O Proepicárdio (PE) é uma estrutura transitória que dá origem aos componentes dos vasos coronários. Para avaliar seu potencial vascular em sítio adulto, transplantamos um coração neonatal para o pavilhão auricular de um animal adulto. Duas semanas depois, 2 PEs de embriões GFP+ foram transferidos para a superfície deste coração. Em outro grupo, transferimos os PEs diretamente para o pavilhão auricular. Para avaliar a incorporação de células GFP, e investigar sua diferenciação realizamos ensaios de imunofluorescência (IF) para GFP em combinação com outros marcadores. A adição do PE em sítio adulto teve como resultado a participação deste em processos de vasculogênese, iniciando a formação de novos vasos sanguíneos via formação de ilhotas sanguíneas e em um processo angiogênico, diferenciando-se em células endoteliais que se incorporaram aos vasos já existentes. Baseados nisso podemos afirmar que o PE possui potencial vasculogênico/angiogênico em sítio adulto, podendo ser exploradas como modelo para revascularização cardíaca e recuperação de tecidos vasculares. / The Proepicárdio (PE) is a transient structure giving rise to all components of the coronary vessels. To evaluate the vasculogenic potential of the PE in an adult site, a neonatal heart was transplanted into the subcutaneous of an adult ear Later, two PE from GFP-transgenic mice were transferred to the surface of this heart. In another group, we transferred the PEs directly into the ear pinna. To evaluate the incorporation of GFP cells derived from the PE, and to investigate their possible differentiation, we performed immunofluorescence (IF) for GFP in combination with other markers. The addition of PE in an adult site resulted in its participation in a vasculogenic and in an angiogenic processes. Based on this we conclude that PE cells can differentiate and likely participate in a neovascularization process when transplanted to adult sites. These findings demonstrate that the vasculogenic potential of the PE cells is conserved in an adult site and our model is adequate to study the mechanisms involved in the development and regeneration of vasculature.

Introdução: Segmentos coronários com doença aterosclerótica manifesta podem coexistir no mesmo paciente com artérias normais à angiografia. Porém as características desses vasos angiograficamente normais permanecem pouco estudadas. O presente estudo visa a descrição in vivo, através do ultrassom intravascular com histologia virtual, da presença, grau de acometimento e composição da doença coronária aterosclerótica em artérias normais ou quase normais (irregularidades parietais) do ponto de vista angiográfico, em pacientes com doença coronária obstrutiva em outros territórios. Métodos: Pacientes com doença coronária obstrutiva foram selecionados de forma prospectiva e foram submetidos a estudo ultrassonográfico com histologia virtual de múltiplos vasos. Artérias epicárdicas principais foram classificadas em quatro grupos baseado na sua aparência angiográfica: 1) vasos completamente normais, 2) vasos com irregularidades parietais, 3) vasos com pelo menos uma estenose discreta, 4) vasos com pelo menos uma estenose moderada ou importante. Para os vasos com estenoses luminais (grupos 3 e 4 acima), apenas segmentos que não possuíam lesão maior ou igual a 30% (não obstrutivos) foram incluídos na análise. Resultados: Um total de 60 pacientes (154 vasos) foram incluídos no estudo. Vasos angiograficamente normais apresentaram menor carga de placa, menos componente necrótico, menor densidade de lesões e quase nenhuma placa com características de alto risco. Entretanto, em vasos com irregularidades parietais encontramos uma maior carga de placa com elevada densidade de lesões pelo ultrassom intravascular similar a segmentos \"não obstrutivos\" de vasos com estenoses luminais evidentes pela angiografia em outro ponto. Conclusão: Artérias coronárias completamente normais pela angiografia parecem apresentar pouca doença aterosclerótica. Entretanto, vasos com irregularidades parietais estão associados com um maior acometimento aterosclerótico e elevada densidade placas de alto risco, achado este que não pode ser rapidamente obtido com o uso apenas da angiografia coronária / Background: Extensively diseased arteries may co-exist, in the same patient, with coronary vessels with a normal appearance by angiography. Thus far, however, the characteristics of the latter remain poorly described. The present study aims to evaluate in vivo, using intravascular ultrasound (IVUS) with radiofrequency backscatter analysis (RF), the presence, degree, and composition of atherosclerosis in arteries with angiographically normal or near-normal appearance, in patients with diagnosed coronary disease in other territories. Methods: Patients with diagnosed obstructive coronary disease were prospectively selected and underwent protocol-mandated multi-vessel IVUS-RF. Major epicardial branches were classified into four groups based on their angiographic appearance: 1) completely normal-looking; 2) near-normal; 3) at least one mild stenosis; 4) at least one severe or moderate stenosis. For vessels with lumen stenosis (groups 3 and 4 above), only \"non-stenotic\" portions were included in the IVUS analysis. Results: A total of 60 patients (154 vessels) comprised the study population. Completely normal-looking vessels had lower plaque burden, lower necrotic component, lower density of lesions, and almost null high-risk plaques. Conversely, a nearnormal aspect, with only subtle lumen irregularities by angiography, was associated with increased disease burden, with an elevated density of plaques with high-risk features, similar to \"non-stenotic\" portions of vessels with obvious atherosclerosis elsewhere. Conclusions: Coronary vessels with a completely normal-looking appearance by angiography appear to have little atherosclerosis. Conversely, yet mild luminal irregularities by angiography are associated with increased disease burden and elevated density of high-risk plaques by IVUS, which cannot be readily assessable by angiography alone. Descriptors: angiography; atherosclerosis; coronary artery disease; plaque, atherosclerotic; ultrasonography, interventional; coronary vessels.Background: Extensively diseased arteries may co-exist, in the same patient, with coronary vessels with a normal appearance by angiography. Thus far, however, the characteristics of the latter remain poorly described. The present study aims to evaluate in vivo, using intravascular ultrasound (IVUS) with radiofrequency backscatter analysis (RF), the presence, degree, and composition of atherosclerosis in arteries with angiographically normal or near-normal appearance, in patients with diagnosed coronary disease in other territories. Methods: Patients with diagnosed obstructive coronary disease were prospectively selected and underwent protocol-mandated multi-vessel IVUS-RF. Major epicardial branches were classified into four groups based on their angiographic appearance: 1) completely normal-looking; 2) near-normal; 3) at least one mild stenosis; 4) at least one severe or moderate stenosis. For vessels with lumen stenosis (groups 3 and 4 above), only \"non-stenotic\" portions were included in the IVUS analysis. Results: A total of 60 patients (154 vessels) comprised the study population. Completely normal-looking vessels had lower plaque burden, lower necrotic component, lower density of lesions, and almost null high-risk plaques. Conversely, a nearnormal aspect, with only subtle lumen irregularities by angiography, was associated with increased disease burden, with an elevated density of plaques with high-risk features, similar to \"non-stenotic\" portions of vessels with obvious atherosclerosis elsewhere. Conclusions: Coronary vessels with a completely normal-looking appearance by angiography appear to have little atherosclerosis. Conversely, yet mild luminal irregularities by angiography are associated with increased disease burden and elevated density of high-risk plaques by IVUS, which cannot be readily assessable by angiography alone

INTRODUÇÃO: A avaliação da morfologia das artérias coronárias é objeto de interesse dentro do desenvolvimento de uma melhor qualidade de imagem que possibilite um diagnóstico fidedigno das lesões coronárias. Para isso, estudos com ressonância magnética (RM) e ultra-som intravascular coronário (UIV) tem se desenvolvido na tentativa de mensurar e caracterizar melhor a doença coronária in vivo. OBJETIVO: Determinar a capacidade da ressonância magnética em detectar alterações na luz e na parede das artérias coronárias com aterosclerose, tendo como padrões o ultra-som intracoronário e a anatomia patológica.MÉTODOS: Estudamos 13 corações de pacientes, falecidos por infarto do miocárdio. Os corações foram fixados com solução de formol a 10% sob perfusão com pressão constante de 80 mmHg. Em seguida as artérias coronárias interventricular anterior, direita e circunflexa esquerda foram dissecadas, preservando-se a adventícia e parte da aorta. As seguintes medidas foram feitas: área total do vaso (ATV), área da luz (AL), maior (MaDV) e menor (MeDV) diâmetro do vaso, diâmetro mínimo (DminL) e máximo (DmaxL) da luz do vaso e espessura mínima (EminP) e máxima (EMaxP) da parede pelos seguintes métodos: UIV, RM e anatomia patológica (AP). Foram analisadas 38 artérias, correspondendo a 355 segmentos arteriais. Utilizamos em média os 3 primeiros centímetros de cada artéria, e em cada centímetro foram avaliados 3 segmentos: proximal, médio e distal. As medidas obtidas nos 3 métodos foram comparadas através do teste de correlação de Pearson e método de Bland Altman Plot. As comparações entre os 3 métodos, pelas suas respectivas médias e desvios padrão, foram realizadas pela análise de variância para medidas repetidas.RESULTADOS: As médias das variáveis na RM,UIV e AP foram respectivamente: ATV 15,46 ± 4,83, 13,86 ± 5,20 e 11,87 ± 4,57; MaDV 4,75 ± 0,84, 4,40 ± 0,87 e 4,18 ± 0,87; MeDV 4,23 ± 0,73, 3,75 ± 0,72 e 3,48 ± 0,70; AL 5,59 ± 2,93, 6,86 ± 3,18 e 5,57 ± 2,46; DmiL 2,54 ± 0,64, 2,55 ± 0,57 e 2,32 ± 0,52; DmaxL 3,07 ± 0,65, 3,34 ± 0,76 e 3,04 ± 0,83; EminP 0,76 ± 0,25, 0,38 ± 0,18 e 0,34 ± 0,17; EmaxP 1,11 ± 0,39, 0,88 ± 0,37 e 0,90 ± 0,48. As correlações com maior significância foram: 1. APxRM: ATV e AL (r=0,767 e r=0,805); 2. RMxUIV ATV e AL (r=0,836 e r=0,770); 3. APxUIV ATV e MeDV (r=0,89 e r=0,692). As variáveis que tiveram melhor correlação foram a ATV, MaDV, MeDV e AL nos 3 métodos. A EminP e EmaxP tiveram fraca correlação. As médias das variáveis DminL e DmáxL nos 3 métodos foram muito próximas. Na variável ATV notamos que a média superestimou a medida do vaso. CONCLUSÃO: A RM correlacionou-se com o UIV para a maioria das medidas, em especial: ATV, MaDV, MeDV, AL e DmaxL. As medidas nesses 2 métodos se correlacionaram em menor intensidade com a AP, sendo nesta sempre com valores menores. Assim, a RM pode vir a ser método fidedigno para o diagnóstico e prognóstico na doença aterosclerótica coronariana, na dependência do desenvolvimento tecnológico permitindo maior rapidez na aquisição de imagens / INTRODUCTION: Numerous studies in the area of image have been conducted to evaluate the morphology of the coronary arteries. Major technical advances have provided better image quality that allows a reliable diagnosis of coronary lesions. For this, studies with cardiovascular magnetic resonance (CMR) and coronary intravascular ultrasound has been developed in an attempt to better measure and characterize coronary heart disease \"in vivo\". PURPOSE: To determine the capacity of CMR to detect changes in the lumen and the wall of the coronary arteries caused by atherosclerosis, using as references intravascular ultrasound (IVUS) and pathology measurements. METHODS: We examined 13 hearts of patients that died of myocardial infarction. The hearts were fixed with formalin solution to the 10% with constant pressure of 80 mmHg. Then the left anterior descending (LAD), left circumflex (LCx) and right coronary (RCA) arteries were dissected from the the aorta and epicardial fat and isolated as pathological specimens. The arteries were analyzed by CMR, IVUS and pathology and the images were subjected to analysis of the following parameters: total vessel area (TVA), lumen area (LA), major (MaVD) and minor vessel diameter (MiVD), minor (MiLD) and major lumen diameter (MaLD), minor (MiWT) and major wall thickness (MaWT). We analyzed the entire 355 arterial segments, using at least the first proximal 2 cm, in most cases 3 cm or more of each artery. In every centimeter we measured the parameters of the proximal, mid and distal segments. The measures obtained in the three methods were compared using Pearson correlation and the method of Bland and Altman plot. Comparisons among the three methods, by their respective averages and standard deviations, were carried out by analysis of variance with repeated measures. RESULTS: Measures in CMR,IVUS e PA were as follow respectively: TVA 15.46 ± 4.83, 13.86 ± 5.20 and 11.87 ± 4.57; MaVD 4.75 ± 0.84, 4.40 ± 0.87 and 4.18 ± 0.87; MeVD 4.23 ± 0.73, 3.75 ± 0.72 and 3.48 ± 0.70; LA 5.59 ± 2.93, 6.86 ± 3.18 and 5.57 ± 2.46; MiLD 2.54 ± 0.64, 2.55 ± 0.57 and 2.32 ± 0.52; MaLD 3.07 ± 0.65, 3.34 ± 0.76 and 3.04 ± 0.83; MiWT 0.76 ± 0.25, 0.38 ± 0.18 and 0.34 ± 0.17; MaWT 1.11 ± 0.39, 0.88 ± 0.37 and 0.90 ± 0.48.The best correlations were: 1. PAxCMR: TVA and LA (r=0.767 and r=0.805); 2. CMRxIVUS: TVA and LA (r=0.836 and r=0.770); 3. PAxIVUS: TVA and MiVD (r=0.89 and r=0.692). The variables that have shown the best correlations were TVA, MaVD, MiVD and LA in the 3 methods. The MiWT and MaWT had a weak correlation. The averages of variables MiLD and MaLD in the 3 three methods were very similar. CONCLUSION: CMR correlated well with IVUS for the majority of measures done and in especial for TVA, LA, MaVD, MiVD and MaLD. Measures in both methods had lower correlation with pathology that showed the lower values of all. As a perspective CMR may be a reliable method for measuring coronary artery dimensions, depending on new technical development for faster image acquirer

Coronary vessel development is a crucial part of heart development requiring the interplay of the epicardial, myocardial and endocardial layers of the heart for proper formation. Coronary vascularization is regulated by a host of transcription factors further regulated by chromatin remodeling enzymes, including Histone Deacetylases (HDACs). To investigate the functions of HDACs in coronary vascular development, we have deleted Hdac3 in endocardial cells using Cre LoxP technology. Endocardial cell-­‐specific deletion of Hdac3 results in aberrant coronary vessel formation and complete postnatal lethality. We have thus shown that Hdac3 is a critical regulator of the coronary vascular development pathway.

Introdução: A doença arterial coronária (DAC) é avaliada através dos aspectos anatômicos da placa aterosclerótica ou a partir da repercussão funcional da estenose, por métodos diagnósticos diversos. O ultrassom intravascular (IVUS) fornece uma avaliação anatômica precisa do lúmen e da parede do vaso, tendo sido validado como uma ferramenta útil para guiar a intervenção coronária percutânea (ICP). No entanto, do ponto de vista diagnóstico, o IVUS representa mal o estado funcional (isto é, informação relacionada ao comprometimento de fluxo) do vaso interrogado. A reserva de fluxo fracionada (FFR) é método importante para identificação de isquemia, discriminando as estenoses coronárias que podem se beneficiar de ICP. Objetivamos desenvolver e avaliar o desempenho diagnóstico de um novo algoritmo computacional para estimar a FFR à partir das imagens do IVUS tridimensional (IVUSFR), comparando-o com o método padrão ouro para estimação de fluxo coronário invasivo (FFRPW). Métodos: Pacientes com DAC estável conhecida ou suspeita encaminhados para cateterismo cardíaco eletivo foram submetidos a avaliação complementar com medida de fluxo coronário pelo FFRPW e com imagem intravascular pelo IVUS, no mesmo procedimento, a fim de avaliar lesões intermediárias. As imagens do IVUS foram processadas para gerar uma malha computacional tridimensional que condensa as características geométricas do vaso. O IVUSFR foi obtido utilizando dinâmica de fluido computacional, configurando-se as condições de contorno a partir de características específicas do paciente e do território coronário irrigado. As medidas de FFRPW foram dicotomizadas no limiar de 0,80 para definir lesões hemodinamicamente significativas e avaliar o desempenho diagnóstico do IVUSFR. Resultados: Um total de 34 artérias coronárias de 24 pacientes foi analisado. A área luminal mínima média avaliada pelo IVUS de 4,14 ± 1,74 mm2, e carga de placa média de 66±10% caracterizam o grau intermediário das lesões. O IVUSFR correlacionou significativamente (r = 0,79; p < 0,001) e mostrou boa concordância com a FFRPW, apresentando diferença média de -0,008 ± 0,067 (p = 0,47). O IVUSFR apresentou acurácia, sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo de 91%, 89%, 92%, 80% e 96%, respectivamente, para detectar estenoses hemodinamicamente significativas. Conclusão: O processamento computacional do IVUSFR é um novo método que permite a avaliação funcional da estenose coronária intermediária de forma acurada, enriquecendo as informações anatômicas do IVUS / Introduction: Coronary artery disease (CAD) is assessed through the anatomical aspects of the atherosclerotic plaque or through the functional impairment of the stenosis, by different diagnostic methods. Intravascular ultrasound (IVUS) provides accurate anatomic assessment of lumen and vessel wall and has been validated as a useful tool to guide percutaneous coronary intervention (PCI). However, from the diagnostic point of view, IVUS poorly represents the functional status (i.e. flow-related information) of the imaged vessel. Fractional flow reserve (FFR) is an important tool to identify ischemia, discriminating coronary stenosis that may benefit from PCI. We aimed to develop and evaluate the diagnostic performance of a novel computational algorithm based on three-dimensional IVUS imaging in estimating fractional flow reserve (IVUSFR), compared to gold-standard invasive measurements (FFRPW). Methods: Patients with known or suspected stable coronary disease scheduled for elective cardiac catheterization underwent FFRPW measurement and IVUS imaging in the same procedure to evaluate intermediate lesions. A processing methodology was applied on IVUS to generate a computational mesh condensing the geometric characteristics of the vessel. Through computational fluid dynamics, IVUSFR was obtained from patient-level morphological definition of arterial districts and from territory-specific boundary conditions. FFRPW measurements were dichotomized at the 0.80 thresholds to define hemodynamically significant lesions and evaluate diagnostic performance of IVUSFR. Results: A total of 24 patients with 34 vessels were analyzed. The mean minimum luminal area assessed by IVUS was 4.14 ± 1.74 mm2, and mean plaque burden was 66 ± 10%, characterizing intermediate lesions. IVUSFR significantly correlated (r = 0.79; p < 0.001) and showed good agreement with FFRPW, with a mean difference of -0.008 ± 0.067 (p = 0.47). IVUSFR presented an overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 91%, 89%, 92%, 80%, and 96% respectively to detect significant stenosis. Conclusion: The computational processing of IVUSFR is a new method that allows the evaluation of the functional significance of coronary stenosis in an accurate way, enriching the anatomical information of IVUS

Introdução: A doença arterial coronária (DAC) é avaliada através dos aspectos anatômicos da placa aterosclerótica ou a partir da repercussão funcional da estenose, por métodos diagnósticos diversos. O ultrassom intravascular (IVUS) fornece uma avaliação anatômica precisa do lúmen e da parede do vaso, tendo sido validado como uma ferramenta útil para guiar a intervenção coronária percutânea (ICP). No entanto, do ponto de vista diagnóstico, o IVUS representa mal o estado funcional (isto é, informação relacionada ao comprometimento de fluxo) do vaso interrogado. A reserva de fluxo fracionada (FFR) é método importante para identificação de isquemia, discriminando as estenoses coronárias que podem se beneficiar de ICP. Objetivamos desenvolver e avaliar o desempenho diagnóstico de um novo algoritmo computacional para estimar a FFR à partir das imagens do IVUS tridimensional (IVUSFR), comparando-o com o método padrão ouro para estimação de fluxo coronário invasivo (FFRPW). Métodos: Pacientes com DAC estável conhecida ou suspeita encaminhados para cateterismo cardíaco eletivo foram submetidos a avaliação complementar com medida de fluxo coronário pelo FFRPW e com imagem intravascular pelo IVUS, no mesmo procedimento, a fim de avaliar lesões intermediárias. As imagens do IVUS foram processadas para gerar uma malha computacional tridimensional que condensa as características geométricas do vaso. O IVUSFR foi obtido utilizando dinâmica de fluido computacional, configurando-se as condições de contorno a partir de características específicas do paciente e do território coronário irrigado. As medidas de FFRPW foram dicotomizadas no limiar de 0,80 para definir lesões hemodinamicamente significativas e avaliar o desempenho diagnóstico do IVUSFR. Resultados: Um total de 34 artérias coronárias de 24 pacientes foi analisado. A área luminal mínima média avaliada pelo IVUS de 4,14 ± 1,74 mm2, e carga de placa média de 66±10% caracterizam o grau intermediário das lesões. O IVUSFR correlacionou significativamente (r = 0,79; p < 0,001) e mostrou boa concordância com a FFRPW, apresentando diferença média de -0,008 ± 0,067 (p = 0,47). O IVUSFR apresentou acurácia, sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo de 91%, 89%, 92%, 80% e 96%, respectivamente, para detectar estenoses hemodinamicamente significativas. Conclusão: O processamento computacional do IVUSFR é um novo método que permite a avaliação funcional da estenose coronária intermediária de forma acurada, enriquecendo as informações anatômicas do IVUS / Introduction: Coronary artery disease (CAD) is assessed through the anatomical aspects of the atherosclerotic plaque or through the functional impairment of the stenosis, by different diagnostic methods. Intravascular ultrasound (IVUS) provides accurate anatomic assessment of lumen and vessel wall and has been validated as a useful tool to guide percutaneous coronary intervention (PCI). However, from the diagnostic point of view, IVUS poorly represents the functional status (i.e. flow-related information) of the imaged vessel. Fractional flow reserve (FFR) is an important tool to identify ischemia, discriminating coronary stenosis that may benefit from PCI. We aimed to develop and evaluate the diagnostic performance of a novel computational algorithm based on three-dimensional IVUS imaging in estimating fractional flow reserve (IVUSFR), compared to gold-standard invasive measurements (FFRPW). Methods: Patients with known or suspected stable coronary disease scheduled for elective cardiac catheterization underwent FFRPW measurement and IVUS imaging in the same procedure to evaluate intermediate lesions. A processing methodology was applied on IVUS to generate a computational mesh condensing the geometric characteristics of the vessel. Through computational fluid dynamics, IVUSFR was obtained from patient-level morphological definition of arterial districts and from territory-specific boundary conditions. FFRPW measurements were dichotomized at the 0.80 thresholds to define hemodynamically significant lesions and evaluate diagnostic performance of IVUSFR. Results: A total of 24 patients with 34 vessels were analyzed. The mean minimum luminal area assessed by IVUS was 4.14 ± 1.74 mm2, and mean plaque burden was 66 ± 10%, characterizing intermediate lesions. IVUSFR significantly correlated (r = 0.79; p < 0.001) and showed good agreement with FFRPW, with a mean difference of -0.008 ± 0.067 (p = 0.47). IVUSFR presented an overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 91%, 89%, 92%, 80%, and 96% respectively to detect significant stenosis. Conclusion: The computational processing of IVUSFR is a new method that allows the evaluation of the functional significance of coronary stenosis in an accurate way, enriching the anatomical information of IVUS

Fundamentos: A caracterização precisa da interação da placa aterosclerótica no momento do implante do stent é crucial para o entendimento da complacência e da cicatrização vasculares. Objetivamos investigar se a composição da placa avaliada pela tomografia de coerência óptica (OCT), influencia as alterações agudas no procedimento índice do implante do stent e na cicatrização vascular no seguimento tardio. Métodos: Os pacientes tratados com um único tipo de stent eluidor de fármaco (cromo cobalto, eluidor de sirolimus e polímero bioabsorvível) foram incluídos prospectivamente, seguindo um protocolo com etapas de dilatações progressivas do vaso. As imagens de OCT sequenciais foram realizadas no procedimento índice (basal e a cada etapa do protocolo) e no seguimento tardio, co-registradas e analisadas a cada 0,6mm. A avaliação semiquantitativa da placa foi realizada dividindo-se secções transversas em 4 quadrantes, com cada quadrante rotulado de acordo com o seu componente mais prevalente (fibrótico, calcificado, lipídico, normal). A interação stent-vaso avaliada pela OCT foi utilizada como indicador substituto para lesão e cicatrização vasculares após o implante do stent. Resultados: Um total de 22 lesões (1stent/lesão) de 20 pacientes e 2298 seções transversas de OCT foram analisadas no procedimento índice. O reestudo com OCT foi realizado em 17 pacientes e 19 lesões (86%). O componente de placa predominante foi fibrótico (fibrótico = 46.84 ± 16%; lipídico = 17.63 ± 10.72%; calcificado = 4.63 ± 5.9%; normal = 29.16 ± 12.24; não analizável=1.74 ± 5.35%). Houve um aumento nas áreas da luz (10atm = 5.5 (4.5 - 7.4) mm2, 14-16atm = 6.0 (4.7 - 7.70) mm2, 20atm = 6.7 (5.5 - 8.2) mm2; P < 0.001) e do stent (10atm = 5.2 (4.3 - 7.0) mm2, 14-16atm = 5.7 (4.5 - 7.5) mm2, 20atm = 6.5 (5.3 - 7.9) mm2; P < 0.001), com um aumento na área do prolapso tecidual (10atm =0.09 (0.06 - 0.12) mm2, 14-16atm =0.10 (0.06 - 0.15) mm2, 20atm =0.15 (0.08 - 0.20) mm2; P < 0.01). Segmentos com muito tecido fibrocalcificado tiveram áreas luminais menores ao longo das etapas da intervenção. Por outro lado, placas com muito conteúdo lipídico ou vaso normal tiveram maiores ganhos nas medidas das áreas luminais mínimas ao longo das dilatações sequenciais. Além disso, placas com muito tecido fibrocalcificado no momento basal apresentaram menor crescimento neointimal no seguimento tardio, enquanto que o grau de conteúdo lipídico e de vaso normal não tiveram impacto sobre a formação do tecido neointimal. Os indicadores substitutos de lesão vascular após o implante do stent correlacionaram-se significativamente com o crescimento neointimal no seguimento tardio. Conclusões: A composição tecidual das placas subjacentes influencia significativamente o comportamento mecânico agudo e a longo prazo dos vasos coronarianos submetidos ao implante de stent. Além disso, a lesão vascular após o implante do stent está potencialmente ligada ao futuro crescimento neointimal no seguimento tardio / Background Accurate characterization of atherosclerotic plaque interaction during stent deployment is crucial to understand vascular compliance and healing. We sought to determine whether plaque composition assessed by optical coherence tomography (OCT), influences acute changes at index procedure and vascular healing at follow up. Methods Patients treated with a single drug-eluting stent type (cobalt chromium with bioabsorbable polymer eluting sirolimus stent) were prospectively included, following a pre-defined step-by-step progressive vessel dilatation. Sequential OCT imaging were performed at the index procedure (baseline and at each time point of the protocol) and at follow up, co-registered and analyzed every 0.6mm for quantitative measurements. Semi-quantitative plaque assessment was performed at baseline by dividing cross-sections into 4 quadrants, with each quadrant labeled according to its most prevalent component (fibrotic, calcific, lipid). OCT assessments of stent-vessel interactions were used as a surrogate for vessel injury and healing after stent implantation. Results A total of 22 lesions (1stent/lesion) of 20 patients and 2298 OCT crosssections were analyzed at the index procedure. For an average of 19.7 months (591.88 ± 60.52 days), 17 of the patients and 19 lesions (86%) underwent OCT imaging at follow up. The predominant percentage plaque component was fibrotic (fibrotic = 46.84 ± 16%; lipid = 17.63 ± 10.72%; calcific = 4.63 ± 5.9%; normal = 29.16 ± 12.24; non-analyzable = 1.74 ± 5.35%). There was an increase in lumen (10atm = 5.5 (4.5 - 7.4) mm2, 14-16atm = 6.0 (4.7 - 7.70) mm2, 20atm = 6.7 (5.5 - 8.2) mm2; P < 0.001) and stent (10atm = 5.2 (4.3 - 7.0) mm2, 14-16atm = 5.7 (4.5 - 7.5) mm2, 20atm = 6.5 (5.3 - 7.9) mm2; P < 0.001) areas, with an increase in tissue prolapse area (10atm =0.09 (0.06 - 0.12) mm2, 14-16atm =0.10 (0.06 - 0.15) mm2, 20atm =0.15 (0.08 - 0.20) mm2; P < 0.01). Segments with high fibrocalcific content tended to have decreased minimal luminal areas along the intervention time-points. Conversely, plaques with high lipid content had increased minimal luminal areas during sequential dilatations. Moreover, plaques with high fibrocalcific tissue at baseline had significantly smaller neointimal growth at follow-up, whereas the degree of lipid content or normal tri-layered vessel had no impact on neointimal formation. OCT surrogates of vessel injury after coronary stenting significantly correlated with neointimal growth at follow-up. Conclusions: Tissue composition of underlying plaques significantly influences the acute mechanical and the long-term behavior of coronary vessels undergoing stent implantation. In addition, vessel injury after coronary stenting is potentially linked to future neointimal growth at follow-up

Os mecanismos envolvidos na associação entre poluição do ar e aumento da mortalidade cardiovascular não estão ao todo esclarecidos. O objetivo deste estudo foi testar os efeitos agudos do PM2.5 da cidade de São Paulo sobre a freqüência cardíaca (FC), variabilidade da freqüência cardíaca (VFC), inflamação sistêmica e vasoconstrição de arteríolas de ratos Wistar saudáveis. O PM2.5 foi coletado em filtros de fibra de vidro utilizando um amostrador de grandes volumes. Para o ECG foram utilizados 47 ratos que foram submetidos a instilação traqueal de: salina, filtro branco, 50 ?g e 100 ?g de PM2.5. A freqüência cardíaca (FC) e o desvio-padrão dos intervalos NN (SDNN) foram avaliados na fase pré, 30 e 60 minutos após a instilação. Outro grupo de 38 ratos foram submetidos a instilação traqueal de: filtro branco, 100 ?g e 500 ?g de PM2.5 para análises hematológicas e histopatológicas. Estes animais foram sacrificados 24 horas após a instilação traqueal para a coleta de sangue e amostras de pulmão e coração para a morfometria e análise da razão peso seco/úmido. A FC diminuiu significativamente (p<0.001) com o tempo, mas não houve efeito de tratamento ou interação entre tempo e tratamento. O SDNN diminuiu 60 minutos após a instilação nos grupos de 50 ?g e 100 ?g de PM2.5 (p=0.025). O número de reticulócitos aumentou significativamente em ambas as doses de PM2.5 (p<0.05), enquanto que o hematócrito aumentou somente no grupo de 500 ?g (p<0.05). Segmentados, neutrófilos e fibrinogênio diminuíram significativamente, enquanto que os linfócitos aumentaram com 100 ?g de PM2.5 (p<0.05). Houve uma diminuição dose-dependente da razão luz/parede (L/P) das arteríolas pulmonares intra-acinares em ambos grupos de PM (p<0.001). A razão L/P das arteríolas peri-bronquiolares diminuiu no grupo que recebeu 500 ?g de PM2.5 (p<0.001). Houve um aumento significativo da razão peso seco/úmido no coração para o grupo que recebeu 500 ?g (p<0.001). Concluindo, as partículas finas da cidade de São Paulo induzem a uma redução do SDNN e promovem alterações histológicas pulmonares e cardíacas, resultando em significante vasoconstrição. A medula óssea também participou na resposta aguda promovida pelas partículas que alcançam os pulmões / The mechanisms involved in the association between air pollution and increased cardiovascular mortality are not fully understood. The objective of this study was to test the acute effects of Sao Paulo PM2.5 on heart rate, heart rate variability, systemic inflammation and vasoconstriction of arterioles of healthy Wistar rats. PM2.5 was collected in glass fiber filters using a high volume sampler. Forty-seven rats were submitted to tracheal instillation with: saline, blank filter, 50 ?g and 100 ?g of PM2.5 to ECG analysis. Heart rate (HR) and standard deviation of the intervals between normal beats (SDNN) were assessed immediately before, 30 and 60 minutes after instillation. Another thirty-eight rats were submitted to tracheal instillation with: blank filter, 100 ?g and 500 ?g of PM2.5 to hematological and histopathological analysis. These animals were sacrificed 24 hours after instillation when blood, heart and lung samples were collected for morphological and wet-to-dry weight ratio analysis. HR decreased significantly (p< 0.001) with time, but no significant effect of treatment or interaction between time and treatment was observed. SDNN decreased 60 minutes after instillation in groups PM2.5 50 ?g and 100 ?g (p=0.025). Reticulocytes significantly increased at both PM2.5 doses (p<0.05) while hematocrit levels increased in the 500 ?g group (p<0.05). Segmented, neutrophils and fibrinogen levels significantly decreased, while lymphocytes increaseded with 100 ?g of PM2.5 (p<0.05). A significant dose-dependent decrease of intra-acinar pulmonary arterioles Lumen/Wall ratio (L/W) was observed in PM groups (p<0.001). Peribronchiolar arterioles L/W showed a significant decrease in the 500?g group (p<0.001). A significant increase in heart wet-to-dry weight ratio was observed in the 500 ?g group (p<0.001). In conclusion, fine particles in the city of Sao Paulo induces a reduction of SDNN and promote pulmonary and cardiac histological alterations, resulting in significant vasoconstriction. In addition, we observed that the bone marrow also participated in the acute response to particles reaching the lungs

Coronary heart diseases (CHD) remain the most prevalent cause of premature death. Ischemic hearts often result from coronary vasculature occlusion. Significant efforts have been made for the treatment of CHD, including medications and surgical procedures. Currently there are still no effective drugs or therapeutics available for the treatment of the disease. Growing new coronary vessels to naturally bypass narrowed/occluded arteries or forming sufficient collaterals to the ischemic region would lead to substantially improved blood perfusion and correction of ischemia. However, this aim remains a theoretical ideal due to the negligible ability to grow new coronary vessels even with current advances in therapeutic angiogenesis. In the present study, we have isolated and identified an active fraction of Geum japonicum (AFGJ) showing significant activity in induction of efficient coronary angiogenesis and heart function improvement. / In addition, proteomics methods were applied to investigate the protein alterations in CHD ischemic hearts and HUVECs. Two dimensional polyacrylamide gel electrophoresis (2-D PAGE) of the heart tissues of CHD rats showed 16 differentially expressed spots compared with sham and vehicle hearts, of which 8 were identified. Furthermore, 11 identified proteins of HUVECs treated with AFGJ or Angio-G at different time points were also observed by 2-D PAGE. The majority of identified proteins was found to be involved in the process of energy metabolisms. / In conclusion, these results have demonstrated therapeutic properties of AFGJ to induce early reconstitution of damaged coronary vasculature through both angiogensis and vasculogenesis. AFGJ treatments may provide a novel therapeutic modality for effective treatment of ischemic heart diseases. / The therapeutic effect of AFGJ on CHD through reconstitution of partially occluded coronary vessels in CHD animal models was demonstrated with underlying signaling mechanisms identified. Briefly, AFGJ could promote the proliferation of human umbilical vein endothelial cells (HUVECs) in vitro and the growth of new blood vessels or coronary collaterals in CHD models after 2-week treatment. The number of newly formed coronary vessels in treated hearts was more than that of vehicle treated hearts, as indicated by both MicroCT and histology analysis. Echocardiography studies demonstrated significant improvement of heart functions 2 weeks after treatment with AFGJ. Furthermore, ECG measurements showed that the altered ST segment in AFGJ treated CHD models almost had full recovery to a normal level while rats in the vehicle group consistently suffered from heart ischemia. Moreover, the results of MicroCT reconstruction directly demonstrated the reconstitution of the damaged coronary vessels with newly formed functional coronary collaterals, as illustrated by more blood vessels density (AFGJ vs vehicle [%]: 4.5+/-0.5 vs 2+/-0.35) and more branching points (AFGJ vs vehicle: 0.94+/-0.07 vs 0.65+/-0.10). These data suggest that AFGJ treatment significantly corrects the ischemia of the affected regions of the heart. / We also explored possible mechanisms underlying the effect of AFGJ. Firstly, AFGJ could induce mesenchymal stem cell (MSC) differentiation into vascular endothelial cells and the differentiated MSCs were involved in the tube formation. Secondly, Angio-G, the component derived from AFGJ, was able to stimulate significant proliferation of HUVECs in a dose dependent manner. Thirdly, in our tube-like capillary formation test of HUVECs in vitro, the length of formed tubes was greatly amplified with increasing concentration of Angio-G. Furthermore, the total length of Angio-G induced tubes was significantly reduced with increasing concentrations of AG490, an inhibitor of JAK/STAT pathways indicating possible involvement of the JAK/STAT signaling pathway. / Chen, Hao. / "December 2009." / Source: Dissertation Abstracts International, Volume: 72-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 136-145). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on April 6, 2010). Vita. Thesis advisor: Mark Milanick "June 2008" Includes bibliographical references