aorta infra-renal e artérias ilíacas. A partir daí, foi confeccionado um modelo físico com a utilização de prototipagem rápida. Um simulador cardiovascular controlado por computador foi desenvolvido com o intuito de replicar características fisiológicas e patológicas do sistema cardiovascular humano. Esse modelo de aneurisma foi utilizado para simulação em bancada experimental, onde é possível reproduzir alguns parâmetros como pressão, fluxo, temperatura, resistência e complacência vascular. Também foi gerado um modelo computacional onde os parâmetros obtidos na simulação in vitro foram utilizados como condição de contorno inicial para o estudo computacional. Foram adotados padrões normotenso e hipertenso, e os resultados computacionais e experimentais foram analisados e comparados. O trabalho propõe uma metodologia que possibilite a obtenção de dados anatômicos e hemodinâmicos relativos ao segmento arterial acometido pela afecção, com o objetivo de fornecer informações adicionais no diagnóstico do aneurisma de aorta. / Abdominal Aortic Aneurysm (AAA) is defined as a focal and permanent dilatation of the arterial wall, most often occurring in between the renal and iliac arteries, as consequence of arterial wall weakness or because of an abnormal solicitation of that normal structure. This disease primarily affects elderly population over 65 years of age, and the most important risk factors are smoking, hypertension, family history and chronic obstructive pulmonary disease. In the last years, the prevalence is rising up almost twice the diagnosed cases in the United States (Bonamigo and Von Ristow, 1999). Nowadays, AAA is the thirtieth cause of death in the United States, in the elderly masculine population over 65 years of age, and in case of ruptured aneurysm, it is the third cause of sudden death in the United States. The overall mortality rate is about 80% in countries with systematic and compulsory evaluation of death cause. This is due to the fact that substantial intra-abdominal hemorrhage is often accompanied by delays in transport and diagnoses, and the need for emergency surgery in elderly patients that frequently have significant renal and cardiopulmonary comorbidity. It is suggested that the formation and expansion of the AAA are accompanied by wall stress increasing and / or decreasing in the tissue capacity to withstand this stress. The rupture occurs when the wall stress exceed the stress the tissue can accept. The risk of rupture increases with aneurysm expansion, wall stress increasing and it is exacerbated when associated with arterial hypertension. In the present work, morphological data from thoracic region of the patient was acquired by using multi-slice CT (Computed Tomography). These DICOM images had been treated to select only the interest region, getting a three-dimensional infra-renal aortic and iliac model. Then, it was made a physical model by using rapid prototyping. This model was used for in vitro experimentation in a computer controlled mock system, in which it is possible to replicate physiological and pathological characteristics of human being cardiovascular system. Some parameters such as pressure, flow, temperature, vascular resistance and compliance can be reproduced by the use of a mock circulatory system. These parameters were used as initial boundary conditions in order to calibrate a computational model. It was adopted normotensive and hypertensive patterns and computational and experimental results were analyzed and compared. The paper proposes a methodology which allows the acquisition of anatomical and hemodynamic data on the vessel segment affected by the pathology, with the goal of providing additional information in the diagnosis of aortic aneurysm.

Infektionen im Bereich der Aorta stellen heute noch eine der gravierendsten Komplikationen der rekonstruktiven Gefäßchirurgie dar. Ziel der vorliegenden Arbeit war es, die Effektivität von kryokonservierten Aortenallografts bei der in situ-Behandlung einer manifesten Infektion im Bereich der Aorta tierexperimentell zu evaluieren. Dessweiteren sollte die Rolle der im Rahmen der Kryokonservierung zum Zwecke der Dekontamination eingesetzten Antibiotika untersucht werden. Zu diesem Zwecke erfolgte im in-vitro Experiment die Untersuchung der Antibiotikakonzentration im Gewebe sowie die der Freisetzungskinetik. Am Modell einer durch Staphylococcus epidermidis RP-62 verursachten Protheseninfektion der infrarenalen Bauchaorta des Hundes konnte eine intrinsische Infektionsresistenz der kryokonservierten Aortenallografts nachgewiesen werden. Jedoch scheint die Antibiotikabehandlung der Allografts für die Optimierung des therapeutischen Effektes essentiell zu sein. Die Ergebnisse der in vivo-Experimente werden durch die in vitro-Untersuchungen, ebenso wie durch die Analyse der eigenen klinischen Ergebnisse und der in der Literatur publizierten Daten belegt. Die vorliegende Arbeit kommt zu dem Schluß, daß die Verwendung von kryokonservierten Allografts das Therapiekonzept der Wahl zur Behandlung von Infektionen im Bereich der Aorta darstellt. / Infections of the aorta remain one of the most dreaded complications in reconstructive vascular surgery. The purposes of this study were to evaluate the efficacy of a cryopreserved aortic allograft to treat an established vascular graft infection by the surgical in situ replacement of the infected segment in an animal model, and to investigate the role of antibiotics to decontaminate the allograft during the cryopreservation process. Furthermore, the tissue concentrations of the antibiotic and the kinetics of desorption were investigated in in vitro experiments. A model of prosthetic graft infection by Staphylococcus epidermidis RP-62 (inserted in the infrarenal aorta) in dogs was developed. By in situ replacement of the infected prosthetic graft with a cryopreserved aortic allograft, this study demonstrated an intrinsic resistance to infection of cryopreserved aortic allografts. However, antibiotic loading of the cryopreserved aortic allografts appeared to be essential to obtain optimal therapeutic effects. The results of these in vivo experiments were supported by the findings of our in vitro studies, as well by analysis of our own clinical results and by clinical data published in the medical literature. We conclude that in situ replacement with a cryopreserved allograft is currently the therapy of choice for an aortic infection.

Introdução. As artérias perfurantes comumente são evidenciadas durante a dissecção microcirúrgica para clipagem de aneurismas intracranianos. A oclusão de artérias perfurantes pode ser responsável por infarto encefálico isquêmico e resultados clínicos indesejáveis. O presente estudo objetiva descrever a utilidade da vídeo-angiografia intra-operatória com indocianina verde (VAIICG) na avaliação do fluxo sanguíneo em artérias perfurantes visibilizadas no campo microcirúrgico, durante a clipagem de aneurismas intracranianos. Secundariamente, foi analisada a incidência de artérias perfurantes envolvidas durante a cirurgia de aneurismas intracranianos, e a ocorrência de infarto encefálico isquêmico causado pelo comprometimento das artérias perfurantes. Método. Sessenta pacientes, com 64 aneurismas intracranianos foram tratados cirurgicamente, e prospectivamente incluídos neste estudo. A VAIICG intra-operatória foi realizada com o uso de microscópio neurocirúrgico (Carl Zeiss Co. Oberkochen, Germany) com a tecnologia VAIICG integrada. A presença e o envolvimento de artérias perfurantes foram analisados no campo microcirúrgico durante a dissecção cirúrgica, e durante a clipagem do aneurisma. A patência vascular após a clipagem também foi investigada. Apenas artérias pequenas que não foram visibilizadas nas imagens pré-operatórias de angiografia digital com subtração (ADS) foram consideradas para análise. Resultados. A VAIICG permitiu a visibilização do fluxo sanguíneo em todos os casos que apresentaram artérias perfurantes no campo microcirúrgico. Dentre 36 casos cujas artérias perfurantes estavam visíveis à VAIICG, 11 casos (30,5%) apresentaram relação próxima entre o aneurisma e artérias perfurantes. Em um paciente (9,0%), dentre os 11 casos com relação próxima, a VAIICG evidenciou oclusão de uma artéria perfurante de P1 após a aplicação do clipe, cujo reposicionamento correto restabeleceu imediatamente o fluxo sanguíneo, o qual foi visibilizado com a VAIICG, sem conseqüências clínicas. Quatro pacientes (6,7%) apresentaram infarto pós-operatório em território de artérias perfurantes, sendo que em três deles, as artérias perfurantes estavam ausentes ou distantes do aneurisma clipado. Conclusão. O envolvimento de artérias perfurantes durante a clipagem microcirúrgica de aneurismas intracranianos é comum. A VAIICG intra-operatória fornece informação visual do fluxo sanguíneo em artérias de calibre milimétrico, e seu uso possibilita evitar a oclusão de artérias perfurantes e subseqüente infarto encefálico. / Background. Perforating arteries are commonly involved during the surgical dissection and clipping of intracranial aneurysms. Occlusion of perforating arteries may be responsible for ischemic infarction and poor outcome. The goal of this study was to describe the usefulness of near-infrared indocyanine green videoangiography (ICGA) for the intraoperative assessment of blood flow in perforating arteries that are visible in the surgical field during clipping of intracranial aneurysms. In addition we analyzed the incidence of perforating vessels involved during the aneurysms surgery and the incidence of ischemic infarct caused by compromising of these small arteries. Method. Sixty patients harboring 64 aneurysms were surgically treated and prospectively included in this study. Intraoperative ICGA was performed using a surgical microscope (Carl Zeiss Co. Oberkochen, Germany) with integrated ICGA technology. The presence and involvement of perforating arteries was analyzed in the microsurgical field, during surgical dissection, and during the clip application. Assessment of vascular patency after clipping was also investigated. Only those small arteries that were not visible on preoperative digital subtraction angiography (DSA) were considered for analysis. Results. In all cases in which perforating vessels were found in the microscope field, the ICGA was able to visualize flow. Among 36 cases whose perforating vessels were visible on ICGA, 11 cases (30,5%) presented a close relation between the aneurysm and perforating arteries. In one patient (9,0%), among these 11 cases with close relation, ICGA showed occlusion of a P1 perforating artery after clip application, which led to immediate correction of the clip confirmed by immediate re-establishment of flow visible with ICGA without clinical consequences. Four patients (6,7%) presented with postoperative perforating artery infarct of whom in 3 patients the perforating arteries were either not visible or distant from the aneurysm. Conclusion. The involvement of perforating arteries during clip application for aneurysm occlusion is a usual finding. Intraoperative ICGA provide visual information with regard to patency of these milimetric vessels, which may avoid their occlusion and further ischemic infarction.

Introdução. A morbi-mortalidade durante e após anestesia para aneurismectomia de aorta abdominal é alta, pois esta doença acomete pacientes após a sétima década de vida e que possuem várias doenças concomitantes. Objetivos. Analisar e discutir as condutas anestésicas utilizadas nos períodos pré e intra-operatório no Serviço de Anestesiologia do HCFMRP-USP. Casuística e Método. Foram analisados os prontuários de 104 pacientes submetidos à aneurismectomia de aorta no tocante às condutas utilizadas pelos anestesiologistas para a condução destes casos. Resultados. Apenas um paciente possuía menos de 40 anos de idade, 76,80% estavam na sétima ou oitava década de vida e 88,46% eram do sexo masculino. A hipertensão arterial acometeu 70,19% dos pacientes e 26,92% possuíam coronariopatia. Pacientes com obesidade foram a minoria (26,92%). O ecocardiograma pré-operatório demonstrou que a grande maioria dos pacientes apresentava função ventricular normal. A cirurgia foi realizada em regime de urgência em 7,69% dos casos. A anestesia geral exclusiva foi realizada em 17 pacientes e associada com a peridural em 57 pacientes, com a raquianestesia em 11 e com a raqui-peri combinadas em 19. O tempo cirúrgico variou de 120 a 510 minutos enquanto que o tempo de clampeamento aórtico variou de 30 a 165 minutos. Houve um óbito no período intra-operatório e a causa foi choque hipovolêmico e 10 óbitos até o vigésimo dia pós-operatório. Sessenta e seis pacientes receberam concentrado de papa de hemácias durante o período intra-operatório, mas só em 43,27% desses casos a indicação esteve suportada por exame laboratorial. Oitenta pacientes foram extubados ainda na sala de cirurgia, enquanto que os demais (23) permaneceram intubados no período pós-operatório e 19 necessitaram de suporte ventilatório que teve tempo que variou de 3 a 96 horas com média de 42,31 horas. Apenas quatro pacientes fizeram pós-operatório imediato no Centro de Terapia Intensiva enquanto que os demais permaneceram na Sala de Recuperação Pós-Anestésica. Conclusão. Não existe um protocolo único para a realização de anestesia para aneurismectomia de aorta no HCFMRP-USP e a técnica anestésica utilizada não influenciou o morbi-mortalidade. / Introduction. The morbidity and mortality during and after anesthesia for aneurysmectomy of the abdominal aorta are high since this disease affects patients after the seventh decade of life who have several concomitant diseases. Objectives. To analyze and discuss the anesthetic conducts used during the preoperative and intra-operative periods at the Service of Anesthesiology of HCFMRP-USP. Cases and Method. The medical records of 104 patients submitted to aneurysmectomy of the aorta were analyzed regarding the conducts used by the anesthesiologists for the management of these cases. Results. Only one patient was less than 40 years old, 76.80% were in he seventh or eighth decade of life, and 88.46% were male. Arterial hypertension was present in 70.19% of the patients and 26.92% had coronary artery disease. Obese patients were a minority (26.92%). The preoperative echocardiogram demonstrated that most patients had normal ventricular function. Surgery was performed on an emergency basis in 7.69% of cases. Seventeen patients received exclusive general anesthesia, while general anesthesia was associated with peridural anesthesia in 57, with rachi-anesthesia in 11 and with combined rachi-peridural anesthesia in 19. Surgical time ranged from 120 to 510 minutes and time of aortic clamping ranged from 30 to 165 minutes. One death occurred intra-operatively due to hypovolemic shock and 10 patients died up to the 20th postoperative day. Sixty-six patients received a red blood cell concentrate intra-operatively, but this indication was supported by a laboratory exam in only 43.27% of these cases. Eighty patients were extubated while still in the operating room while the remaining 23 continued to be intubated during the postoperative period and 19 required ventilatory support lasting 3 to 96 hours (mean duration: 42.31 hours). Only four patients spent the immediate postoperative period in the Intensive Care Unit, while the remaining ones stayed in the Post-Anesthesia Recovery Room. Conclusion. There is no single protocol for the application of anesthesia for aneurysmectomy of the aorta at HCFMRP-USP and the anesthetic technique used did not influence morbidity-mortality.

Aneurisma de Aorta Abdominal (AAA) é definido como uma dilatação localizada e permanente da parede arterial, geralmente com ocorrência entre as artérias renais e as ilíacas, como conseqüência do enfraquecimento dessa parede ou devido a uma solicitação anormal sobre sua estrutura normal. Essa afecção acomete principalmente a população idosa acima de 65 anos de idade, tendo como principais fatores de risco: tabagismo, hipertensão arterial, histórico familiar e doença obstrutiva crônica pulmonar. A prevalência está aumentando nos últimos anos, havendo uma duplicação dos casos diagnosticados nos Estados Unidos (Bonamigo e Von Ristow, 1999). Hoje o AAA é a 13ª causa de morte nos Estados Unidos, em homens com mais de 65 anos e no caso de aneurisma roto, é a 3ª causa de morte súbita nos Estados Unidos. A mortalidade global do AAA roto está em torno de 80% nos países que têm verificação sistemática e compulsória da causa de óbitos. Isto ocorre devido ao fato de uma hemorragia substancial intra-abdominal geralmente ser acompanhada de atraso no transporte e diagnóstico, e da necessidade de cirurgia de emergência em pacientes idosos que, freqüentemente, tem uma significativa comorbidade renal e cardiopulmonar. Acredita-se que a formação e o crescimento do aneurisma de aorta abdominal são acompanhados do crescimento da tensão na parede da aorta e/ou de uma diminuição da capacidade do tecido de suportar tal tensão. A ruptura ocorre quando a tensão atuante na parede excede a tensão que pode ser suportada pelo tecido. O risco de ruptura aumenta com o crescimento do tamanho do aneurisma, da tensão na parede e é agravado quando associado à hipertensão arterial. No estudo foram obtidos dados morfológicos da região torácica de um paciente com a utilização de tomografia computadorizada multi-fatias. Essas imagens DICOM (Comunicação de Imagens Digitais em Medicina) foram tratadas para selecionar apenas a região de interesse, obtendo-se um modelo tridimensional da aorta infra-renal e artérias ilíacas. A partir daí, foi confeccionado um modelo físico com a utilização de prototipagem rápida. Um simulador cardiovascular controlado por computador foi desenvolvido com o intuito de replicar características fisiológicas e patológicas do sistema cardiovascular humano. Esse modelo de aneurisma foi utilizado para simulação em bancada experimental, onde é possível reproduzir alguns parâmetros como pressão, fluxo, temperatura, resistência e complacência vascular. Também foi gerado um modelo computacional onde os parâmetros obtidos na simulação in vitro foram utilizados como condição de contorno inicial para o estudo computacional. Foram adotados padrões normotenso e hipertenso, e os resultados computacionais e experimentais foram analisados e comparados. O trabalho propõe uma metodologia que possibilite a obtenção de dados anatômicos e hemodinâmicos relativos ao segmento arterial acometido pela afecção, com o objetivo de fornecer informações adicionais no diagnóstico do aneurisma de aorta. / Abdominal Aortic Aneurysm (AAA) is defined as a focal and permanent dilatation of the arterial wall, most often occurring in between the renal and iliac arteries, as consequence of arterial wall weakness or because of an abnormal solicitation of that normal structure. This disease primarily affects elderly population over 65 years of age, and the most important risk factors are smoking, hypertension, family history and chronic obstructive pulmonary disease. In the last years, the prevalence is rising up almost twice the diagnosed cases in the United States (Bonamigo and Von Ristow, 1999). Nowadays, AAA is the thirtieth cause of death in the United States, in the elderly masculine population over 65 years of age, and in case of ruptured aneurysm, it is the third cause of sudden death in the United States. The overall mortality rate is about 80% in countries with systematic and compulsory evaluation of death cause. This is due to the fact that substantial intra-abdominal hemorrhage is often accompanied by delays in transport and diagnoses, and the need for emergency surgery in elderly patients that frequently have significant renal and cardiopulmonary comorbidity. It is suggested that the formation and expansion of the AAA are accompanied by wall stress increasing and / or decreasing in the tissue capacity to withstand this stress. The rupture occurs when the wall stress exceed the stress the tissue can accept. The risk of rupture increases with aneurysm expansion, wall stress increasing and it is exacerbated when associated with arterial hypertension. In the present work, morphological data from thoracic region of the patient was acquired by using multi-slice CT (Computed Tomography). These DICOM images had been treated to select only the interest region, getting a three-dimensional infra-renal aortic and iliac model. Then, it was made a physical model by using rapid prototyping. This model was used for in vitro experimentation in a computer controlled mock system, in which it is possible to replicate physiological and pathological characteristics of human being cardiovascular system. Some parameters such as pressure, flow, temperature, vascular resistance and compliance can be reproduced by the use of a mock circulatory system. These parameters were used as initial boundary conditions in order to calibrate a computational model. It was adopted normotensive and hypertensive patterns and computational and experimental results were analyzed and compared. The paper proposes a methodology which allows the acquisition of anatomical and hemodynamic data on the vessel segment affected by the pathology, with the goal of providing additional information in the diagnosis of aortic aneurysm.

Introdução: A alta incidência de oclusão incompleta e recanalização dos aneurismas intracranianos de colo largo tratados por via endovascular levaram ao desenvolvimento de novas técnicas, entre elas o uso do Onyx ®. Objetivos: avaliar a eficiência do agente embólico líquido Onyx® em produzir oclusão completa dos aneurismas intracranianos de colo largo e avaliar a estabilidade do tratamento aos 6 meses e aos 18 meses, por meio de controles angiográficos. Casuística e métodos: Esta tese foi realizada na Seção de Neuroradiologia Intervencionista da Med Imagem, do Hospital São Joaquim da Real e Benemérita Associação Portuguesa de Beneficência de São Paulo, através da revisão de dados clínicos e radiológicos de 69 pacientes tratados pelo autor, com 84 aneurismas intracranianos de colo largo no período de julho de 2002 a fevereiro de 2006. Dez pacientes eram do sexo masculino e 59 do sexo feminino, com idade variando de 24 anos a 86 anos (mediana de 52 anos). Todos os aneurismas tinham origem lateral à artéria e apresentavam pelo menos um dos critérios usados para definir colo largo - colo maior que 4 mm de diâmetro e relação saco/colo menor que 1,5. Cinqüenta aneurismas eram pequenos, 30 grandes e quatro gigantes (diâmetro máximo menor que 12mm, de 12mm a 25mm e maiores que 25mm, respectivamente). As apresentações clínicas mais comuns foram: achado incidental em 34 pacientes, pós-hemorragia sub aracnóide e recanalização após tratamento com espirais destacáveis em 10. A maioria dos aneurismas era da artéria carótida interna (76 aneurismas). Controles angiográficos foram feitos ao final, aos seis meses e aos 18 meses do tratamento (controles I, II e III respectivamente), sendo analisados principalmente o grau de oclusão (completa ou incompleta), incidência de recanalização e complicações clínicas. Avaliação estatística foi feita pelo método de Kaplan-Meier para o percentual cumulativo de oclusão completa e percentual de recanalização e análise univariada e multivariada dos fatores preditivos de oclusão total imediata e tardia através de regressão logística. Resultados: O índice de oclusão completa foi de 65,5%, 84,6% e de 90,3% para todos os aneurismas, nos controles I, II e III respectivamente. Estes índices foram de 74%, 95,1% e de 95,2% para os aneurismas pequenos e de 53,3%, 70% e de 80% para os aneurismas grandes nos controles I, II e III respectivamente. Oclusão completa ocorreu em 50% dos aneurismas gigantes nos controles I e II, sem haver controle III neste grupo. Recanalização ocorreu em 3 aneurismas (4,6%). O porcentual cumulativo de oclusão completa foi de 97,63% (IC de 95% variando de 95,27 a 100) para os aneurismas pequenos aos 9 meses e de 83,86% (IC de 95% variando de 67,73 a 100) para os aneurismas grandes aos 21 meses. Três pacientes faleceram (4,3%), havendo relação com o procedimento em dois (2,9%). Morbidade permanente ocorreu em cinco pacientes (7,2%), sendo incapacitante em um (1,4%). Conclusões: 1. O uso do Onyx® foi eficiente na oclusão completa dos aneurismas intracranianos de colo largo. 2. O tratamento foi estável nos controles angiográficos aos 6 meses e aos 18 meses. / Introduction: The high rate of incomplete occlusion and intracranial large neck aneurysms recanalization lead to the development of new techniques, including the use of Onyx®. Purpose: to evaluate the efficacy of the liquid embolic system Onyx ® to produce completes occlusion of the intracranial large neck aneurysms and evaluates the stability of the treatment at 6 month and 18 month angiographic control. Materials and Methods: this thesis has been performed at Section of Interventional Neuroradiology of Med Imagem, at the Hospital São Joaquim da Real e Benemérita Associação Portuguesa de Beneficência de São Paulo, based on a review of clinical and radiological records of 69 patients treated by the author, harboring 84 large neck intracranial aneurysms between July 2002 and February 2006. Ten patients were male and 59 female, with age ranging from 24 to 86 years old. All aneurysms were lateral to the parent vessel and were wide neck (neck > 4 mm and/or domus to neck ratio < 1.5). Fifty aneurysms were small (<12 mm), 30 were large (12 to 25 mm) and 4 were giant (> 25 mm). Thirty four aneurysms were incidental, 10 were ruptured and 10 were recanalized after coil treatment and the majority was located in the internal carotid artery (76). Angiographic follow-up was done at the end of the procedure, at six month and at 18 month (controls I, II and III respectively), analyzing the rate of complete occlusion, recanalization and clinical complication. Statically analysis were done by Kaplan-Meier method for cumulative percentage of complete aneurysm occlusion and for recanalization, and univariate and multivariate analysis of predictive factors of immediate and late complete occlusion through logistic regression. Results: Complete aneurysm occlusion was achieved in 65.5% on immediate control, in 84.6% at 6 month, and in 90.3% at 18 month follow-up periods for all aneurysms. This rate was 74%, 95.1% and 95.2% for small and 53.3%, 70% and 80% for large aneurysms at the same follow-up periods. In the giant aneurysm group, two had complete and stable occlusion at six month follow-up angiography. Recanalization was seen in three aneurysms (4,6%). Kaplan Meyer\'s cumulative percentage of complete aneurysm occlusion was 97.63% (CI 95% ranging from 95,27 to 100) for small aneurysms at 9 months and 83.86% (CI 95% ranging from 67,73 to 100) for large aneurysms at 21 months. There were three deaths (4,3%), two procedure-related (2.9%). Overall morbidity was 7.2%, being disabling in one (1,4%). Conclusions: 1. The use of Onyx was efficient in the complete occlusion of wide neck intracranial aneurysms. 2. The treatment was stable at 6 month and 18 month angiographic controls.

<p>Accurately assessing the risk and growth of rupture among intracranial aneurysms (IA) remains a challenging task for clinicians. Hemodynamic factors are known to play a critical role in the development of IAs, but the specific mechanisms are not well understood. Many studies have sought to correlate specific flow metrics to risk of growth and rupture but have reported conflicting findings. Computational fluid dynamics (CFD) has predominantly been the methodology used to study IA hemodynamics. Yet, CFD assumptions and limitations coupled with the lack of CFD validation has precluded clinical acceptance of IA hemodynamic assessments and likely contributed to the contradictory results among previous studies. Experimental particle image velocimetry (PIV) studies have been noticeably limited in both scope and number among IA studies, in part due to the complexity associated with such experiments. Moreover, the limited understanding of the robustness of hemodynamic metrics across varying flow and measurement environments and the effect of transitional flow in IAs also remain open issues. In this work, techniques to enhance IA PIV capabilities were developed and the first volumetric pulsatile IA PIV study was performed. A novel blood analog solution—a mixture of water, glycerol and urea— was developed and an autonomous methodology for reducing experimental noise in velocity fields was introduced and demonstrated. Both of these experimental techniques can also be used in PIV studies extending beyond IA applications. Further, the onset and development of transitional flow in physiological, pulsatile waveforms was explored. The robustness of hemodynamic metrics such as wall shear stress, oscillatory shear index, and relative residence time across varying modalities, spatiotemporal resolutions, and flow assumptions was explored. Additional hemodynamic metrics which have been demonstrated to be influential in other cardiovascular flows but yet to be tested in IA studies were also identified and considered. Ultimately this work provides a framework for future IA PIV studies as well as insight on using hemodynamic evaluations to assess the risk of growth and rupture of an IA, thereby taking steps towards enhancing the clinical utility of such analysis.</p>

<p>By applying a segmentation procedure to two different sets of computed tomography scans, two geometrical models of the abdominal aorta, containing one inlet and two outlets have been constructed. One of these depicts a healthy blood vessel while the other displays one afflicted with a Abdominal Aortic Aneurysm. </p><p>After inputting these geometries into the computational dynamics software FLUENT, six simulations of laminar, stationary flow of a fluid that was assumed to be Newtonian were performed. The mass flow rate across the model outlet boundaries was varied for the different simulations to produce a basis for a parameter analysis study. </p><p>The segmentation data was also used as input data to a surface description procedure which produced not only the surface itself, but also the first and second directional derivatives in every one of its defining spatial data points. These sets of derivatives were followingly applied in an additional procedure that calculated values of Gaussian curvature. </p><p>A parameter variance analysis was carried out to evaluate the performance of the surface generation procedure. An array of resultant surfaces and surface directional derivatives were obtained. Values of Gaussian curvature were calculated in the defining spatial data points of a few selected surfaces. </p><p>The curvature values of a selected data set were visualized through a contour plot as well as through a surface map. Comparisons between the curvature surface map and one wall shear stress surface map were made.</p>

Chlamydophila pneumoniae (C. pneumoniae) has been suggested as a stimulator of chronic inflammation in atherosclerosis. C. pneumoniae DNA was demonstrated in aortic biopsies in 50% of patients with stable angina pectoris or acute coronary syndrome undergoing coronary artery bypass grafting. C. pneumoniae mRNA, a marker of replicating bacteria, was demonstrated in 18% of the aortic biopsies. Inflammation may have a role in the pathogenesis of thoracic aortic aneurysm, aortic dissection and aortic valve stenosis. C. pneumoniae DNA was demonstrated in aortic biopsies in 26% of thoracic aortic aneurysm patients and in 11% of aortic dissection patients undergoing thoracic surgery and in 22% of stenotic aortic heart valves from patients undergoing aortic valve replacement. No bacterial mRNA was demonstrated in these aortic biopsies, nor in the valves, suggesting that the infection has passed into a persistent state. C. pneumoniae DNA was demonstrated in peripheral blood mononuclear cells in only 5% of aortic valve stenosis patients and not in thoracic aortic aneurysm or aortic dissection patients, suggesting that the bacterium disseminated to the cardiovascular tissue long before the patient required surgery. The copper/zinc ratio in serum, a marker of infection/inflammation, was significantly elevated in thoracic aortic aneurysm patients, supporting an inflammatory pathogenesis. Patients positive for C. pneumoniae in the aortic valve had more advanced coronary atherosclerosis, further supporting a possible role for C. pneumoniae in atherosclerosis. Mice were infected with C. pneumoniae that disseminated to all organs investigated (i.e. lungs, heart, aorta, liver and spleen). Trace element concentrations were altered in infected animals with an increased copper/zinc ratio in serum, a progressively increased iron concentration in the liver and a progressively decreased iron concentration in serum. Iron is important for C. pneumoniae metabolism, and a changed iron homeostasis was noted in infected mice by alterations in iron-regulating proteins, such as DMT1 and hepcidin.