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Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

No presente estudo, duas importantes situações foram abordadas no intuito de se melhor entender os mecanismos homeostáticos dos pressorreceptores na gênese da hipertrofia cardíaca em resposta à hipertensão renovascular: o efeito do tempo de clipe na artéria renal e o efeito dos níveis pressóricos e da variabilidade da pressão arterial. O curso temporal mostrou que, antes mesmo da instalação da hipertensão, há alteração da morfologia cardíaca, qual seja o desenvolvimento de uma hipertrofia ventricular excêntrica e, como forma de mecanismo compensatório, um aumento da expressão de algumas proteínas da homeostase do cálcio (fosfolambam fosforilada pela serina-16 e corrigido pelo fosfolambam total em 100% e fosfolambam fosforilado pela treonina-17 e corrigido pelo fosfolambam total em 54%). Uma vez instalada a hipertensão, observou-se um remodelamento ventricular esquerdo para o tipo concêntrico, com prejuízo da função diastólica e um desbalanço do sistema nervoso autonômico, com aumento da atividade simpática, observado pelo aumento da razão dos componentes de baixa freqüência (LF) e alta freqüência (HF) no tacograma (0,44 ± 0,10 vs. 0,20 ± 0,03 nos controles). A análise do efeito da pressão arterial e da variabilidade da pressão arterial mostrou uma correlação positiva com o grau de hipertrofia ventricular esquerda (r=0,76, p<0,01). A secção cirúrgica dos pressorreceptores somada à implantação do clipe na artéria renal mostrou adaptações cardiovasculares em níveis semelhantes (mesmo nível de hipertensão) e, por vezes maiores (modulação simpática para o coração e para os vasos, hipertrofia ventricular esquerda e disfunção diastólica), ao grupo cuja artéria renal foi estenosada e que permaneceu com os barorreceptores intactos. Estas respostas aconteceram num período de tempo três vezes menor na ausência do barorreflexo. Tais observações ressaltam o importante efeito homeostático do barorreflexo na gênese das respostas cardíacas adaptativas à hipertensão arterial / In the present study, two important situations were observed to evaluate the role of the baroreceptors in the genesis of cardiac hypertrophy in response to hypertension: the effect of the time-course of the clip in the renal artery and the effect of the level of arterial blood pressure (ABP) and blood pressure variability (ABPV). The time-course evaluation showed that even before hypertension was installed, cardiac alterations could be observed, as a left ventricular eccentric hypertrophy. Compensatory mechanisms, such as an increase in some calcium homeosthatic proteins, could also be noticed (increase in phosphorilated phospholmaban at threonin-17 corrected by total phospholamban in 54% and increase in phosphorilated phospholmaban at serine-16 corrected by total phospholamban in 100%). However, once hypertension was established, left ventricle morphology changed to a concentric hypertrophy, accompanied by a diastolic dysfunction and enhanced sympathetic modulation, observed by relation between low-frequency component (LF) and high-frequency component (HF) at tachogram (0,44 ± 0,10 vs. 0,20 ± 0,03 in control group). ABP and ABPV analyses showed an important positive correlation with the degree of left ventricular hypertrophy (r=0,76, p<0,01). However, the absence of baroreceptors in one of the hypertensive groups, evoked the same cardiovascular alterations (same level of hypertension) or even worse (sympathetic modulation for heart and vessels, left ventricular hypertrophy and diastolic dysfunction) reached by the hypertensive baroreceptors-preserved group. These cardiovascular responses were observed in a period that correspond one third of time to the group with intact baroreflex. These observations lead us to conclude the importance of homeosthatic effects of the baroreflex in the genesis of cardiac responses to hypertension

O remodelamento cardíaco é uma sequela da hipertensão. Receptores do tipo Toll (TLRs) pertencem a imunidade inata e sua ativação produz moléculas inflamatórias. O objetivo do trabalho foi avaliar a participação do TLR4 no remodelamento cardíaco de ratos espontaneamente hipertensos (SHR). Utilizamos SHR e Wistar de 6 e 21 semanas. O nível do RNAm do TLR4 de SHR de 21 semanas é maior em relação aos outros grupos. Outros grupos de Wistar e SHR de 19 semanas foram tratados com anticorpo anti-TLR4, os controles receberam anticorpo IgG inespecífico. Observamos redução no nível do RNAm do TLR4 e MyD88 e expressão protéica do TLR4, MyD88, TNF-<font face=\"symbol\">a e IL-1<font face=\"symbol\">b de SHR anti-TLR4 em relação aos SHR controle. Não houve alteração nos valores pressóricos. Verificamos redução no nível do RNAm de colágenos I e III, de metaloproteinases 2 e 9, de ANP, BNP e <font face=\"symbol\">a-actina esquelética e de deposição de colágeno, área e diâmetro de cardiomiócitos de SHR anti-TLR4 em relação aos SHR controle. Nossos resultados sugerem que o TLR4 participa do processo de remodelamento cardíaco de SHR adultos. / The cardiac remodeling is a sequel of hypertension. Toll-Like Receptors (TLR) are innate immunity receptor and its activation produces inflammatory molecules. The objective of this study was to evaluate the involvement of TLR4 in cardiac remodeling of spontaneously hypertensive rats (SHR). We used male Wistar and SHR with 6 and 21 weeks. The level of TLR4 mRNA in SHR with 21 weeks is higher than the other groups. Wistar and SHR with 19 weeks were treated with anti-TLR4 or nonspecific IgG antibody (control group). We observed a reduction in the level of TLR4 and MyD88 mRNA and protein expression of TLR4, MyD88, TNF-<font face=\"symbol\">a and IL-1<font face=\"symbol\">b in anti-TLR4 SHR compared to control SHR. There was no change in blood pressure values in SHR after anti-TLR4 treatment. We observed reduction in mRNA level of collagens I and III, metalloproteinases 2 and 9, ANP, BNP, <font face=\"symbol\">a-skeletal actin, collagen deposition, cardiomyocyte area and diameter in anti-TLR4 SHR compared to control SHR. Our results suggest that TLR4 participates of cardiac remodeling process in adults SHR.

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<p>Left ventricular hypertrophy (LVH) and the insulin resistance syndrome are common conditions associated with a markedly increased cardiovascular risk. In a fairly large prospective longitudinal study of men from the general population, we found that an unfavorable serum fatty acid profile and components of the insulin resistance syndrome such as dyslipidemia, obesity and hypertension at age 50 predicted the prevalence of LVH at age 70. In cross-sectional analyses at age 70, several components of the insulin resistancesyndrome were significantly related to left ventricular relative wall thickness and concentric remodeling, but less to LVH. Left ventricular relative wall thickness was inversely related to insulin sensitivity in skeletal muscle and borderline significantly directly related to insulin sensitivity in the myocardium in a healthy, normotensive sample of the cohort investigated with positron emission tomography, whereas left ventricular mass index was not related to myocardial or skeletal muscle insulin sensitivity. At age 70, echocardiographic LVH was related to a variety of common electrocardiographic diagnoses. In a prospective mortality analysis with baseline at age 70 and a median follow-up time of five years, echocardiographic and electrocardiographic LVH predicted mortality independently of each other and of other cardiovascular risk factors, implying that echocardiographic and electrocardiographic LVH in part carry different prognostic information.</p><p>In summary, components of the insulin resistance syndrome predicted LVH twenty years later, but were cross-sectionally more related to increased left ventricular relative wall thickness and concentric remodeling. Echocardiographic and electrocardiographic LVH predicted mortality independently of each other and of components of the insulin resistance syndrome.</p>

Left ventricular hypertrophy (LVH) and the insulin resistance syndrome are common conditions associated with a markedly increased cardiovascular risk. In a fairly large prospective longitudinal study of men from the general population, we found that an unfavorable serum fatty acid profile and components of the insulin resistance syndrome such as dyslipidemia, obesity and hypertension at age 50 predicted the prevalence of LVH at age 70. In cross-sectional analyses at age 70, several components of the insulin resistance syndrome were significantly related to left ventricular relative wall thickness and concentric remodeling, but less to LVH. Left ventricular relative wall thickness was inversely related to insulin sensitivity in skeletal muscle and borderline significantly directly related to insulin sensitivity in the myocardium in a healthy, normotensive sample of the cohort investigated with positron emission tomography, whereas left ventricular mass index was not related to myocardial or skeletal muscle insulin sensitivity. At age 70, echocardiographic LVH was related to a variety of common electrocardiographic diagnoses. In a prospective mortality analysis with baseline at age 70 and a median follow-up time of five years, echocardiographic and electrocardiographic LVH predicted mortality independently of each other and of other cardiovascular risk factors, implying that echocardiographic and electrocardiographic LVH in part carry different prognostic information. In summary, components of the insulin resistance syndrome predicted LVH twenty years later, but were cross-sectionally more related to increased left ventricular relative wall thickness and concentric remodeling. Echocardiographic and electrocardiographic LVH predicted mortality independently of each other and of components of the insulin resistance syndrome.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Sub-endocardial fibres line the inner surface of both ventricles and are responsible for longitudinal oscillations of the mitral annulus, such oscillations may be measured using tissue Doppler echocardiography (IDE). During systole the annulus descends and during early diastole (ETDE) and atrial systole (ATDE) itascends. This thesis examined whether changes in the velocity of the annulus ineach of these phases of oscillation, measured using tissue Dopplerechocardiography (TDE), could determine the nature of increases in left ventricular size (pathological or physiological). Study one examined differences at rest in longitudinal velocities between individuals with hypertrophic cardiomyopathy (HCM), hypertension (HT), weightlifters, runners and controls, (n = 15 all groups) and all groups were aged between 20 - 36 years. The results demonstrated that both pathological groups had systolic and ETDE velocities significantly lower than groups with physiological hypertrophy (weightlifters or runners) or controls p < 0.05. AIDE however was not significantly different between groups. Additionally runners also demonstrated a significantly higher ETDE than either weightlifters or controls (p < 0.05). Binomial logistic regression identified longitudinal systolic velocity < 9 cm s" 1 and ETDE velocity < 11 cm s" 1 as the best combination of variables to predict pathological increases in heart size. Study two examined older subjects in order to determine whether the criteria set out in study one were applicable to senior athletes. The subject groups were the same as in study one however all subjects were aged between 36-55. In this case systolic annular velocity was significantly lower in groups with pathological LVH but ETDE < 9 cm s" 1 was a better differentiator. Binomial logistic regression identified ETDE < 9 cm s" 1 and a mitral E / A ratio < 1 as the best combination of variables to predict pathological LVH. Study three examined the age related changes in long axis function using the pooled data from studies one and two. This demonstrated that in the pathological LVH groups only ETDE / ATDE ratio was significantly correlated with age (r = - 0.5 p < 0.05) suggesting that there appears to be no summation of the effects of pathology and age on mitral annular velocities. The control groups demonstrated a significant age related reduction in all long axis variables (systolic velocity r = - 0.7 p < 0.05; ETDE r = - 0.6 p < 0.01; ATDE r = 0.5 p < 0.05; ETD E / ATDE r = - 0.5 p< 0.01). Weightlifters however did not demonstrate an age related decline in either systolic or diastolic annular velocities. Runners had no age related decline in systolic annular velocities, and whilst they had an age dependent fall in ETDE ( r = - 0.62 p < 0.05) the older runners ETDE were still significantly faster (p < 0.05) than that seen in control subjects. Study four investigated relationship between mitral annular velocity and VOiruK in runners, weightlifters and controls. These results demonstrated peak exercise E TDE strongly correlated to VO^PEAK (r = 0.8 p < 0.01). ConclusionsTaken together these data suggest that longitudinal velocities of the mitral annulus may be useful in determining the nature of increases in heart size, in addition the increased performance of endurance - trained athletes is due in part to functional changes of the long axis.

Made available in DSpace on 2015-07-22T20:50:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-03-25. Added 1 bitstream(s) on 2015-08-11T03:25:40Z : No. of bitstreams: 1 Publico-057a.pdf: 1544247 bytes, checksum: d76c2d7c07bfd1b50436489da9d22288 (MD5). Added 1 bitstream(s) on 2015-08-11T03:25:40Z : No. of bitstreams: 2 Publico-057a.pdf: 1544247 bytes, checksum: d76c2d7c07bfd1b50436489da9d22288 (MD5) Publico-057b.pdf: 1030631 bytes, checksum: 9562ff77059213eafe1900cb95553c45 (MD5) / Objetivo:Estabelecer o diagnóstico da hipertrofia ventricular esquerda(HVE)em pacientes com doença renal crônica(DRC)em programa de hemodiálise(HD)por sete diferentes critérios eletrocardiográficos, assim como pela radiografia de tórax,correlacionando estes dois métodos propedêuticos com o índice de massa do ventrículo esquerdo (IMVE)obtido pelo ecocardiograma.Métodos:Estudo transversal que incluiu 100 pacientes(58 homens e 42 mulheres,idade média de 46,2 ± 14,0 anos)com DRC de todas as etiologias,há pelo menos seis meses em HD.Foram obtidos ecocardiograma,eletrocardiograma e radiografia de tórax dos pacientes,sempre até uma hora após o término das sessões de HD.Resultados:A HVE foi detectada em 83pacientes(83 por cento),dos quais 56 (67,4 por cento)apresentavam o padrão concêntrico e 27(32,6 por cento)o padrão excêntrico de HVE.O tempo médio dos pacientes em HD foi de 50,7 ± 46,5 meses, mediana de 33,5 meses.A média do IMVE foi de 154,9± 57,3 g/m2.Todos os métodos eletrocardiográficos estudados e o índice cardiotorácico(ICT)apresentaram sensibilidade,especificidade e acurácia diagnósticas acima de 50 por cento.Pela correlação linear de Pearson com o IMVE apenas o critério de Sokolow-Lyon voltagem não apresentou coeficiente ≥ 0,50.Já o cálculo da razão de verossimilhança mostrou que o tanto o ECG como a radiografia de tórax possuem poder discriminatório para diagnóstico de HVE na população estudada,com ênfase para os critérios de Cornell produto e Romhilt-Estes.Não houve correlação entre o IMVE com o intervalo QTc e sua dispersão.Conclusões:O eletrocardiograma e a radiografia de tórax são métodos seguros,úteis,eficazes e de alta reprodutibilidade no diagnósticode HVE dos pacientes em HD.A utilidade do ECG é realçada pela capacidade de detectar alterações eletrofisiológicas,como o intervalo QTc e sua dispersão. / Objective: To establish the diagnosis of left ventricular hypertrophy (LVH) in haemodialysis (HD) patients with chronic kidney disease (CKD) using seven different electrocardiographic criteria and chest radiography, and to correlate these two diagnostic methods with left ventricular mass index (LVMI) as obtained by echocardiogram. Methods: Cross-sectional study including 100 patients (58 men and 42 women, mean age of 46.2 ± 14.0 years) with CKD of all causes, undergoing HD for at least six months. Echocardiogram, electrocardiogram and chest radiography were obtained from all patients, always up to one hour after the end of the HD sessions. Results: LVH was detected in 83 patients (83%), of which 56 (67.4%) presented a concentric pattern and 27 (32.6%) an eccentric pattern of LVH. The patients had been undergoing HD for a mean time of 50.7 ± 46.5 months, median of 33,5 months. The mean LVMI was 154.9 ± 57.3 g/m2. All electrocardiographic methods studied and the cardiothoracic ratio (CTR) had diagnostic sensitivity, specificity and accuracy higher than 50%. Using Pearson’s linear correlation with LVMI, only the Sokolow-Lyon voltage criterion did not present a 0.50 coefficient. The calculation of the likelihood ratio, in turn, showed that both ECG and chest radiography have a discriminatory power for the diagnosis of LVH in the population studied, with emphasis on for the Cornell product and Romhilt-Estes criteria. No correlation was found between LVMI and QTc and QTc dispersion. Conclusions: Electrocardiogram and chest radiography are safe, useful, efficient and highly reproducible methods for the diagnosis of LVH in HD patients. The usefulness of ECG is stressed by its ability to detect electrophysiological changes such as QTc and QTc dispersion. / TEDE / BV UNIFESP: Teses e dissertações