Orientador: Ana Terezinha Guillaumon / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-28T09:17:18Z (GMT). No. of bitstreams: 1 Siqueira_LeticiaCristinaDalledone_M.pdf: 5041737 bytes, checksum: 615b5b4269f2f46490565662d28dfb21 (MD5) Previous issue date: 2015 / Resumo: Introdução: A espectroscopia próxima ao infra-vermelho (NIRS) é uma técnica não invasiva e de baixo custo que detecta as alterações hemodinâmicas teciduais. O NIRS pode monitorar de forma contínua as informações fisiológicas vasculares intracranianas. Por ser portátil, ele pode ser utilizado a beira do leito e no centro cirúrgico. Objetivo: Avaliar o comportamento das possíveis alterações hemodinâmicas cerebrais, durante a endarterectomia, em pacientes com estenoses maiores que 70%, utilizando NIRS. Casuística e métodos: Foram avaliados 10 voluntários portadores de doença carotídea aterosclerótica com indicação de endarterectomia. Após a seleção dos pacientes que responderam um questionário com dados epidemiológicos e informações referentes a presença de comorbidades, a doença foi confirmada por métodos diagnósticos. No procedimento cirúrgico utilizou-se o NIRS para monitorização. Foram avaliadas as variáveis saturação de oxigênio (Sat O2) hemoglobina total (HbT), hemoglobina reduzida (HbR) e hemoglobina oxigenada (HbO) nos três tempos cirúrgicos pré, trans e pós-clampeamento carotídeo. Resultados: Utilizou-se p<0,05 como nivel de significância. A avaliação dos resultados obtidos através das medidas registradas pelo NIRS permite afirmar que as etapas da cirurgia diferem quanto ás variável HbR e SatO2. Durante a etapa do clampeamento, a variável HbR mostra valores mais elevados que nas outras duas etapas da cirurgia. De outra parte, a variável SatO2 mostra redução durante o clampeamento. Conclusão: O NIRS é um método viável e aplicável de monitorização intracerebral, não-invasivo e em tempo real, durante a endarterectomia carotídea, capaz de medir de forma precisa as mudanças das condições hemodinâmicas capilares intra-cerebrais / Abstract: Introduction: Near-infrared spectroscopy (NIRS) is a low-cost, non-invasive technique that detects tissue hemodynamic alterations. It enables continuous monitoring of the intracerebral vascular physiologic information. Due to its portable nature, NIRS may be used beside a bed or in the operating room. Objective: To evaluate the use of NIRS for intra-surgical monitoring of the brain hemodynamic response, during an endarterectomy procedure of the atherosclerotic carotid artery. Casuistry and Methods: 10 patients with atherosclerotic carotid disease and recommended endarterectomy were evaluated. They were identified in a survey which provided epidemiologic data and the presence of comorbidities. Disease was confirmed by diagnostic methods. NRIS monitoring was used during the surgical procedure. Oxygen saturation (O2 Sat), total hemoglobin (THb), reduced hemoglobin (RHb), and oxyhemoglobin (OHb) were the variables analyzed at the three carotid clamp stages: pre-, trans- and post-. Results: A p<0.05 value was considered statistically significant. The results obtained from the NIRS data reveal that the surgical stages differ in relation to the RHb and O2Sat variables. RHb presents higher levels during clamping when compared with the other two surgical stages. On the other hand, O2Sat is decreased during clamping. Conclusion: NIRS is a feasible, realtime and non-invasive intracranial monitoring method, during carotid endarterectomy, which measures accurately and reliably the changes of the intracerebral capillary hemodynamic conditions / Mestrado / Cirurgia / Mestra em Ciências

Placas ateroscleróticas podem ser estáveis ou vulneráveis à formação de trombo, e os dois processos mais comumente envolvidos a este grave desfecho de trombose luminal são ruptura e erosão de placa. O conhecimento deste estado de vulnerabilidade pode ser importante na prática clínica. A parede arterial é um importante local de modificação proteica em resposta ao estresse. Proteínas em placas ateroscleróticas podem ser nitradas e seu acúmulo durante a aterogênese pode estar relacionado à captação de lipídios. Entre as consequências da nitração proteica, um importante marcador de estresse oxidativo, estão alterações na estrutura, atividade e susceptibilidade a proteólise e estas mudanças podem estar relacionadas a estabilidade da placa. Assim, este estudo teve como objetivo a quantificação e a verificação da distribuição tecidual de proteínas nitradas em segmentos de diferentes graus de vulnerabilidade de um mesmo indivíduo, e a correlação destes marcadores com o perfil histopatológico da placa. Segmentos de diferentes ramos coronários de 30 indivíduos, após infarto agudo do miocárdio fatal, foram estudados. Cinco tipos de placas ateroscleróticas de cada indivíduo foram selecionados, considerando o percentual de estenose e a presença ou não de trombo. Proteínas nitradas totais, linfócitos e macrófagos foram avaliados pela técnica de imuno-histoquímica. Os segmentos apresentando ruptura de placa demonstraram maior número de linfócitos e macrófagos nas camadas adventícia e íntima quando comparados a outros segmentos. A nitração estava relacionada com marcadores histológicos de vulnerabilidade da placa. Além disso, proteínas nitradas estavam diferentemente distribuídas nas camadas do vaso e altos níveis destas proteínas não foram implicados em todos os casos de formação de trombo, já que foi detectado em maior quantidade somente em rupturas de placa e não em casos de erosão de placa. Estes resultados mostram que estresse oxidativo é um importante atributo na diferenciação destes estados patológicos / Atherosclerotic plaques may be stable or vulnerable to thrombus formation. The two processes most commonly involved in this serious outcome of luminal thrombosis are rupture and erosion of the plaque. The knowledge of this vulnerable state of the plaque could be important in clinical practice. The artery wall is an important site of protein modification in response to stress. Proteins in atherosclerotic plaques may be nitrated, and its accumulation during atherogenesis may be related to lipid uptake. The consequences of protein nitration, an important marker of oxidative stress, are changes in its structure, activity and susceptibility to proteolysis and these changes may be related to plaque stability. Thus, this study aimed to quantify and investigate tissue distribution of nitrated proteins in coronary segments of different degrees of vulnerability from the same individual, and correlate these markers with plaque histopathological profile. Segments of coronary branches from 30 patients (after fatal acute myocardial infarct) were studied. Five different types of coronary atherosclerosis plaques from each subject were selected, considering the stenosis percentage and the presence or not of thrombus. Total nitrated protein, lymphocytes and macrophages were assessed by immunohistochemistry. The group presenting disrupted plaque exhibits higher macrophages and lymphocytes content in adventitia an intima layer when compared with other segments. Nitration was related with histological markers of plaque vulnerability. Furthermore, protein nitration was differently distributed in arteries layers and high levels of nitrated proteins were not implicated in all cases of thrombus formation, since it was detected in higher amounts only in ruptured and not in eroded plaques. These findings demonstrates that oxidative stress is an important characteristic in the differentiation of these pathophysiologic states

O treinamento de caminhada (TC) é recomendado para o tratamento de indivíduos com claudicação intermitente (CI) porque melhora a capacidade de caminhada. Além disso, seria interessante que o TC também promovesse modificações benéficas no sistema cardiovascular, pois os eventos cardiovasculares são a principal causa de morte nestes indivíduos. No entanto, os efeitos cardiovasculares do TC em indivíduos com CI foi pouco estudado. Assim, o objetivo deste estudo foi verificar o efeito do TC sobre o risco, a função e a regulação cardiovasculares em indivíduos com CI. Quarenta e dois indivíduos com CI foram divididos de forma aleatória em 2 grupos: controle (GC, n=20, sessões de 30 min de alongamento) e treinamento de caminhada (GT, n=22, 15 séries de 2 min de caminhada em intensidade correspondente à frequência cardíaca (FC) do limiar de dor intercalados por 2 min de repouso passivo). Nos dois grupos, a intervenção foi realizada 2 vezes/semana durante 12 semanas consecutivas. No início e ao final do estudo, os indivíduos realizaram as seguintes avaliações: glicemia e perfil lipídico de jejum; índice de massa corporal; capacidade de caminhada; consumo de oxigênio no 1º estágio e no pico do teste de esforço; índice tornozelo-braço (ITB) de repouso; janela isquêmica após teste ergoespirométrico; pressão arterial (PA) em repouso (auscultatória) e de 24 horas (oscilométrica); débito cardíaco (DC - reinalação de CO2); FC (ECG); volume sistólico (VS); resistência vascular (RV) sistêmica, do antebraço e da perna (plestismografia); componentes de alta (AF) e baixa (BF) frequência da variabilidade da FC; e sensibilidade barorreflexa espontânea (SBR). Mudanças significantes (P<0,05) ao longo do tempo e entre os grupos foram verificadas pela análise de variância ANOVA de dois fatores para medidas repetidas. O TC aumentou significantemente a capacidade de caminhada (&Delta;=+302±85m) e a SBR (&Delta;=+2.13±1.07 ms/mmHg), e diminuiu o VO2) no 1º estágio do teste (&Delta;=-1,8±0,4ml.kg-1.min-1), a janela isquêmica (&Delta;=- 0,40±0,38mmHg.min.m-1), a PA média (&Delta;=-5±2mmHg), a variabilidade da PA média de 24h (&Delta;=-0,8±0,2mmHg), o DC (&Delta;=-0.37±0.24L/min), a FC (&Delta;=- 4±2bpm), a RV do antebraço (&Delta;=-8.5±2.8 U) e a razão BF/AF (&Delta;=-1.24±0.99). A glicemia, o perfil lipídico, o índice de massa corporal, o VO2) pico, o ITB de repouso e a RV sistêmica e da perna não foram modificadas pelo TC. Não houve mudança em nenhuma variável no GC. Em conclusão, o TC melhorou a capacidade de caminhada, a economia de caminhada e a janela isquêmica. Além disso, o TC melhorou a função (PA, DC, FC e RV antebraço) e a regulação (BF/AF e SBR) cardiovasculares em indivíduos com CI. Estas alterações fornecem suporte adicional para a utilização do TC no tratamento de indivíduos com CI / Walking training (WT) is recommended for the treatment of patients with intermittent claudication (IC) because it improves walking capacity. Moreover, it would be interesting that WT also promotes beneficial changes on cardiovascular system, since cardiovascular events are the main causes of death in these patients. Nevertheless, the effects of WT on cardiovascular system in patients with IC have been poorly studied. Thus, the objective of this study was to investigate the effects of WT on cardiovascular risk, function and regulation in patients with IC. Forty-two IC patients were randomly divided into 2 groups: Control (CG, n=20, 30 min of stretching exercises) and walking training (TG, n=22, 15 sets of 2:2-min walk:rest at the heart rate (HR) of pain threshold). In both groups, the intervention was performed twice/week for 12 consecutive weeks. At the beginning and end of the study, the following measured were done: fasting glycemia and lipid profile; body mass index; walking capacity; VO2 at the first stage and the peak of a treadmill test; ankle brachial index (ABI); ischemic window after maximal test; resting (auscultatory) and 24-hour (oscillometric) blood pressure (BP); cardiac output (CO - CO2 rebreathing); heart rate (HR - ECG); stroke volume (SV); systemic, forearm and leg vascular resistance (VR - plethysmography); low- (LF) and high-frequency (HF) components of HR variability; and spontaneous baroreflex sensitivity (SBS). Significant changes (P<0.05) over time and between groups were assessed by 2-way ANOVA for repeated measures. WT significantly increased walking capacity (&Delta;=+302±85m) and SBS (&Delta;=+2.13±1.07 ms/mmHg), and decreased VO2 at the first stage of treadmill test (&Delta;=-1.8±0.4ml.kg-1.min-1), ischemic window (&Delta;=-0.40±0.38mmHg.min.m-1), mean BP (&Delta;=-5±2mmHg), ambulatory mean BP variability (&Delta;=-0,8±0,2 mmHg), CO (&Delta;=-0.37±0.24 L/min), HR (&Delta;=- 4±2bpm), forearm VR (&Delta;=-8.5±2.8 U) and LF/HF (&Delta;=-1.24±0.99). Glycemia, lipid profile, body mass index, VO2 peak, ABI, systemic and leg VR were unchanged following WT. There was no significant change for any variable in CG. In conclusion, WT enhanced walking capacity, walking economy and ischemic window. In addition, WT improved cardiovascular function (BP, CO, HR and forearm VR) and autonomic regulation (LF/HF, SBS) in patients with IC. These changes provide further support for the use of regular WT in treating patients with IC

INTRODUÇÃO: Historicamente, os procedimentos de revascularização do miocárdio (cirúrgicos ou percutâneos) foram admitidos como opções terapêuticas efetivas para a proteção, em curto e médio prazo, do miocárdio isquêmico em pacientes portadores de doença arterial coronária. Todavia, não está estabelecido se tais procedimentos são essenciais para a preservação da função ventricular, nem se a ausência dos mesmos contribui para sua piora. OBJETIVOS: Avaliar a evolução da fração de ejeção (FEVE) em pacientes portadores de doença multiarterial coronariana crônica estável, e com função ventricular esquerda preservada, dez anos após terem sido submetidos a três diferentes estratégias terapêuticas: revascularização cirúrgica do miocárdio (RM), angioplastia coronária percutânea (ATC) ou tratamento medicamentoso (TM) isoladamente (subestudo do MASS II). MÉTODOS: Realizou-se o ecocardiograma transtorácico com doppler para avaliação da FEVE em pacientes portadores de DAC multiaterial estável no início do estudo e após dez anos das intervenções. O cálculo da FEVE foi realizado pelos métodos de Teichholz ou bidimensional. RESULTADOS: Dos 611 pacientes integrantes do estudo MASS II, 422 pacientes estavam vivos ao término de 10,32 (±1,43) anos de seguimento; destes, 108 pacientes do grupo TM, 111 do RM e 131 do ATC realizaram reavaliação ecocardiográfica da função ventricular. As principais características demográficas, clínicas e angiográficas foram semelhantes nos 3 grupos, bem como a ocorrência de infarto agudo do miocárdico (IAM). A FEVE foi semelhante entre os grupos no início do estudo (0,61 + 0,07, 0,61 + 0,08 e 0,61 + 0,09, respectivamente, para os grupos ATC, RM e TM [p=0,675]) e ao término do seguimento (0,56 + 0,11, 0,55 + 0,11 e 0,55 + 0,12, respectivamente, para os grupos ATC, RM e TM [p=0,675]). Observou-se redução da função ventricular (p<0,001) nos três grupos terapêuticos de forma semelhante (p=0,641). Outras variáveis, como gênero, diabetes, idade, padrão arterial, necessidade de ATC ou RM adicionais, não influenciaram a evolução da FEVE. Porém, a ocorrência de IAM foi responsável por acentuada queda da FEVE (delta de decréscimo de 18,29 + 21,22% e 6,63 + 18,91% para pacientes com e sem IAM, respectivamente [p=0,001]). Além disso, a presença de IAM prévio à randomização e IAM durante o seguimento foram associadas a desenvolvimento de disfunção ventricular, definida como FEVE < 45%. CONCLUSÃO: Pacientes do grupo clínico portadores de DAC multiarterial desprotegida pelas estratégias de revascularização não apresentaram prejuízo adicional na função ventricular em comparação ao observado nos grupos cirúrgico e angioplastia. Além disso, qualquer que tenha sido a estratégia terapêutica aplicada, a função ventricular permaneceu preservada na ausência de infarto agudo do miocárdio / BACKGROUND: Historically, myocardial revascularization procedures, either by coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI), are assumed as effective therapeutic options for the protection of the ischemic myocardium. However, it is not established if those procedures are responsible for left ventricular function preservation, or even if their absence may contribute for the deterioration of left ventricular ejection fraction (LVEF). OBJECTIVES: to evaluate the evolution of LVEF in patients with chronic multivessel coronary heart disease and left ventricular function initially preserved, submitted to CABG, PCI or medical treatment (MT), after ten years of follow-up (MASS II substudy). METHODS: Transthoracic echocardiography was performed in patients with multivessel coronary heart disease, participants of MASS II trial, previously to randomization for one of the three possible therapeutic strategies (CABG, PCI and MT), and after 10 years of follow-up. LVEF was measured by the biplane method (Simpson) or alternatively by the Teichholz method. RESULTS: Of the 611 patients participants of MASS II trial, 422 were alive after a follow-up of 10.32 (±1.43) years. 350 had LVEF reassessed: 108 patients in MT group, 111 in CABG group and 131 in PCI group. Main baseline characteristics were similar among the three groups, including demographic, angiographic and laboratorial findings. The occurrence of acute myocardial infarction (AMI) was also similar among the 3 groups. There was no difference of LVEF either at the beginning (0.61 + 0.07, 0.61 + 0.08 e 0.61 + 0.09 respectively for PCI, CABG and MT, p=0.675) and the end of follow up (0.56 + 0.11, 0.55 + 0.11 e 0.55 + 0.12 respectively for PCI, CABG and MT groups, p=0.675). However, there was a slight, but significant reduction (P<0.001) of LVEF, similar on the three therapeutic groups (p=0.641). The impact of other variables over LVEF evolution, such as gender, age, diabetes, arterial pattern (including, left anterior descending coronary artery commitment) and additional revascularization, were also analyzed, with no influence on the evolution of LVEF. However, the presence of previous AMI (OR 2.50, 95% CI 1.40-4.45; p= 0.0007) and the occurrence of AMI during follow up (OR 2.73, 95% IC 1.25- 5.92; p=0.005) were associated with an increased risk of developing LVEF < 45%. Also, AMI during follow-up was responsible for a greater reduction of LVEF (reduction delta of 18.29 ± 21.22% and 6.63 ± 18.91%, respectively for patients with and without AMI during follow-up, p=0.001). CONCLUSION: Compared with PCI or CABG, the Medical group, with unprotected coronary disease by mechanical revascularization, showed no differences in left ventricular function after 10 years of follow-up. Moreover, regardless of therapeutic strategy applied, ventricular function remained preserved without AMI

Introdução:O diabetes mellitus tipo 2 (DM2) está associado ao aumento da mortalidade por doença arterial coronária (DAC). O DM2 afeta o metabolismo de lípides, levando à dislipidemia, caracterizada por hipertrigliceridemia e baixa concentração plasmática de HDL-colesterol. Transferências de lípides entre HDL e outras lipoproteínas são passos cruciais no metabolismo e função da HDL. Objetivo: Investigar se o desenvolvimento de DAC em pacientes com DM2 está associado com alterações na transferência de lípides para HDL. Métodos: Foram estudados 79 pacientes com DM2 portadores de DAC obstrutiva (DM2-DAC) e 76 pacientes com DM2 e artérias coronárias angiograficamente normais (DM2). Foram avaliados o perfil lipídico, apolipoproteínas, composição lipídica da HDL, dosagem de CETP e LCAT. No ensaio de transferência, as amostras de plasma foram incubadas por 1h a 37º com uma nanoemulsão artificial marcada com 3H-éster de colesterol e 14Cfosfolípides ou 3H -triglicérides e 14C-colesterol não esterificado. A quantificação da transferência de lípides da nanoemulsão doadora para a HDL foi feita após a precipitação da fração não HDL. O tamanho da HDL foi medido por laser light scattering. Resultados: Os pacientes DM2-DAC apresentaram maior concentração de colesterol total (DM2-DAC=218±48; DM2=193±36; p < 0,001), LDL-C (147±44 vs 124±33; p < 0,001) e apoB (103,1±20,4 vs 96,0 ± 19,5; p = 0,03) que o grupo sem DAC. Os grupos não mostraram diferença com relação à concentração plasmática de triglicérides (DM2-DAC=171 ± 73; DM2=154 ± 70; p=0,1) e HDL-C (41±9 vs 38±8; p=0,07). A transferência de éster de colesterol (4,0 ± 0,6 vs 4,3 ± 0,7; p=0,005) e de colesterol não esterificado (7,6 ± 1,2 vs 8,2±1,5; p=0,006) foi menor no grupo com DAC, porém esse grupo teve maior concentração de colesterol não esterificado no plasma (36,3 ± 8,0 vs 33,6±6,5 ;p=0,02). A concentração de CETP foi menor no grupo DM2DAC (2,1±1,0 vs 2,5 ±1,1; p=0,02 ). O diâmetro das partículas de HDL não diferiu entre os grupos (8,9 ± 1,2 vs 9,0±0,6; p=0,4), nem a composição lipídica da HDL (éster de colesterol: 52,2 ± 10,8 vs 50,6 ± 10,7; p=0,38; colesterol não esterificado: 9,0 ± 2,8 vs 8,4 ± 2,7; p=0,19; triglicérides: 13,4 ± 3,9 vs 12,4 ± 3,9; p=0,11e fosfolípides:77,2 ± 16,7 vs 78,8 ± 20,5; p=0,60). A atividade da enzima LCAT não diferiu entre os grupos (1,34 ± 0,12 vs 1,33 ± 0,10; p=0,9). As transferências de todos os lípides apresentaram correlação entre si. Na análise multivariada, a presença de DAC influenciou a transferência de éster de colesterol, quando ajustado para HDL-C, apoA1, CETP massa e LDL-C (r2=0,5, p=0,03) e a transferência de colesterol não esterificado, quando ajustado para apoA1, apoB, LCAT, glicemia, idade e sexo (r2 = 0,7, p = 0,003). Conclusão: Na amostra estudada, pacientes diabéticos portadores de DAC apresentam menor transferência de colesterol para HDL comparados com os pacientes diabéticos sem DAC obstrutiva / Aim: Type 2 diabetes mellitus (DM2) is associated with morbidity and mortality secondary to coronary artery disease (CAD). DM2 affects lipid metabolism, and diabetic dyslipidemia is characterized by increased levels of tryglicerides and reduced levels of HDL-cholesterol. Lipid transfer between HDL and the other lipoproteins is a crucial step in HDL function and metabolism. Objective: The purpose of this study was investigate whether the susceptibility of patients with type 2 diabetes mellitus to develop CAD is related with alterations in lipid transfers to HDL. Methods: 79 patients with DM2 and obstructive CAD (DM2- CAD) and 76 with DM2 (DM2 group) and angiographic normal coronary arteries were studied. Lipid profile, apolipoproteins, HDL lipid composition, CETP and LCAT activity were evaluated. In the lipid transfer assay, fasting plasma samples were incubated for 1h at 37°C with a donor artificial nanoemulsion labeled with 3H -cholesteryl-esters and 14C-phospholipids or 3H-triglycerides and 14C-unesterified cholesterol. Radioactive lipids transferred from the donor nanoemulsion to HDL were quantified in the supernatant after chemical precipitation of non-HDL fractions and nanoemulsion. HDL size was measured by laser light scattering. Results: In DM2-CAD, total cholesterol (DM2- DAC=218 ± 48; DM2=193±36; p < 0,001), LDL-C (147 ± 44 vs 124±33; p < 0,001) and apoB (103,1±20,4 vs 96,0±19,5; p=0,03) were higher than in DM2 group. The groups showed no differences with respect to plasma triglycerides levels (DM2-DAC=171± 73; DM2=154 ± 70; p=0,1) nor HDL-C (41 ± 9 vs 38±8; p=0,07). DM2-CAD showed diminished transfer to HDL of esterified cholesterol (4,0±0,6 vs 4,3 ± 0,7; p = 0,005) and unesterified cholesterol (7,6 ± 1,2 vs 8,2 ± 1,5; p=0,006). However, the DM2-CAD group showed higher levels of plasmatic unesterified cholesterol (36,3±8,0 vs 33,6±6,5 ;p=0,02). CETP mass was lower in the DM2- CAD group (2,1 ± 1,0 vs 2,5 ± 1,1; p=0,02 ). HDL particle diameter was not different between groups (8,9±1,2 vs 9,0 ± 0,6; p=0,4) neither its lipid composition (esterified cholesterol: 52,2 ± 10,8 vs 50,6 ± 10,7; p=0,38; unesterified cholesterol: 9,0 ± 2,8 vs 8,4 ± 2,7; p=0,19; triglycerides: 13,4 ± 3,9 vs 12,4 ± 3,9; p=0,11; phospholipids: 77,2 ± 16,7 vs 78,8 ± 20,5; p=0,60). LCAT activity was not different in the two groups (1,34±0,12 vs 1,33±0,10; p=0,9). In multivariate analysis, DAC influenced cholesteryl ester transfer, when adjusted to HDL-C, apoA1, CETP mass and LDL-C (r2=0,5, p=0,03), and unesterified cholesterol transfer, when adjusted to apoA1, apoB, LCAT, glycemia, age and sex (r2=0,7, p=0,003). Conclusion: In these sample, DM2-CAD patients show diminished cholesterol transfer to HDL particles when compared to diabetic patients without obstructive CAD

No description available.

Les nucléotides cycliques (NC) apparaissent comme des régulateurs majeurs du tonus vasculaire. Produits dans les cellules musculaires lisses (CMLs) par les cyclases, les NC agissent par l’intermédiaire des protéines effectrices qui modulent de nombreux mécanismes régulateurs de la vasomotricité. Les phoshodiestérases (PDEs) qui dégradent les NC assurent le contrôle spatiotemporel de leur réponse biologique. L’objectif de mon travail était de préciser les mécanismes par lesquels le tonus artériel est contrôlé par certaines PDEs. J’ai réalisé cette exploration en utilisant des artères coronaires ou mésentériques de rat, en situation physiologique puis dans un modèle d’insuffisance cardiaque (IC) chronique.Dans la première partie de mon travail, nous nous sommes intéressés au mécanisme par lequel les PDE3 et PDE4 régulent le tonus de l’artère coronaire.Par une approche expérimentale plus intégrée de réactivité vasculaire sur artère coronaires isolées, nous avons montré l’importance du canal potassique BK(Ca) dans l’effet relaxant des inhibiteurs de PDE3 et PDE4. De plus, nous avons constaté une contribution différentielle de ces canaux selon le mode de stimulation de la génération d’un NC, l’AMPc. A l’échelle de la CML, notre étude a permis de suggérer l’existence d’un signalosome impliquant les PDE3/PDE4 et du canal potassique BK(Ca), indiqué par la technique de Proximity Ligation Assay. En accord avec cette hypothèse, le contrôle des BK(Ca) par ces PDEs a pu être mis en évidence par la technique du Patch-Clamp. De manière intéressante, la contribution du couplage fonctionnel entre le canal BKCa et les PDE3 et PDE4 n’a pas été retrouvée dans les artères isolées de rats atteints d’IC. Ceci pourrait être expliqué par une diminution de l’expression des canaux BK(Ca) ainsi que, au moins partiellement, par une raréfaction de leur localisation à proximité de la PDE4B.Dans la deuxième partie de mon travail nous avons exploré les rôles des PDE3, PDE4 et de la PDE2 en particulier, dans la régulation du tonus de l’artère mésentérique de rats atteints d’IC, en comparaison aux rats contrôles. En effet, la contribution de la PDE2 est suggérée par la capacité d’un inhibiteur sélectif de cette enzyme à diminuer la réponse des artères isolées à une stimulation vasocontractante. Nous avons ensuite exploré les effets de cet inhibiteur dans d’autres types de réponses impliquant les NC.L’ensemble de ces travaux ajoute un niveau de complexité à la compréhension des mécanismes de la régulation de la vasomotricité des artères de résistance par les PDEs. Les altérations de cette voie de signalisation que nous avons mises en évidence dans l’IC pourraient contribuer à la dysfonction vasculaire qui accompagne la maladie. / Cyclic nucleotides (CN) appears to be important regulator of vascular tone. Produced in smooth muscle cells (SMCs) by cyclases, CN act through activation of key effectors involved in the regulation of vascular tone. Phoshodiesterases (PDEs), which degrade CN, provide spatiotemporal control of their biological responses. The aim of my work was to understand how vascular tone is controlled by some PDEs and how it is altered during heart failure (HF). For this, I used rat coronary and mesenteric arteries.In the first part of my work, we were interested in defining the contribution of PDE3 and PDE4 in the regulation of coronary tone. Using vascular reactivity technique, we demonstrate the importance of large-conductance Ca2+-activated potassium channel (BK(Ca)) channel in the relaxant effect of PDE3 and PDE4 inhibitor. Moreover, their contribution was different depending on the mode of cAMP production, a type of CN. At the cellular level, Proximity Ligation Assay experiments suggest the existence of a signalosome that involves PDE3/PDE4 andBK(Ca). According to this result, the control of BK(Ca) activity by these PDEs was demonstrated using the Patch-Clamp technique. Interestingly, the contribution of the functional coupling involving the BK(Ca) and PDE3/PDE4 is lost during HF. This may be explained by the decrease of BK(Ca) expression and [BK(Ca)-PDE4B] duplex signal in coronary arteries isolated from HF rat.In the second part of my work, we investigated the role of PDE3, PDE4 and PDE2 particularly, in the regulation of rat mesenteric artery tone during HF. In fact, PDE2 selective inhibitor, decreased the contractile response of isolated arteries. Then, we investigated the effect of PDE2 inhibition in other pathway that involve CN.Our findings underline the complexity of PDEs in the regulation of resistance artery tone. During HF, some CN signaling pathway are impaired leading to vascular dysfunction which can aggravate the pathology.

With old age, blood flow to the high-oxidative red skeletal muscle is reduced and blood flow to the low-oxidative white muscle is elevated during exercise. Changes in the number of feed arteries perforating the muscle are thought to contribute to this altered hyperemic response during exercise. We tested the hypothesis that exercise training would ameliorate age-related differences in blood flow during exercise and feed artery structure in skeletal muscle. Young (6–7 mo old, n = 36) and old (24 mo old, n = 25) male Fischer 344 rats were divided into young sedentary (Sed), old Sed, young exercise-trained (ET), and old ET groups, where training consisted of 10–12 wk of treadmill exercise. In Sed and ET rats, blood flow to the red and white portions of the gastrocnemius muscle (GastRed and GastWhite) and the number and luminal cross-sectional area (CSA) of all feed arteries perforating the muscle were measured at rest and during exercise. In the old ET group, blood flow was greater to GastRed (264 ± 13 and 195 ± 9 ml·min−1·100 g−1 in old ET and old Sed, respectively) and lower to GastWhite (78 ± 5 and 120 ± 6 ml·min−1·100 g−1 in old ET and old Sed, respectively) than in the old Sed group. There was no difference in the number of feed arteries between the old ET and old Sed group, although the CSA of feed arteries from old ET rats was larger. In young ET rats, there was an increase in the number of feed arteries perforating the muscle. Exercise training mitigated old age-associated differences in blood flow during exercise within gastrocnemius muscle. However, training-induced adaptations in resistance artery morphology differed between young (increase in feed artery number) and old (increase in artery CSA) animals. The altered blood flow pattern induced by exercise training with old age would improve the local matching of O2 delivery to consumption within the skeletal muscle.

This master's thesis deals with pulsating flow of Newtonian and non-Newtonian fluid. Theoretical part represents necessary theoretical knowledge for pulsating flow and understanding of non-Newtonian behaviour. Furthermore the thesis focus is directed on numerical simulation of pulsating flow in straight, ideally rigid tube and in patient-specific model of human artery, more precisely in carotid. Two methods are used: numerical solution based on finite volume method (FVM) and also analytical solution using Bessel functions by Womersley. Results are validated against experimental measurements of velocity profiles by particle image velocity method (PIV). The agreement between numerical and experimental data with consideration of PIV inaccuracy was was very good from both point of views - qualitative and quantitative. Numerical solution also compare influence of turbulence and non-Newtonian behaviour towards base (laminar flow, Newtonian fluid). Developed methodology is then applied on patient-specific model of carotid, which was renovated from computed tomography. Measurements in vivo in human arteries is very expensive and often invasive. Because of that measurement outputs are limited, most of the time on pressure and flow. Computational fluid dynamics (CFD) is non-invasive and outputs are through whole domain. Due to these advantages CFD significantly contributes to understanding of hemodynamics influence in cardiovascular diseases.

Hjärt- och kärlsjukdomar är den största dödsorsaken i världen. En av behandlingarna som kan ges vid detta är koronar bypass operation. Väntan inför denna operation kan upplevas oviss och skapa oro hos patienten. Syftet med litteraturstudien var att undersöka patientens upplevelse i väntan på koronar bypass operation. Metod: Studien genomfördes som en allmän strukturerad litteraturstudie med induktiv ansats där sex kvalitativa, en kvantitativ samt en artikel med mixad metod erhölls. Data bearbetades genom en innehållsanalys. Resultat: Resultatet visade att patienter upplever såväl emotionell som somatisk påfrestning i väntan på koronar bypass operation. De mest framträdande upplevelserna var att patienterna upplevde ängslan och oro, ovisshet, rädsla och fysiska restriktioner. Dessa upplevelser mynnade ut till två teman den emotionella väntan och den somatiska väntan. Konklusion: I väntan på koronar bypass operation var de mest framträdande upplevelserna ovisshet samt ängslan och oro. För att reducera ovissheten, ängslan och oron var det av största vikt att sjuksköterskan arbetade personcentrerat. En sjuksköterskeledd intervention samt möjlighet att prata med tidigare koronar bypass operation patienter visade en signifikant reducering av den emotionella påfrestningen. En ökad förståelse för patienters upplevelse i väntan på koronar bypass operation är av stor vikt för att möjliggöra personcentrerad omvårdnad. / Cardiovascular disease is the leading cause of death in the world. One of the treatments for this is to undergo a coronary artery bypass graft. The waiting time before surgery causes uncertainty and worry in some patients. The aim was to examine patients’ experience while waiting for coronary artery bypass. The Method used was a general structured literature study with an inductive approach, where sixarticles with a qualitative approach, one quantitative and one with mixed method were found. The data was processed through a content analysis. The Result showed that patients experience both emotional and somatic stress while waiting for coronary artery bypass surgery. The most dominant experiences and emotions that patients felt were anxiety, uncertainty, fear, and physical restrictions. These experiences and emotions resulted in two themes Emotional waiting and Somatic waiting. TheConclusion showed to reduce uncertainty and anxiety it was of the utmost importance that the nurse applied person-centered care. A nurse-led intervention as well as the opportunity to talk with former coronary artery bypass patients showed a significant reduction in emotional strain. An increased understanding of patient´s experience while waiting for coronary artery bypass is of great importance to enable person-centered care.