Au cours du vieillissement, les artères cérébrales subissent des modifications structurelles et fonctionnelles, notamment au niveau des cellules musculaires lisses (CML). La CML a pour rôle de maintenir la réactivité vasculaire via une signalisation calcique qui fait intervenir différents acteurs pouvant ainsi réguler deux phénomènes : la contraction et la relaxation. Ces acteurs rassemblent, au sein d’une même cellule, des canaux (CCVD, RYR, IP3R), des pompes calciques (SERCA, PMCA, NCX, STIM/ORAI) et leurs régulateurs (PLB, FKBP12.6, TRPP2, SARAF, TRIC). La restriction calorique (RC), apparaît comme étant un facteur retardant le vieillissement et ses pathologies. Notre travail s’est donc fortement impliqué dans l’étude de la signalisation calcique de la CML, en se focalisant sur les altérations génomiques et fonctionnelles au cours du vieillissement des artères cérébrales chez la souris C57Bl6/j. Nous avons ainsi pu mettre en évidence une altération de la signalisation calcique qui passe en partie par une modulation des niveaux d’expressions génique et protéique des canaux et pompes calciques impliqués dans ce phénomène, et par une modification fonctionnelle en termes de signaux calciques et de contraction. Après 5 mois de régime RC, il a été mis en évidence un ralentissement des altérations de la signalisation calcique liées au vieillissement et une diminution de l’oxydation des CML. / During aging, cerebral arteries undergo structural and functional changes, particularly in smooth muscle cells (SMC). SMC is responsible for maintaining vascular reactivity via calcium signaling involving different actors and can regulate two phenomena: contraction and relaxation. These actors regroup channels (CCVD, RYR, IP3R) calcium pumps (SERCA, PMCA, NCX, STIM / ORAI) and their regulators (PLB, FKBP12.6, TRPP2, SARAF, TRIC). Caloric restriction (CR) appears as a factor in delaying aging and its pathologies. Our work is strongly involved in the study of calcium signaling in SMC, focusing on genomic and functional alterations during aging of cerebral arteries in mice C57BL6/J. We were able to demonstrate an altered calcium signaling, which is partly through modulation of gene and protein expression levels of calcium channels and pumps involved in this phenomenon, and a functional change in terms of calcium signals and contraction. After 5 months under RC, it was highlighted a slow calcium signaling alterations associated with aging and a decrease of SMC oxidation by SAMP8.

O diabetes é uma doença crônica que afeta mais de 8% da população mundial. As alterações vasculares estão relacionadas às principais complicações do diabetes. A aldosterona contribui para a disfunção endotelial após a ativação do receptor mineralocorticóide (MR). Recentemente, foi demonstrado que a aldosterona ativa o receptor de estrógeno acoplado à proteína G (GPER). A ativação de GPER está relacionada a efeitos benéficos na vasculatura. Entretanto, ainda não existem estudos em artérias de resistência relacionando aldosterona e GPER e essa interação no diabetes. Dessa forma, o presente estudo testou a hipótese de que a aldosterona ativando receptores GPER promove efeitos benéficos na vasculatura, mas esses efeitos estão diminuídos no diabetes. Os objetivos foram investigar os níveis de expressão de GPER nos animais controle e db/db [camundongos com mutação no receptor de leptina que desenvolvem obesidade e diabetes tipo 2], quais efeitos da aldosterona são mediados por ativação de GPER e quais mecanismos envolvidos nessa ativação e verificar se estão alterados no diabetes. O grupo diabético apresentou maior expressão de GPER, mas não de MR. A aldosterona promoveu aumento da resposta máxima contrátil à fenilefrina (PE) somente no grupo controle, que foi revertido pelo uso do antagonista de GPER, G15. No grupo diabético, a resposta à PE já é aumentada, o uso dos antagonistas de MR e GPER reduziram a resposta da PE. A aldosterona ainda reduziu a potência de relaxamento da acetilcolina (ACh) em ambos os grupos, por ativação de MR. O antagonismo de GPER por G15 promoveu um redução adicional na potência do relaxamento no grupo controle, mas não afetou a resposta do grupo diabético. Esses achados confirmam a hipótese de que GPER exerce um papel benéfico na vasculatura e esse efeito é perdido no diabetes. Nossos resultados contribuem para a compreensão dos mecanismos que a aldosterona influencia os danos vasculares no diabetes através da ativação de receptores MR e GPER. / Diabetes is a chronic disease that affects more than 8 % of the world population. Vascular changes are related to the major complications of diabetes. Aldosterone contributes to endothelial dysfunction after activation of the mineralocorticoid receptor (MR). It was recently shown that aldosterone also activates the G protein-coupled estrogen receptor (GPER) and induces non genomic effects. The activation of GPER by estrogen or G1 is related to beneficial effects on the vasculature. However, there are no studies demonstrating the relationship between aldosterone and GPER in diabetes mellitus. Therefore, we hypothesized that the beneficial effects of aldosterone mediated by the activation of GPER receptors on vascular reactivity are decreased in diabetes mellitus. Female control and diabetic (db/db) mice [leptin receptor knockout mice that develop obesity and type 2 diabetes] were used. We determined the expression of GPER and the effect of aldosterone in the presence of MR and GPER antagonists in arteries from control and db/db mice and the major signaling pathways involved. The diabetic group showed increased GPER expression, but not MR. In the presence of aldosterone the control increased the maximal contractile response to phenylephrine (PE), and this increase was reversed by the use of GPER antagonist, G15. The response to PE is already increased in the diabetic group. Although aldosterone did not cause further increase the use of MR and GPER antagonists reduced the maximum response to PE at the same level of control. Aldosterone also reduced the potency of acetylcholine (ACh)-induced relaxation in both groups by the activation of MR. GPER antagonism caused further decrease in the potency of ACh-induced relaxation in the control group, while not affecting the response of the diabetic group. These findings confirm the hypothesis that the beneficial effects of aldosterone mediated by the activation of GPER receptors are decreased in diabetes mellitus. Our results contribute to understanding the mechanisms that aldosterone influences the vascular damage in diabetes through activation of MR and GPER receptors.

Introdução: As células do músculo liso vascular (CMLV) são quiescentes nos vasos adultos, com baixa capacidade de migração e de secreção de matriz extracelular, caracterizando fenótipo contrátil. Evidências apontam para a heterogeneidade fenotípica das CMLV ao longo da árvore arterial: há distribuição heterogênea de doenças e de resposta a determinadas drogas nos diferentes vasos, além de variabilidade de expressão dos genes de proteínas contráteis de músculo liso entre eles. O papel das CMLV, em fase adulta, é classicamente descrito como restrito à regulação do tônus de pequenos vasos, sendo insignificante a contribuição da mecânica das CMLV para a complacência das artérias elásticas. Existe a hipótese de que a viscoelasticidade das CMLV contribua para a mecânica final das artérias, sendo o enrijecimento dessas células associado à rigidez arterial. Objetivo: Estudar a variabilidade das propriedades mecânicas e de expressão proteica das CMLV, ao longo da árvore arterial, buscando identificar moduladores regionais para esse fenótipo. Avaliar se situações clínicas sabidamente associadas à rigidez arterial (envelhecimento, sexo feminino pós-menopausa, ancestralidade genética africana, diabetes mellitus e tabagismo) cursam com enrijecimento de CMLV. Métodos: 1) Estudou-se a composição e a organização da camada média de diferentes artérias. As CMLV desses vasos foram avaliadas quanto à viscoelasticidade de citoplasma (G), por meio do ensaio de Citometria Magnético Ótica de Oscilação e, quanto à expressão proteica global, usando cromatografia multidimensional e espectrometria de massas em tandem de alta resolução (Proteômica Shotgun). Os dados mecânicos obtidos foram correlacionados com as características da matriz extracelular (MEC) dos vasos de origem (porcentagem de elastina e quantidade de MEC). Em paralelo, foi realizado experimento de estiramento cíclico (10%/1Hz) das CMLV das diferentes artérias por 24 e 48h, seguido pela mensuração de rigidez de citoplasma. 2) Foram isoladas as CMLV de fragmentos de artéria mamária de 80 pacientes submetidos à cirurgia de revascularização do miocárdio, células essas que foram avaliadas quanto à viscoelasticidade de citoplasma (G, G\' e G\'\'). Elaborou-se modelo estatístico para avaliar se as variáveis clínicas idade, sexo feminino, ancestralidade africana, tabagismo e diabetes mellitus estavam associadas a alterações de mecânica celular. Resultados: 1) A viscoelasticidade das CMLV variou significativamente entre as artérias. As CMLV provenientes de artérias distais (artérias femoral e renal) mostraram-se significativamente mais rígidas que as CMLV de aorta torácica (p < 0,001). Identificou-se correlação negativa entre rigidez de CMLV e quantidade de MEC / elastina na camada média vascular. O regime de estiramento cíclico por 48h reduziu globalmente a rigidez das CMLV. As CMLV provenientes da aorta torácica expressaram maior quantidade de proteínas relacionadas com a estrutura e a organização do citoesqueleto em relação às CMLV da artéria femoral. 2) Constatou-se variabilidade interindividual de viscoelasticidade de CMLV e associação entre tabagismo e sexo feminino com enrijecimento de CMLV. Conclusões: As CMLV são heterogêneas quanto às propriedades mecânicas, à organização do citoesqueleto e à expressão proteica ao longo da árvore arterial, reforçando o conceito de plasticidade fenotípica das CMLV. A mecânica das CMLV é modulada pelas características da MEC e pela tensão circunferencial cíclica aplicada às paredes vasculares pelo fluxo sanguíneo. Mulheres pós-menopausa e tabagistas exibem enrijecimento de CMLV, sendo esse fato um provável contribuinte para a rigidez arterial associada a essas condições e um possível alvo terapêutico a ser avaliado futuramente / Rational: Vascular smooth muscle cells (VSMC) lose their ability to migrate and secrete extracellular matrix (ECM) with the end of vascular development, condition known as contractile phenotype and reversible in the presence of vascular injury. There is evidence of heterogeneity of VSMC phenotype along arterial tree, as the distribution of diseases (atherosclerosis) and the response to drugs vary between different vessels, as well as the expression of smooth muscle-contractile protein genes. The role played by VSMC mechanics on determining large arteries\' compliance was always considered irrelevant. It has been hypothesized that the VSMC mechanical properties are important for vascular mechanics, especially in the pathological scenario, where VSMC stiffening may be associated with arterial rigidity. Goals: Study the variation of VSMC mechanics and protein expression along arterial tree, identifying regional modulators of this phenotype. Evaluate if clinical situations associated with arterial rigidity (ageing, post-menopausal women, African ancestry, diabetes mellitus and smoking) concur with VSMC stiffening. Methods: 1) Different arteries were studied in terms of composition and organization of their media layer. VSMC isolated from these arteries were evaluated regarding cytoplasm viscoelasticity, measured using Optical Magnetic Twisting Cytometry Assay (OMTC), and protein expression, using two-dimensional liquid chromatography and tandem mass spectrometry (Shotgun Proteomics). Mechanical data were correlated with ECM characteristics (percentage of elastin and ECM amount) of the vessels of origin. In parallel, VSMC of different arteries were subjected to cyclic stretching (10%/1Hz) during 24 and 48h, followed by the measurement of their cytoplasm rigidity. 2) VSMC were isolated from fragments of mammary artery of 80 patients subjected to coronary bypass surgery and evaluated regarding their viscoelasticity (G, G\' e G\'\'). A statistic model was elaborated to address if the clinical variables age, female sex, African ancestry, smoking and diabetes mellitus were associated with changes of VSMC mechanics. Results: 1) VSMC viscoelasticity varied significantly amongst the studied arteries. VSMC from heart-distant arteries (femoral and renal arteries) were stiffer than VSMC from thoracic aorta (p < 0,001). There was a negative correlation between VSMC rigidity and the amount of ECM / percentage of elastin within the media layer. 48h-cyclic stretching was associated with a global reduction of VSMC rigidity. VSMC of thoracic aorta expressed significantly more proteins associated with cytoskeleton structure and organization than VSMC of femoral artery. 2) There was a significant inter-individual variation of VSMC viscoelasticity. Smoking and female sex were associated with VSMC stiffening. Conclusion: VSMC mechanics, cytoskeleton organization and protein expression are heterogeneous along arterial tree. VSMC mechanical properties are modulated by ECM characteristics and by regional mechanical forces. This reinforces the concept of phenotypic heterogeneity of VSMC. Post-menopausal women and smokers exhibit stiffer VSMC, representing an important factor for the understanding of the arterial rigidity associated with these conditions and also a possible future therapeutic target

No setor de Vitalidade Fetal na Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo foi conduzido estudo caso-controle com seguimento prospectivo com quarenta e seis pacientes. O objetivo desse estudo foi identificar a associação dos testes de avaliação de vitalidade fetal e acidemia ao nascimento em gestações acometidas com dopplervelocimetria anormal e fluxo diastólico positivo das artérias umbilicais. Da mesma maneira, objetivou-se avaliar a relação entre os resultados antenatais, do parto, e neonatais com a ocorrência de pH fetal inferior a 7,20. A evolução para fluxo diastólico ausente ou reverso durante o seguimento foi critério de exclusão. Os casos foram classificados em dois grupos de acordo com a presença (grupo 1), ou ausência (grupo 2) de acidemia ao nascimento (pH inferior a 7,20), por meio da gasometria arterial de cordão imediatamente após o parto. As seguintes variáveis foram submetidas à análise univariada, comparando-se os grupos 1 e 2: idade materna, síndrome hipertensiva, uso de corticóde antenatal para maturação pulmonar, idade gestacional no momento do parto e testes de avaliação de vitalidade fetal do dia do parto. As modalidades dopplervelocimétricas analisadas foram: índice de pulsatilidade do território arterial (representado pela artéria umbilical e artéria cerebral média) e venoso (índice de pulsatilidade para veias do ducto venoso). Os seguintes parâmetros das atividades biofísicas fetais foram estudados: cardiotocografia (normal e anormal), presença de desaceleração tardia, presença de desaceleração (desaceleração tardia, ou desaceleração variável de mau prognóstico, ou desaceleração prolongada), ausência ou não de movimentos respiratórios, presença ou não de oligoâmnio e classificação do escore do perfil biofísico fetal (normal quando maior que 6, e anormal quando menor ou igual a 6). As variáveis clinicamente relevantes e estatisticamente significativas foram analisadas pela regressão logística. A série compôs-se de 46 pacientes classificadas nos grupos 1 (24 casos) e 2 (22 casos) e as seguintes variáveis foram estatisticamente relacionadas à ocorrência de acidemia no nascimento (p0,05): idade materna, síndrome hipertensiva, cardiotocografia anormal, presença de desaceleração, e ausência de movimentos respiratórios. Na regressão logística, a presença de desaceleração foi preditora de acidemia (p=0,024; OR=8,2; IC95%=1,2-52). Os presentes achados sustentam que a presença de acidemia ao nascimento em fetos com dopplevelocimetria anormal e fluxo diastólico positivo das AU está associada principalmente à anormalidade nos parâmetros agudos da avaliação da vitalidade fetal. A presença de desaceleração no traçado cardiotocográfico foi preditora de acidemia ao nascimento. / A longitudinal prospective study was conducted on 46 pregnancies with umbilical artery abnormal pulsatility index and positive diastolic flow velocity. Patients were evaluated at the Fetal Surveillance Unit/ Obstetrics Clinics of the University of São Paulo Medical School General Hospital (HCFMUSP) between February 2007 and March 2009. The objective of this study was to identify a potential association between fetal antenatal surveillance tests and acidemia at birth, in pregnancies with umbilical artery abnormal Doppler velocimetry and positive diastolic flow. In the same context, this research aimed to establish the correlation of data of birth, and neonatal outcome with umbilical cord pH below 7,20. The development of reversed or absent end- diastolic flow velovity in the umbilical artery was an excluision criteria. The cases were divided in two groups, according to the presence (Group 1) or absence (Group 2) of acidemia at birth (pH below 7.20), based on umbilical cord blood gas measurement immediately after birth. The following variables were submitted to univariate analysis comparing Groups 1 and 2: maternal age, hypertensive syndrome, corticosteroid use (for lung maturation), gestational age at birth, and fetal vitality assessments on the day of delivery. The Doppler parameters analysed were: pulsatility index of the umbilical artery, middle cerebral artery and the pulsatility index for veins for the ductus venosus. The following variables of the fetal biophysical profile were obtained: cardiotocography or nonstress test ( normal/ abnormal), presence of late deceleration, presence of deceleration (late or severe variable decelerations, or prolonged bradycardia), absence of fetal breathing movements, presence of oligohydramnios and biophysical profile score (considered normal when the score was higher than 6). Clinically relevant and statistically significant variables were analyzed by logistic regression. The series included 46 patients divided in Group 1 (n=24 with acidosis) and Group 2 (n=22 without acidosis), and the following variables were statistically correlated to acidemia at birth (p0.05): maternal age, hypertensive syndrome, abnormal cardiotocographic findings, deceleration (late deceleration, or variable deceleration with poor prognosis, or prolonged deceleration), and absence of respiratory movements. On logistic regression, the presence of deceleration was predictive of acidemia (p=0,024; OR=8,2; CI95%=1,2-52). In conclusion, we believe that the presence of acidemia at birth in fetuses with umbilical artery positive diastolic flow and abnormal Doppler velocimetry is mainly associated with abnormality of acute parameters of fetal well-being. The finding of deceleration on cardiotocographic assessments was predictive of acidemia at birth. ____________________

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.

Objetivo: Avaliar a relação entre a classificação do fluxo na onda a do ducto venoso no dia do parto e os resultados pós-natais em gestações com diástole zero ou reversa nas artérias umbilicais. Métodos: Analisou-se retrospectivamente a evolução pós-natal de 103 recém-nascidos de gestações com diagnóstico de diástole zero ou reversa à dopplervelocimetria das artérias umbilicais, no período de janeiro de 1997 a dezembro de 2004. Foram incluídas gestações únicas e fetos sem malformações. Nenhum caso recebeu corticoterapia antenatal. Os casos foram divididos em dois grupos de acordo com a classificação do fluxo na onda a do ducto venoso no dia do parto. Grupo A: 20 casos com fluxo ausente ou reverso e Grupo B: 83 casos com fluxo positivo. Foram avaliados os seguintes resultados pós-natais: idade gestacional no dia do parto, peso de nascimento, Apgar de primeiro e quinto minutos, pH e BE do sangue da artéria umbilical ao nascimento, necessidade de intubação orotraqueal e encaminhamento à unidade de terapia intensiva neonatal, além de: ocorrência de restrição de crescimento fetal, doença das membranas hialinas, pneumotórax, hemorragia pulmonar, displasia broncopulmonar, persistência do canal arterial, sepse, enterocolite necrosante, retinopatia da prematuridade, plaquetopenia, hipoglicemia, hiperglicemia, convulsão, exame neurológico anormal em 24 horas de vida, hemorragia intracraniana, os recém-nascidos foram avaliados durante toda a internação no berçário, sendo registrado o tempo de internação, ocorrência de óbito e causas do óbito. Para análise estatística foram utilizados os testes de Qui-Quadrado, exato de Fisher e Mann-Whitney U, adotado nível de significância de 5%. Resultados: Todos os partos foram cesareanos. A idade gestacional foi semelhante nos dois grupos, 30 semanas no grupo A e 30,9 semanas no B (P=0,23). Observou-se no grupo com fluxo ausente ou reverso da onda a do ducto venoso maior freqüência dos seguintes resultados pós-natais adversos: menor peso ao nascimento (831g vs 1.105g, P<0,001), menores índices de Apgar de primeiro minuto (85% vs 20%, P=0,001) e de quinto minuto (45% vs 10,7%, P =0,001), maior necessidade de intubação orotraqueal (100% vs 48,1%, P=0,001), maior ocorrência de acidose ao nascimento (93% vs 36%, P<0,001), hemorragia pulmonar (40% vs 16,8%, P=0,03), plaquetopenia (65% vs 37,3%, P=0,02), hipoglicemia (85% vs 56,6%, P=0,01), hemorragia intracraniana (52,6% vs 26,3%, P=0,02) e óbito pós natal (65% vs 26,5%, P=0,007). Conclusão: O estudo do fluxo no ducto venoso pode fornecer informações adicionais na programação do momento mais adequado para a interrupção de gestações que cursam com diástole zero ou reversa nas artérias umbilicais em gestações com prematuridade extrema. / Objective: This study was undertaken to analyze the relation between absent or reverse flow during atrial contraction in the ductus venosus on the day of delivery in pregnancies complicated by absent or reversed end-diastolic flow in the umbilical artery and postnatal outcome. Methods: Postnatal outcome of 103 pregnant women with absent or reversed end-diastolic flow (ARED flow) in the umbilical arteries was retrospectively analyzed from January 1997 to December 2004. In this study, only singleton pregnancies that did not take prenatal steroids and with no fetal anomalies were included. The outcome was analyzed in two groups: Group A (n=20), fetuses with absent or reversed ductus venosus flow during the A-wave and group B (n=83) fetuses with a positive flow. After delivery, the following immediate neonatal outcomes of interest were obtained: gestational age at the time of delivery, 1-and 5-minute Apgar scores, umbilical artery pH and base excess, birth weight, need of orotraqueal intubation, and referral to the neonatal intensive care unit. We have also analyzed the incidence of fetal growth restriction, hyaline membrane disease, pneumotorax, lung hemorrhage, bronchopulmonary displasia, persistence of the arterial channel, sepses, necrotizing enterocolitis, retinopathy of prematurity, fetal plaquetopenia, hypoglycemia, hyperglycemia, abnormal neurological exam within 24 hours of life, intracranial hemorrhage, seizures, length of hospitalization, postnatal deaths and its causes. Data were compared by chi-square, Fisher\'s exact test and a Mann-Whitney U test, and the level of significance adopted was of 5%. Results: All newborns were delivered by cesarean section. The average gestational age at birth was 30 weeks in group A and 30,9 in group B (P= 0.23). Fetuses of the group A presented lower birth weight (831g vs 1105g, P< 0.001), lower Apgar score at first (85% vs 20%, P= 0.001), and at fifth minutes (45% vs 10.7%, P =0.001), higher incidence of orotraqueal intubation (100% vs 48.1%, P= 0.001) than fetuses of group B. Group A had also more cases of acidosis (93% vs 36%, P<0.001), lung hemorrhage (40% vs 16,8%, P=0,03), plaquetopenia (65% vs 37.3%, P=0.02), hypoglycemia (85% vs 56.6%, P=0.01), intracranial hemorrhage (52.6% vs 26.3%, P=0.02) and postnatal death (65% vs 26.5%, P=0.007). Conclusion: Ductus venous Doppler can supply additional information regarding the better time to deliver pregnant women with earlier gestational age and with absent or reversed end-diastolic flow (ARED flow) in the umbilical artery.

INTRODUÇÃO: A adiposidade tem sido associada à aterosclerose em vários estudos clínicos. No entanto, poucos estudos de autópsia tem investigado a relação entre adiposidade e aterosclerose sistêmica e os estudos existentes compararam medidas antropométricas e/ou gordura visceral com aterosclerose, porém não avaliaram a aterosclerose em vários sítios em um mesmo indivíduo, avaliando frequentemente apenas a aterosclerose nas artérias coronárias, utilizaram medidas aproximadas de estenose das artérias coronárias, os tamanhos das amostras foram pequenos e os indivíduos eram mais jovens ou de meia-idade. OBJETIVO: Investigar a associação entre adiposidade, mensurada através de medidas antropométricas e a massa de gordura visceral abdominal e torácica com a aterosclerose nas artérias aorta, coronárias, carótidas e cerebrais. MÉTODOS: Trata-se de um estudo transversal em que foram avaliados 240 sujeitos com 30 anos ou mais. Foram coletados dados sociodemográficos, fatores de risco cardiovasculares, medidas antropométricas e massas de gorduras pericárdica e visceral abdominal. O grau de aterosclerose nas artérias aorta, carótidas, coronárias e cerebrais foi avaliado através de medidas morfométricas e o coração foi avaliado quanto à presença de infarto do miocárdio. Foi realizada avaliação da associação entre medidas antropométricas e massa de gordura visceral com a aterosclerose. RESULTADOS: A gordura pericárdica foi associada ao grau de aterosclerose da aorta (p = 0,03). As gorduras viscerais abdominal (p = 0,006) e total (p = 0,006) apresentaram associação com o número de placas nas artérias coronárias. A relação cintura-quadril (RCQ) foi associada ao grau de aterosclerose da artéria aorta (p = 0,005), índice de estenose das artérias coronárias (p = 0,03) e ao número de placas nas artérias coronárias (p = 0,04). CONCLUSÕES: Dentre as medidas antropométricas, a RCQ e as gorduras pericárdica, viscerais abdominal e total foram as mais correlacionadas com o grau de aterosclerose nas diferentes artérias / INTRODUCTION: Adiposity has been associated with atherosclerosis in several clinical studies. However, few autopsy studies have investigated the relationship between adiposity and systemic atherosclerosis and the previous studies compared anthropometric measurements and/or visceral fat with atherosclerosis, but they did not evaluate the atherosclerosis in several sites in the same individual, evaluating only atherosclerosis in coronary arteries, they used approximate stenosis measurements of the coronary arteries, the sample sizes were small and the individuals were younger and middle-aged. AIM: To investigate the association between adiposity, measured by anthropometric measurements and the weight of abdominal visceral and pericardial fat with atherosclerosis in the aorta, coronary, carotid and cerebral arteries. METHODS: This is a cross-sectional study which evaluated 240 subjects aged 30 or more. We collected demographic data, cardiovascular risk factors, anthropometric measurements and weight of pericardial and abdominal visceral fat. The degree of atherosclerosis in the aorta, carotid, coronary and cerebral arteries was evaluated by morphometric measurements and the heart was evaluated for the presence of myocardial infarction. The association between anthropometric measurements and weight of visceral fat with atherosclerosis was evaluated. RESULTS: Pericardial fat was associated with the degree of atherosclerosis of the aorta (p = 0.03). The abdominal (p=0.006) and overall (p=0.006) visceral fat were associated with the number of plaques in the coronary arteries. The waist-to-hip ratio (WHR) was associated with the degree of atherosclerosis of the aorta (p=0.005), stenosis index of the coronary arteries (p=0.03) and the number of plaques in the coronary arteries (p=0.04). CONCLUSIONS: WHR, pericardial, abdominal and total visceral fat were the measurement most correlated with the degree of atherosclerosis in different arteries

No setor de Vitalidade Fetal na Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo foi conduzido estudo caso-controle com seguimento prospectivo com quarenta e seis pacientes. O objetivo desse estudo foi identificar a associação dos testes de avaliação de vitalidade fetal e acidemia ao nascimento em gestações acometidas com dopplervelocimetria anormal e fluxo diastólico positivo das artérias umbilicais. Da mesma maneira, objetivou-se avaliar a relação entre os resultados antenatais, do parto, e neonatais com a ocorrência de pH fetal inferior a 7,20. A evolução para fluxo diastólico ausente ou reverso durante o seguimento foi critério de exclusão. Os casos foram classificados em dois grupos de acordo com a presença (grupo 1), ou ausência (grupo 2) de acidemia ao nascimento (pH inferior a 7,20), por meio da gasometria arterial de cordão imediatamente após o parto. As seguintes variáveis foram submetidas à análise univariada, comparando-se os grupos 1 e 2: idade materna, síndrome hipertensiva, uso de corticóde antenatal para maturação pulmonar, idade gestacional no momento do parto e testes de avaliação de vitalidade fetal do dia do parto. As modalidades dopplervelocimétricas analisadas foram: índice de pulsatilidade do território arterial (representado pela artéria umbilical e artéria cerebral média) e venoso (índice de pulsatilidade para veias do ducto venoso). Os seguintes parâmetros das atividades biofísicas fetais foram estudados: cardiotocografia (normal e anormal), presença de desaceleração tardia, presença de desaceleração (desaceleração tardia, ou desaceleração variável de mau prognóstico, ou desaceleração prolongada), ausência ou não de movimentos respiratórios, presença ou não de oligoâmnio e classificação do escore do perfil biofísico fetal (normal quando maior que 6, e anormal quando menor ou igual a 6). As variáveis clinicamente relevantes e estatisticamente significativas foram analisadas pela regressão logística. A série compôs-se de 46 pacientes classificadas nos grupos 1 (24 casos) e 2 (22 casos) e as seguintes variáveis foram estatisticamente relacionadas à ocorrência de acidemia no nascimento (p0,05): idade materna, síndrome hipertensiva, cardiotocografia anormal, presença de desaceleração, e ausência de movimentos respiratórios. Na regressão logística, a presença de desaceleração foi preditora de acidemia (p=0,024; OR=8,2; IC95%=1,2-52). Os presentes achados sustentam que a presença de acidemia ao nascimento em fetos com dopplevelocimetria anormal e fluxo diastólico positivo das AU está associada principalmente à anormalidade nos parâmetros agudos da avaliação da vitalidade fetal. A presença de desaceleração no traçado cardiotocográfico foi preditora de acidemia ao nascimento. / A longitudinal prospective study was conducted on 46 pregnancies with umbilical artery abnormal pulsatility index and positive diastolic flow velocity. Patients were evaluated at the Fetal Surveillance Unit/ Obstetrics Clinics of the University of São Paulo Medical School General Hospital (HCFMUSP) between February 2007 and March 2009. The objective of this study was to identify a potential association between fetal antenatal surveillance tests and acidemia at birth, in pregnancies with umbilical artery abnormal Doppler velocimetry and positive diastolic flow. In the same context, this research aimed to establish the correlation of data of birth, and neonatal outcome with umbilical cord pH below 7,20. The development of reversed or absent end- diastolic flow velovity in the umbilical artery was an excluision criteria. The cases were divided in two groups, according to the presence (Group 1) or absence (Group 2) of acidemia at birth (pH below 7.20), based on umbilical cord blood gas measurement immediately after birth. The following variables were submitted to univariate analysis comparing Groups 1 and 2: maternal age, hypertensive syndrome, corticosteroid use (for lung maturation), gestational age at birth, and fetal vitality assessments on the day of delivery. The Doppler parameters analysed were: pulsatility index of the umbilical artery, middle cerebral artery and the pulsatility index for veins for the ductus venosus. The following variables of the fetal biophysical profile were obtained: cardiotocography or nonstress test ( normal/ abnormal), presence of late deceleration, presence of deceleration (late or severe variable decelerations, or prolonged bradycardia), absence of fetal breathing movements, presence of oligohydramnios and biophysical profile score (considered normal when the score was higher than 6). Clinically relevant and statistically significant variables were analyzed by logistic regression. The series included 46 patients divided in Group 1 (n=24 with acidosis) and Group 2 (n=22 without acidosis), and the following variables were statistically correlated to acidemia at birth (p0.05): maternal age, hypertensive syndrome, abnormal cardiotocographic findings, deceleration (late deceleration, or variable deceleration with poor prognosis, or prolonged deceleration), and absence of respiratory movements. On logistic regression, the presence of deceleration was predictive of acidemia (p=0,024; OR=8,2; CI95%=1,2-52). In conclusion, we believe that the presence of acidemia at birth in fetuses with umbilical artery positive diastolic flow and abnormal Doppler velocimetry is mainly associated with abnormality of acute parameters of fetal well-being. The finding of deceleration on cardiotocographic assessments was predictive of acidemia at birth. ____________________

Objetivo: Avaliar a relação entre a classificação do fluxo na onda a do ducto venoso no dia do parto e os resultados pós-natais em gestações com diástole zero ou reversa nas artérias umbilicais. Métodos: Analisou-se retrospectivamente a evolução pós-natal de 103 recém-nascidos de gestações com diagnóstico de diástole zero ou reversa à dopplervelocimetria das artérias umbilicais, no período de janeiro de 1997 a dezembro de 2004. Foram incluídas gestações únicas e fetos sem malformações. Nenhum caso recebeu corticoterapia antenatal. Os casos foram divididos em dois grupos de acordo com a classificação do fluxo na onda a do ducto venoso no dia do parto. Grupo A: 20 casos com fluxo ausente ou reverso e Grupo B: 83 casos com fluxo positivo. Foram avaliados os seguintes resultados pós-natais: idade gestacional no dia do parto, peso de nascimento, Apgar de primeiro e quinto minutos, pH e BE do sangue da artéria umbilical ao nascimento, necessidade de intubação orotraqueal e encaminhamento à unidade de terapia intensiva neonatal, além de: ocorrência de restrição de crescimento fetal, doença das membranas hialinas, pneumotórax, hemorragia pulmonar, displasia broncopulmonar, persistência do canal arterial, sepse, enterocolite necrosante, retinopatia da prematuridade, plaquetopenia, hipoglicemia, hiperglicemia, convulsão, exame neurológico anormal em 24 horas de vida, hemorragia intracraniana, os recém-nascidos foram avaliados durante toda a internação no berçário, sendo registrado o tempo de internação, ocorrência de óbito e causas do óbito. Para análise estatística foram utilizados os testes de Qui-Quadrado, exato de Fisher e Mann-Whitney U, adotado nível de significância de 5%. Resultados: Todos os partos foram cesareanos. A idade gestacional foi semelhante nos dois grupos, 30 semanas no grupo A e 30,9 semanas no B (P=0,23). Observou-se no grupo com fluxo ausente ou reverso da onda a do ducto venoso maior freqüência dos seguintes resultados pós-natais adversos: menor peso ao nascimento (831g vs 1.105g, P<0,001), menores índices de Apgar de primeiro minuto (85% vs 20%, P=0,001) e de quinto minuto (45% vs 10,7%, P =0,001), maior necessidade de intubação orotraqueal (100% vs 48,1%, P=0,001), maior ocorrência de acidose ao nascimento (93% vs 36%, P<0,001), hemorragia pulmonar (40% vs 16,8%, P=0,03), plaquetopenia (65% vs 37,3%, P=0,02), hipoglicemia (85% vs 56,6%, P=0,01), hemorragia intracraniana (52,6% vs 26,3%, P=0,02) e óbito pós natal (65% vs 26,5%, P=0,007). Conclusão: O estudo do fluxo no ducto venoso pode fornecer informações adicionais na programação do momento mais adequado para a interrupção de gestações que cursam com diástole zero ou reversa nas artérias umbilicais em gestações com prematuridade extrema. / Objective: This study was undertaken to analyze the relation between absent or reverse flow during atrial contraction in the ductus venosus on the day of delivery in pregnancies complicated by absent or reversed end-diastolic flow in the umbilical artery and postnatal outcome. Methods: Postnatal outcome of 103 pregnant women with absent or reversed end-diastolic flow (ARED flow) in the umbilical arteries was retrospectively analyzed from January 1997 to December 2004. In this study, only singleton pregnancies that did not take prenatal steroids and with no fetal anomalies were included. The outcome was analyzed in two groups: Group A (n=20), fetuses with absent or reversed ductus venosus flow during the A-wave and group B (n=83) fetuses with a positive flow. After delivery, the following immediate neonatal outcomes of interest were obtained: gestational age at the time of delivery, 1-and 5-minute Apgar scores, umbilical artery pH and base excess, birth weight, need of orotraqueal intubation, and referral to the neonatal intensive care unit. We have also analyzed the incidence of fetal growth restriction, hyaline membrane disease, pneumotorax, lung hemorrhage, bronchopulmonary displasia, persistence of the arterial channel, sepses, necrotizing enterocolitis, retinopathy of prematurity, fetal plaquetopenia, hypoglycemia, hyperglycemia, abnormal neurological exam within 24 hours of life, intracranial hemorrhage, seizures, length of hospitalization, postnatal deaths and its causes. Data were compared by chi-square, Fisher\'s exact test and a Mann-Whitney U test, and the level of significance adopted was of 5%. Results: All newborns were delivered by cesarean section. The average gestational age at birth was 30 weeks in group A and 30,9 in group B (P= 0.23). Fetuses of the group A presented lower birth weight (831g vs 1105g, P< 0.001), lower Apgar score at first (85% vs 20%, P= 0.001), and at fifth minutes (45% vs 10.7%, P =0.001), higher incidence of orotraqueal intubation (100% vs 48.1%, P= 0.001) than fetuses of group B. Group A had also more cases of acidosis (93% vs 36%, P<0.001), lung hemorrhage (40% vs 16,8%, P=0,03), plaquetopenia (65% vs 37.3%, P=0.02), hypoglycemia (85% vs 56.6%, P=0.01), intracranial hemorrhage (52.6% vs 26.3%, P=0.02) and postnatal death (65% vs 26.5%, P=0.007). Conclusion: Ductus venous Doppler can supply additional information regarding the better time to deliver pregnant women with earlier gestational age and with absent or reversed end-diastolic flow (ARED flow) in the umbilical artery.

Arterial diseases such as hypertension, carotid stenosis, and abdominal aortic aneurysm (AAA) may progress silently without symptoms and contribute to acute cardiovascular events such as heart attack, stroke, and aneurysm rupture, which are consistently among the leading causes of death worldwide. The arterial pulse wave, regarded as one of the fundamental vital signs of clinical medicine, originates from the heart and propagates throughout the arterial tree as a pressure, flow velocity, and wall displacement wave, giving rise to the natural pulsation of the arteries. The dynamic properties of the pulse wave are intimately related to the physical state of the cardiovascular system. Thus, the assessment of the arterial wall dynamics driven by the pulse wave may provide valuable insights into vascular mechanical properties for the early detection and characterization of arterial pathologies. The focus of this dissertation was to develop and clinically implement Pulse Wave Imaging (PWI), an ultrasound elasticity imaging-based method for the visualization and spatio-temporal mapping of the pulse wave propagation at any accessible arterial location. Motion estimation algorithms based on cross-correlation of the ultrasound radio-frequency (RF) signals were used to track the arterial walls and capture the pulse wave-induced displacements over the cardiac cycle. PWI facilitates the image-guided measurement of clinically relevant pulse wave features such as propagation speed (pulse wave velocity, or PWV), uniformity, and morphology as well as derivation of the pulse pressure waveform. A parametric study investigating the performance of PWI in two canine aortas ex vivo and 10 normal, healthy human arteries in vivo established the optimal image acquisition and signal processing parameters for reliable measurement of the PWV and wave propagation uniformity. Using this framework, three separate clinical feasibility studies were conducted in patients diagnosed with hypertension, AAA, and carotid stenosis. In a pilot study comparing hypertensive and aneurysmal abdominal aortas with normal controls, the AAA group exhibited significantly higher PWV and lower wave propagation uniformity. A “teetering” motion upon pulse wave arrival was detected in the smaller aneurysms (< 5 cm in diameter) but not in the larger aneurysms (> 5.5 cm in diameter). While no significant difference in PWV or propagation uniformity was observed between normal and hypertensive aortas, qualitative differences in the pulse wave morphology along the imaged aortic segment may be an indicator of increased wave reflection caused by elevated blood pressure and/or arterial stiffness. Pulse Wave Ultrasound Manometry (PWUM) was introduced as an extension of the PWI method for the derivation of the pulse pressure (PP) waveform in large central arteries. A feasibility study in 5 normotensive, 9 pre-hypertensive, and 5 hypertensive subjects indicated that a significantly higher PP in the hypertensive group was detected in the abdominal aorta by PWUM but not in the peripheral arteries by alternative devices (i.e. a radial applanation tonometer and the brachial sphygmomanometer cuff). A relatively strong positive correlation between aortic PP and both radial and brachial PP was observed in the hypertensive group but not in the normal and pre-hypertensive groups, confirming the notion that PP variation throughout the arterial tree may not be uniform in relatively compliant arteries. The application of PWI in 10 stenotic carotid arteries identified phenomenon such as wave convergence, elevated PWV, and decreased cumulative displacement around and/or within regions of atherosclerotic plaque. Intra-plaque mapping of the PWV and cumulative strain demonstrated the potential to quantitatively differentiate stable (i.e. calcified) and vulnerable (i.e. lipid) plaque components. The lack of correlation between quantitative measurements (PWV, modulus, displacement, and strain) and expected plaque stiffness illuminates to need to consider several physiological and imaging-related factors such as turbulent flow, wave reflection, imaging location, and the applicability of established theoretical models in vivo. PWI presents a highly translational method for visualization of the arterial pulse wave and the image-guided measurement of several clinically relevant pulse wave features. The aforementioned findings collectively demonstrated the potential of PWI to detect, diagnose, and characterize vascular disease based on qualitative and quantitative information about arterial wall dynamics under pathological conditions.