Cette thèse porte sur le problème du ballottement d'un liquide dans un réservoir, rencontré dans le transport et le stockage du GNL par des structures flottantes. La prédiction des chargements réels, dus au ballotement sur les parois du réservoir, est souvent basée sur des études expérimentales à petite échelle. La modélisation expérimentale à petite échelle respecte la similitude de Froude et le rapport de densité entre le gaz et le liquide. Cependant, d’autres similitudes sont biaisées comme la similitude par rapport au nombre de Weber et la similitude par rapport au nombre de Reynolds. De plus, les pressions enregistrées montrent une grande variabilité quand le même essai est répété. Dans une première partie, différentes sources physiques responsables de cette variabilité sont discutées, à savoir les instabilités de surface libre, la retombée des gouttes et des jets liquides sur la surface libre, et la production et l'entraînement des bulles dans le liquide. En fait, ces phénomènes sont à l'origine des perturbations de l'écoulement, de la variabilité de la géométrie de la vague et de cette façon des pressions engendrées par cette dernière sur la paroi. D'autres mécanismes de dissipation d’énergie sont identifiés. Ils sont liés aux frottements aux parois et aux déferlements de vagues. Nous montrons que cette dissipation induit un effet mémoire à courte durée pour l’écoulement, permettant de reproduire pour chaque impact la distribution statistique des pics de pression avec une courte durée des excitations. Ces sources de variabilité et ces mécanismes de dissipation dépendent de la tension de surface et de la viscosité du liquide. Ainsi nous étudions dans une deuxième partie, les effets de ces paramètres physiques. Nous montrons que la forme locale de la vague dépend de la tension de surface. Par contre, les effets sur la forme globale de la vague sont négligeables. Plus la tension de surface diminue, plus les pics pression sont faibles. Ce qui est dû aux différents phénomènes liés au développement des ligaments, la fragmentation en gouttes et la génération de la mousse sur la crête de la vague, et à l’entraînement des bulles dans le liquide. Quant à la viscosité du liquide, elle affecte à la fois la forme globale et la forme locale de la vague, là encore les pressions sont modifiées. Cette étude paramétrique permet, dans une troisième partie, d'étudier et comprendre les effets du nombre de Weber et du nombre de Reynolds, en comparant les résultats pour deux échelles différentes 1:40 et 1:20, quand les mêmes fluides sont considérés. De plus, en se basant sur différents cas de comparaison avec la similitude de Reynolds et/ou la similitude de Weber, nous montrons que la double similitude est indispensable pour obtenir une forme de vague avant l'impact indépendante de l'échelle. Cependant, la distribution statistique des pics de pression dépend aussi d’autres nombres adimensionnels à savoir le nombre de Mach du liquide et le nombre de Mach du gaz. / This work focuses on sloshing problem, encountered in the transport and storage of LNG by floating structures. The prediction of real sloshing loads is often based on small-scale experimental studies, respecting the Froude similarity and the density ratio between the gas and the liquid. However, other similarities are biased such as the Weber similarity and the Reynolds similarity. In addition, the recorded pressures show great variability when the same test is repeated. In a first part, different physical sources responsible for this variability are discussed, which are the free surface instabilities, the falling droplets and liquid jets impinging on the free surface, and the liquid entrainment by bubbles. In fact, these phenomena are at the origin of the flow disturbances, the variability of the wave shape, and hence its pressures on the wall. Other dissipation mechanisms are identified. They are related to wall frictions and breaking waves. Thanks to this energy dissipation, we show that the flow is characterized by a short-term memory, making it possible to reproduce for each impact its statistical distribution of pressure peaks with a short duration of excitations. These sources of variability and dissipation mechanisms depend on the surface tension and the viscosity of the liquid. Thus, we study, in a second part, these physical parameters. We show that the local wave shape depends on the surface tension. However, its effects on the global wave shape are negligible. Besides, when the surface tension is reduced, the statistical pressures are reduced. This is due to various phenomena related to the development of liquid ligaments, their fragmentation into drops and the generation of foam at the wave crest, and the liquid entrainment by bubbles. As for the viscosity of the liquid, it affects both the local and global shape wave shapes, again the pressures are changed. Based on this parametric study, The effects of Weber number and Reynolds number are studied by comparing the results for two different scales 1:40 and 1:20, when the same fluids are used. Moreover, considering different cases of comparison with Reynolds number similarity and / or Weber number similarity, the results show that both similarities are essential to obtain a scaleindependent wave shape. However, the statistical distribution of pressure peaks also depends on other dimensionless numbers, namely the Mach number of the liquid and the Mach number of the gas.

An autonomic dysfunction caused by spinal cord injury may have a significant impact on quality of life, especially in cases of lesions occuring above the sixth spinal segment. In these cases also cardiovascular system control is damaged in a different extent, which is subsequently presented by e.g. persisting bradycardia, heart frequency inadequate reaction to strain and stress or by huge variations of blood pressure values, which the situation complicate even more. The fact that cardiovascular diseases take now the frontmost place in causes of mortality of people with spinal cord injury is another evidence how important this topic is. The main aim of my thesis was to describe impacts of autonomic injury on cardiovascular functions and to try to objectify them using heart rate and blood pressure variability. Twenty-one patients of Motol University Hospitalv Spinal Unit with spinal cord lesion above Th6 segment and ten healthy people as a control group participated in the study. We created suitable conditions for highlighting disrupted cardiovascular functions of urgent spinal patients by modification of the standardized Head Up Tilt Test (HUTT). The heart rate and blood pressure values were continuously monitored by Finapres device before, during and also after verticalization on a tilt table....

No description available.

A síncope neurocardiogênica (SNC) é caracterizada por perda transitória da consciência e do controle postural, devido a uma hipoperfusão cerebral global de surgimento abrupto, com recuperação rápida e espontânea do paciente ao retornar à posição horizontal. Entretanto, investigações adicionais são necessárias para melhor avaliação das respostas cardiorrespiratórias e autonômicas de pacientes com SNC submetidos ao Tilt-test. O presente estudo teve como objetivo avaliar, em pacientes com história clínica sugestiva de SNC, os efeitos da mudança postural induzidas pelo Tilt-test na pressão arterial (PA) e frequência cardíaca (FC), na variabilidade cardiocirculatória e na sensibilidade barorreflexa (SBR). Além disso, o estudo também avaliou a relação entre a idade, sexo e características antropométricas dos pacientes com as respostas ao Tilt-test, e a relação entre o tempo do início da mudança postural e o momento da síncope, com um ou mais parâmetros acima mencionados. O estudo foi dividido em 3 partes: 1 Estudo retrospectivo de 180 pacientes, com história clínica sugestiva de SNC, mas que apresentaram Tilt-test positivo (TTP) (128 indivíduos) ou negativo (TTN) (52 indivíduos) para síncope; 2 Estudo da variabilidade da frequência cardíaca (VFC), usando-se métodos lineares (Transformada Rápida de Fourier) em pacientes com história clínica sugestiva de SNC, e com respostas positiva ou negativa ao Tilt-test. Foram incluídos 62 pacientes, 31 com Tilt-test positivo e 31 negativo; 3 Estudo da variabilidade da pressão arterial sistólica (VPAS), usando-se métodos lineares (Transformada Rápida de Fourier), e da SBR (Método da Sequência) em pacientes com história clínica sugestiva de SNC, e com respostas positiva ou negativa ao Tilt-test. Foram estudados 33 indivíduos, 16 com Tilt-test positivo e 17 negativo. Estudo 1 Observou-se que a incidência de SNC foi 1,5 vezes maior em mulheres do que em homens. Além disso, os grupos TTP e TTN apresentaram idade e características antropométricas semelhantes entre si, e não houve significância estatística nas correlações entre o tempo do início da posição vertical até a síncope, a idade e as características antropométricas. Estudo 2 Comparando os 2 grupos nos domínios do tempo (SD-iRR, variância-iRR, RMSSD) e da frequência (LF (un), HF (un) e LF/HF) nas fases Pré-Tilt, Tilt e Pós-Tilt, com exceção do iRR (ms), não observou-se diferença entre os grupos. Houve, na fase Tilt, um menor valor do iRR no grupo TTP. O Pré-Tilt comparado ao Tilt, promoveu em ambos os grupos redução do iRR e aumento na razão LF/HF. Estudo 3 Comparando-se os grupos TTP e TTN no Pré-Tilt e Tilt, não houve diferença no LF da PAS e na SBR. O Tilt promoveu, em ambos os grupos, aumento no LF da PAS, redução na SBR. Somente no grupo TTP foi observado aumento no desvio padrão da PAS durante o Tilt. Em conclusão, o estudo 1 demonstrou que a SNC não foi influenciada pela idade e características antropométricas, no que diz respeito à prevalência, e ao tempo de duração entre o início da mudança postural no Tilt-test e o momento do aparecimento da síncope na posição vertical. O estudo 2 demonstrou que indivíduos com suspeita clínica de SNC, e Tilt-test positivo ou negativo não apresentam anormalidades no balanço simpato-vagal cardíaco, mas, apresentaram diferenças no iRR. O estudo 3 não evidenciou diferenças no controle autonômico cardiovascular (LF-PAS e SBR) entre os grupos TTP e TTN no Pré-Tilt e Tilt. Os estudos 2 e 3 mostraram que com a metodologia utilizada na análise da VFC e VPAS não foi possível detectar anormalidades significativas da modulação autonômica cardiovascular nos grupos TTP e TTN, e desse modo, prever na posição vertical do Tilttest, se um paciente com história clínica sugestiva de SNC apresentará ou não síncope. / Neurocardiogenic syncope (NCS) is characterized by transient loss of consciousness and postural control, due to abrupt global cerebral hypoperfusion, with rapid and spontaneous recovery after changing the patient to horizontal position. However, further investigations are necessary to better understand the cardiorespiratory and autonomic responses to the Tilt-test in NCS patients. The present study aimed to evaluate, in patients with a history suspicion of NCS, the effects of postural change (Tilt-test) on blood pressure (BP) and heart rate (HR), on the cardiovascular variability and baroreflex sensitivity (BRS). Furthermore, the study also assessed the relationship between age, sex and anthropometric characteristics with the Tilt-test responses, and the relationship between the time period taken to experience syncope following postural change and the above cited parameters. The study was divided into three parts: 1 A retrospective study with 180 patients with a history suspicion of NCS, that experienced (TTP; 128 individuals) or not (TTN; 52 individuals) syncope following Tilt-test; 2 A study of the heart rate variability (HRV), assessed by linear methods (Fast Fourier Transform), in patients with a history suspicion of NCS and that experienced, or not, syncope following Tilt-test. The study included 62 patients (31 in TTP group and 31 in TTN group); 3 A study of the systolic blood pressure variability (SAPV), using linear methods (Fast Fourier Transform), and of the BRS (Sequence Method) in patients with a history compatible with NCS and that experienced, or not, syncope following Tilt-test. The study included 33 patients (16 in TTP group and 17 in TTN group). Study 1 it was observed that the incidence of NCS was 1.5 times greater in women than in men. Furthermore, groups TTP and TTN showed age and anthropometric characteristics similar to each other and no statistical significance was observed in the correlations among the time period taken to experience syncope following postural change and age and anthropometric characteristics. Study 2 The analysis of the cardiovascular variability, by means of time (SD-iRR, variance-iRR, RMSSD) and frequency (LF (nu), HF (nu) and LF/HF) domain methods, revealed no differences between groups in the Pre-Tilt, Tilt and Post-Tilt phases. However, iRR (ms) was found different between groups. During the Tilt phase, TTP group has shown lower iRR as compared to TTN. Also, TTP and TTN groups exhibited lower iRR and higher LF/HF ratio during Tilt-test as compared to Pre-Tilt phase. Study 3 Comparing the TTP and TTN groups, no statistical differences were found in the LF power of SAP and BRS in both Pre-Tilt and Tilt phases. Following Tilt-test it was observed an increase in LF power of SAP and a reduction in BRS. TTP group showed higher SAP standard deviation during the Tilt phase. In conclusion, study 1 demonstrated that NCS incidence and the time period taken to experience syncope following postural change were not influenced by age and anthropometric characteristics. Study 2 has shown that patients with a history suspicion of NCS, that experienced or not syncope following Tilt-test do not show abnormalities in the sympatovagal balance, but exhibited changes in the iRR. Study 3 showed that the cardiovascular autonomic control (LF-SAP and BRS) is not different between the TTP and TTN groups, in the Pre-Tilt and Tilt phases. Studies 2 and 3 have shown that the methods employed in the analysis of HRV and SAPV were unable to reveal abnormalities in the cardiovascular autonomic modulation in TTP and TTN groups, and thus, can not predict if a patient with a history suspicion of NCS will experience or not syncope during Tilt-test.

INTRODUÇÂO: A hipertensão arterial sistêmica (HAS) é uma condição clínica com alta prevalência, sendo considerada como o principal fator de risco modificável para o desenvolvimento de insuficiência cardíaca (IC). Dentre os mecanismos relacionados à progressão da HAS para a IC, a hiperatividade simpática e a disfunção endotelial devem ser consideradas. OBJETIVO: Avaliar a modulação do sistema nervoso autônomo (central e periférico), e a função endotelial em pacientes hipertensos com diferentes graus de disfunção diastólica (DD) do ventrículo esquerdo (VE). CASUÍSTICA E MÉTODO: Quarenta e cinco pacientes com HAS, sem outras co-morbidades foram submetidos ao exame de ecoDopplercardiograma tecidual, e foram alocados em três grupos: (GHT) sem alteração funcional ou estrutural cardíacas (n=15, 7 homens, 48±2 anos, IMC 28±1 Kg/m2), (GDD-ar) com diagnóstico prévio de IC diastólica e com DD padrão alteração de relaxamento do VE (n=15, 7 homens, 53±2 anos, IMC 29±1 Kg/m2) e (GDD-pr) com diagnóstico prévio de IC diastólica com padrão pseudonormal ou restritivo de DD do VE (n=15, 9 homens, 51±2 anos, IMC 27±1 Kg/m2). Voluntários saudáveis normotensos (n=14, grupo GNT) pareados para idade, sexo e IMC também foram avaliados. Curvas de pressão arterial (PA) foram registradas de modo contínuo e não invasivo (Finometer®) durante 15 minutos em repouso, na posição supina. Simultaneamente, a atividade nervosa simpática muscular (ANSM) foi registrada por meio da técnica de microneurografia. A variabilidade da freqüência cardíaca (VFC) e da pressão arterial sistólica (VPAS) foi estimada pelo método FFT. Em um segundo momento foi realizada a avaliação da função endotelial, por meio de ultrassonografia da artéria braquial associada à manobra de hiperemia reativa e após administração de trinitrato sublingual. As análises estatísticas foram realizadas pelo teste exato de Fisher e ANOVA, os resultados expressos em média ± erro padrão ou em mediana (valores mínimos e máximos). RESULTADOS: Não houve diferenças de gênero, idade e IMC entre os grupos, como também no uso das diferentes classes de drogas anti-hipertensivas entre os hipertensos. Os parâmetros estruturais cardíacos foram semelhante entre os grupos, com exceção da massa de VE do grupo GDD-pr [98 (66-162) g/m2] foi maior, p<0,05, quando comparada ao grupo GNT [85 (56-95) g/m2]. A PA sistólica (PAS) não foi diferente entre GHT, GDD-ar e GDD-pr [(138 (110-149), 133 (104-190) e 148 (118-171) mmHg, respectivamente]. Os grupos GDD-ar e GDD-pr apresentaram PAS maiores, p<0,05,quando comparados ao grupo GNT [121(108-133) mmHg]. A PA diastólica foi semelhante entre os grupos. Os grupos mostraram semelhantes valores para a modulação autonômica cardíaca avaliada pela VFC. A modulação simpática periférica representada pelo componente LF PAS da VPAS (mmHg2) foi aumentada nos grupos GDD-ar (12,2±1,3) e GDD-pr (11,7±1,2) quando comparados ao grupo GNT (6,7±0,6), p<0,05, mas não quando comparada ao grupo GHT (9,3±1,1). O prejuízo baroreflexo (índice alfa LF, ms/mmHg) foi observado nos grupos GDD-ar (4,6±0,6) e GDD-pr (5,07±0,7) quando comparados ao grupo GNT (8,2±1), p<0,05, mas não quando comparados ao grupo GHT (6,05±0,5). ANSM (espículas/min) foi maior significativamente nos grupos GDD-ar (33±1) e GDD-pr (32±1) quando comparada aos grupos GHT (26±1) e GNT (15±1) p<0,05. Ainda, o grupo GHT apresentou aumento da ANSM quando comparado ao grupo GNT, p<0,05. Os grupo GDD-ar e GDD-pr apresentaram valores semelhantes de ANSM. Com relação à avaliação da função endotelial, os grupos hipertensos apresentaram menor dilatação dependente do endotélio, sendo que somente no grupo GDD-ar [0,67 (0,0-8,7)%] houve significância estatística quando comparado ao GNT [6,3 (2,6-8,2)%]. Na avaliação da vasodilatação independente do endotélio os grupos apresentaram respostas semelhantes. CONCLUSÃO: A presença de disfunção diastólica, em qualquer grau, está associada à maior ANSM e modulação simpática periférica (LF PAS) e a menor sensibilidade do baroreflexo. A modulação simpática cardíaca não apresentou diferença entre os grupos em repouso. Outros estudos são necessários para esclarecer a relação entre causa - efeito de tais achados / INTRODUTION: The hypertension (HP) is a clinical condition with high prevalence, considered as a main modifiable risk factor for developing heart failure (HF). Among the mechanism related to the progression for HP to the HF, the sympathetic hyperactivity and endothelial dysfunction should be considered. OBJECTIVE: Evaluate the autonomic nervous system modulation (central and peripheral), and endothelial function in hypertensive patients with different pattern of diastolic dysfunction (DD) of the left ventricle (LV). METHOD: Forty-five hypertensive patients without comorbities were submitted to tissue Doppler echocardiography and allocated into three groups: (GHT) without cardiac functional or structural abnormalities (n=15, 7 men, 48±2 years, BMI 28±1 Kg/m2); (GDD-ar) with prior diastolic HF and impaired relaxation pattern of DD of LV (n=15, 7 men, 53±2 years, BMI 29±1 Kg/m2), and (GDD-pr) with prior diastolic HF and pseudonormal and restrictive patterns of DD of LV (n=15, 9 men, 51±2 years, BMI 27±1 Kg/m2). Normotensive healthy volunteers matched for age, sex and body mass index were also evaluated. Curves of blood pressure (BP) were recorded non-invasively and continuously (Finometer®) for 15 minutes at rest in the supine position. Simultaneously, muscle nerve sympathetic activity (MNSA) was recorded by microneurography technique. The heart rate and systolic blood pressure variability (HRV and SPBV) was estimated by FFT method. Afterwards, an evaluation of endothelial function through brachial artery ultrasound maneuver associated with reactive hyperemia and after sublingual administration of trinitrate was conducted. Statistical analysis was performed by Fishers exact test and ANOVA, the results are expressed as mean±standard deviation or median (minimum and maximum values). RESULTS: There were no differences in gender, age and BMI between the groups, as well as in the use of different classes of antihypertensive drugs among hypertensive patients. Cardiac structural parameters were similar between groups, except for LV mass in GDD-pr group [98 (66-162) g/m2] which was higher, p<0.05, when compared to the GNT group [85 (56-95) g/m2]. The systolic blood pressure (SBP) was similar between GHT, GDD-ar and GDD-pr groups [(138 (110-149), 133 (104-190) e 148 (118-171) mmHg, respectively]. The GDD-ar and GDD-pr groups had higher SBP, p<0.05, when compared to GNT group [121(108-133) mmHg]. The diastolic BP was similar between groups. The groups showed similar values for cardiac autonomic modulation assessed by HRV. The peripheral sympathetic modulation represented by the LF component of SBP (SBPV, mmHg2) was increased in GDD-ar group (12,2±1,3) and GDD-pr group (11,7±1,2) compared to the GNT group (6,7±0,6), p<0.05, but not when compared to GHT group (9,3±1,1). The impairment of the baroreflex (LF alpha índex, ms/mmHg) was observed in the GDD-ar (4,6±0,6) e GDD-pr (5,07±0,7) groups compared to the GNT group (8,2±1), p<0.05, but not when compared to GHT group (6,05±0,5). MNSA (burst/min) was significantly higher in GDD-ar (33±1) e GDD-pr (32±1) groups compared to GHT group (26±1) and GNT group (15±1) p<0.05. Also the GHT group showed increased MNSA when compared to GNT group, p<0.05. The GDD-ar and GDD-pr groups showed similar values of MNSA. Regarding the assessment of endothelial function, hypertensive groups had lower endothelium-dependent dilatation, but only in GDD-ar group [0,67 (0,0-8,7)%] was statistically significant when compared to GNT group [6,3 (2,6-8,2)%]. In the evaluation of endothelium-independent vasodilatation all groups showed similar responses. CONCLUSION: The presence of diastolic dysfunction of any pattern is associated with higher MNSA and peripheral sympathetic modulation (LF SBP) and lower sensitivity of the baroreflex. Cardiac sympathetic modulation did not differ between groups at rest. Further studies are needed to clarify the relationship between cause-effect of such findings

INTRODUÇÂO: A hipertensão arterial sistêmica (HAS) é uma condição clínica com alta prevalência, sendo considerada como o principal fator de risco modificável para o desenvolvimento de insuficiência cardíaca (IC). Dentre os mecanismos relacionados à progressão da HAS para a IC, a hiperatividade simpática e a disfunção endotelial devem ser consideradas. OBJETIVO: Avaliar a modulação do sistema nervoso autônomo (central e periférico), e a função endotelial em pacientes hipertensos com diferentes graus de disfunção diastólica (DD) do ventrículo esquerdo (VE). CASUÍSTICA E MÉTODO: Quarenta e cinco pacientes com HAS, sem outras co-morbidades foram submetidos ao exame de ecoDopplercardiograma tecidual, e foram alocados em três grupos: (GHT) sem alteração funcional ou estrutural cardíacas (n=15, 7 homens, 48±2 anos, IMC 28±1 Kg/m2), (GDD-ar) com diagnóstico prévio de IC diastólica e com DD padrão alteração de relaxamento do VE (n=15, 7 homens, 53±2 anos, IMC 29±1 Kg/m2) e (GDD-pr) com diagnóstico prévio de IC diastólica com padrão pseudonormal ou restritivo de DD do VE (n=15, 9 homens, 51±2 anos, IMC 27±1 Kg/m2). Voluntários saudáveis normotensos (n=14, grupo GNT) pareados para idade, sexo e IMC também foram avaliados. Curvas de pressão arterial (PA) foram registradas de modo contínuo e não invasivo (Finometer®) durante 15 minutos em repouso, na posição supina. Simultaneamente, a atividade nervosa simpática muscular (ANSM) foi registrada por meio da técnica de microneurografia. A variabilidade da freqüência cardíaca (VFC) e da pressão arterial sistólica (VPAS) foi estimada pelo método FFT. Em um segundo momento foi realizada a avaliação da função endotelial, por meio de ultrassonografia da artéria braquial associada à manobra de hiperemia reativa e após administração de trinitrato sublingual. As análises estatísticas foram realizadas pelo teste exato de Fisher e ANOVA, os resultados expressos em média ± erro padrão ou em mediana (valores mínimos e máximos). RESULTADOS: Não houve diferenças de gênero, idade e IMC entre os grupos, como também no uso das diferentes classes de drogas anti-hipertensivas entre os hipertensos. Os parâmetros estruturais cardíacos foram semelhante entre os grupos, com exceção da massa de VE do grupo GDD-pr [98 (66-162) g/m2] foi maior, p<0,05, quando comparada ao grupo GNT [85 (56-95) g/m2]. A PA sistólica (PAS) não foi diferente entre GHT, GDD-ar e GDD-pr [(138 (110-149), 133 (104-190) e 148 (118-171) mmHg, respectivamente]. Os grupos GDD-ar e GDD-pr apresentaram PAS maiores, p<0,05,quando comparados ao grupo GNT [121(108-133) mmHg]. A PA diastólica foi semelhante entre os grupos. Os grupos mostraram semelhantes valores para a modulação autonômica cardíaca avaliada pela VFC. A modulação simpática periférica representada pelo componente LF PAS da VPAS (mmHg2) foi aumentada nos grupos GDD-ar (12,2±1,3) e GDD-pr (11,7±1,2) quando comparados ao grupo GNT (6,7±0,6), p<0,05, mas não quando comparada ao grupo GHT (9,3±1,1). O prejuízo baroreflexo (índice alfa LF, ms/mmHg) foi observado nos grupos GDD-ar (4,6±0,6) e GDD-pr (5,07±0,7) quando comparados ao grupo GNT (8,2±1), p<0,05, mas não quando comparados ao grupo GHT (6,05±0,5). ANSM (espículas/min) foi maior significativamente nos grupos GDD-ar (33±1) e GDD-pr (32±1) quando comparada aos grupos GHT (26±1) e GNT (15±1) p<0,05. Ainda, o grupo GHT apresentou aumento da ANSM quando comparado ao grupo GNT, p<0,05. Os grupo GDD-ar e GDD-pr apresentaram valores semelhantes de ANSM. Com relação à avaliação da função endotelial, os grupos hipertensos apresentaram menor dilatação dependente do endotélio, sendo que somente no grupo GDD-ar [0,67 (0,0-8,7)%] houve significância estatística quando comparado ao GNT [6,3 (2,6-8,2)%]. Na avaliação da vasodilatação independente do endotélio os grupos apresentaram respostas semelhantes. CONCLUSÃO: A presença de disfunção diastólica, em qualquer grau, está associada à maior ANSM e modulação simpática periférica (LF PAS) e a menor sensibilidade do baroreflexo. A modulação simpática cardíaca não apresentou diferença entre os grupos em repouso. Outros estudos são necessários para esclarecer a relação entre causa - efeito de tais achados / INTRODUTION: The hypertension (HP) is a clinical condition with high prevalence, considered as a main modifiable risk factor for developing heart failure (HF). Among the mechanism related to the progression for HP to the HF, the sympathetic hyperactivity and endothelial dysfunction should be considered. OBJECTIVE: Evaluate the autonomic nervous system modulation (central and peripheral), and endothelial function in hypertensive patients with different pattern of diastolic dysfunction (DD) of the left ventricle (LV). METHOD: Forty-five hypertensive patients without comorbities were submitted to tissue Doppler echocardiography and allocated into three groups: (GHT) without cardiac functional or structural abnormalities (n=15, 7 men, 48±2 years, BMI 28±1 Kg/m2); (GDD-ar) with prior diastolic HF and impaired relaxation pattern of DD of LV (n=15, 7 men, 53±2 years, BMI 29±1 Kg/m2), and (GDD-pr) with prior diastolic HF and pseudonormal and restrictive patterns of DD of LV (n=15, 9 men, 51±2 years, BMI 27±1 Kg/m2). Normotensive healthy volunteers matched for age, sex and body mass index were also evaluated. Curves of blood pressure (BP) were recorded non-invasively and continuously (Finometer®) for 15 minutes at rest in the supine position. Simultaneously, muscle nerve sympathetic activity (MNSA) was recorded by microneurography technique. The heart rate and systolic blood pressure variability (HRV and SPBV) was estimated by FFT method. Afterwards, an evaluation of endothelial function through brachial artery ultrasound maneuver associated with reactive hyperemia and after sublingual administration of trinitrate was conducted. Statistical analysis was performed by Fishers exact test and ANOVA, the results are expressed as mean±standard deviation or median (minimum and maximum values). RESULTS: There were no differences in gender, age and BMI between the groups, as well as in the use of different classes of antihypertensive drugs among hypertensive patients. Cardiac structural parameters were similar between groups, except for LV mass in GDD-pr group [98 (66-162) g/m2] which was higher, p<0.05, when compared to the GNT group [85 (56-95) g/m2]. The systolic blood pressure (SBP) was similar between GHT, GDD-ar and GDD-pr groups [(138 (110-149), 133 (104-190) e 148 (118-171) mmHg, respectively]. The GDD-ar and GDD-pr groups had higher SBP, p<0.05, when compared to GNT group [121(108-133) mmHg]. The diastolic BP was similar between groups. The groups showed similar values for cardiac autonomic modulation assessed by HRV. The peripheral sympathetic modulation represented by the LF component of SBP (SBPV, mmHg2) was increased in GDD-ar group (12,2±1,3) and GDD-pr group (11,7±1,2) compared to the GNT group (6,7±0,6), p<0.05, but not when compared to GHT group (9,3±1,1). The impairment of the baroreflex (LF alpha índex, ms/mmHg) was observed in the GDD-ar (4,6±0,6) e GDD-pr (5,07±0,7) groups compared to the GNT group (8,2±1), p<0.05, but not when compared to GHT group (6,05±0,5). MNSA (burst/min) was significantly higher in GDD-ar (33±1) e GDD-pr (32±1) groups compared to GHT group (26±1) and GNT group (15±1) p<0.05. Also the GHT group showed increased MNSA when compared to GNT group, p<0.05. The GDD-ar and GDD-pr groups showed similar values of MNSA. Regarding the assessment of endothelial function, hypertensive groups had lower endothelium-dependent dilatation, but only in GDD-ar group [0,67 (0,0-8,7)%] was statistically significant when compared to GNT group [6,3 (2,6-8,2)%]. In the evaluation of endothelium-independent vasodilatation all groups showed similar responses. CONCLUSION: The presence of diastolic dysfunction of any pattern is associated with higher MNSA and peripheral sympathetic modulation (LF SBP) and lower sensitivity of the baroreflex. Cardiac sympathetic modulation did not differ between groups at rest. Further studies are needed to clarify the relationship between cause-effect of such findings

A síncope neurocardiogênica (SNC) é caracterizada por perda transitória da consciência e do controle postural, devido a uma hipoperfusão cerebral global de surgimento abrupto, com recuperação rápida e espontânea do paciente ao retornar à posição horizontal. Entretanto, investigações adicionais são necessárias para melhor avaliação das respostas cardiorrespiratórias e autonômicas de pacientes com SNC submetidos ao Tilt-test. O presente estudo teve como objetivo avaliar, em pacientes com história clínica sugestiva de SNC, os efeitos da mudança postural induzidas pelo Tilt-test na pressão arterial (PA) e frequência cardíaca (FC), na variabilidade cardiocirculatória e na sensibilidade barorreflexa (SBR). Além disso, o estudo também avaliou a relação entre a idade, sexo e características antropométricas dos pacientes com as respostas ao Tilt-test, e a relação entre o tempo do início da mudança postural e o momento da síncope, com um ou mais parâmetros acima mencionados. O estudo foi dividido em 3 partes: 1 Estudo retrospectivo de 180 pacientes, com história clínica sugestiva de SNC, mas que apresentaram Tilt-test positivo (TTP) (128 indivíduos) ou negativo (TTN) (52 indivíduos) para síncope; 2 Estudo da variabilidade da frequência cardíaca (VFC), usando-se métodos lineares (Transformada Rápida de Fourier) em pacientes com história clínica sugestiva de SNC, e com respostas positiva ou negativa ao Tilt-test. Foram incluídos 62 pacientes, 31 com Tilt-test positivo e 31 negativo; 3 Estudo da variabilidade da pressão arterial sistólica (VPAS), usando-se métodos lineares (Transformada Rápida de Fourier), e da SBR (Método da Sequência) em pacientes com história clínica sugestiva de SNC, e com respostas positiva ou negativa ao Tilt-test. Foram estudados 33 indivíduos, 16 com Tilt-test positivo e 17 negativo. Estudo 1 Observou-se que a incidência de SNC foi 1,5 vezes maior em mulheres do que em homens. Além disso, os grupos TTP e TTN apresentaram idade e características antropométricas semelhantes entre si, e não houve significância estatística nas correlações entre o tempo do início da posição vertical até a síncope, a idade e as características antropométricas. Estudo 2 Comparando os 2 grupos nos domínios do tempo (SD-iRR, variância-iRR, RMSSD) e da frequência (LF (un), HF (un) e LF/HF) nas fases Pré-Tilt, Tilt e Pós-Tilt, com exceção do iRR (ms), não observou-se diferença entre os grupos. Houve, na fase Tilt, um menor valor do iRR no grupo TTP. O Pré-Tilt comparado ao Tilt, promoveu em ambos os grupos redução do iRR e aumento na razão LF/HF. Estudo 3 Comparando-se os grupos TTP e TTN no Pré-Tilt e Tilt, não houve diferença no LF da PAS e na SBR. O Tilt promoveu, em ambos os grupos, aumento no LF da PAS, redução na SBR. Somente no grupo TTP foi observado aumento no desvio padrão da PAS durante o Tilt. Em conclusão, o estudo 1 demonstrou que a SNC não foi influenciada pela idade e características antropométricas, no que diz respeito à prevalência, e ao tempo de duração entre o início da mudança postural no Tilt-test e o momento do aparecimento da síncope na posição vertical. O estudo 2 demonstrou que indivíduos com suspeita clínica de SNC, e Tilt-test positivo ou negativo não apresentam anormalidades no balanço simpato-vagal cardíaco, mas, apresentaram diferenças no iRR. O estudo 3 não evidenciou diferenças no controle autonômico cardiovascular (LF-PAS e SBR) entre os grupos TTP e TTN no Pré-Tilt e Tilt. Os estudos 2 e 3 mostraram que com a metodologia utilizada na análise da VFC e VPAS não foi possível detectar anormalidades significativas da modulação autonômica cardiovascular nos grupos TTP e TTN, e desse modo, prever na posição vertical do Tilttest, se um paciente com história clínica sugestiva de SNC apresentará ou não síncope. / Neurocardiogenic syncope (NCS) is characterized by transient loss of consciousness and postural control, due to abrupt global cerebral hypoperfusion, with rapid and spontaneous recovery after changing the patient to horizontal position. However, further investigations are necessary to better understand the cardiorespiratory and autonomic responses to the Tilt-test in NCS patients. The present study aimed to evaluate, in patients with a history suspicion of NCS, the effects of postural change (Tilt-test) on blood pressure (BP) and heart rate (HR), on the cardiovascular variability and baroreflex sensitivity (BRS). Furthermore, the study also assessed the relationship between age, sex and anthropometric characteristics with the Tilt-test responses, and the relationship between the time period taken to experience syncope following postural change and the above cited parameters. The study was divided into three parts: 1 A retrospective study with 180 patients with a history suspicion of NCS, that experienced (TTP; 128 individuals) or not (TTN; 52 individuals) syncope following Tilt-test; 2 A study of the heart rate variability (HRV), assessed by linear methods (Fast Fourier Transform), in patients with a history suspicion of NCS and that experienced, or not, syncope following Tilt-test. The study included 62 patients (31 in TTP group and 31 in TTN group); 3 A study of the systolic blood pressure variability (SAPV), using linear methods (Fast Fourier Transform), and of the BRS (Sequence Method) in patients with a history compatible with NCS and that experienced, or not, syncope following Tilt-test. The study included 33 patients (16 in TTP group and 17 in TTN group). Study 1 it was observed that the incidence of NCS was 1.5 times greater in women than in men. Furthermore, groups TTP and TTN showed age and anthropometric characteristics similar to each other and no statistical significance was observed in the correlations among the time period taken to experience syncope following postural change and age and anthropometric characteristics. Study 2 The analysis of the cardiovascular variability, by means of time (SD-iRR, variance-iRR, RMSSD) and frequency (LF (nu), HF (nu) and LF/HF) domain methods, revealed no differences between groups in the Pre-Tilt, Tilt and Post-Tilt phases. However, iRR (ms) was found different between groups. During the Tilt phase, TTP group has shown lower iRR as compared to TTN. Also, TTP and TTN groups exhibited lower iRR and higher LF/HF ratio during Tilt-test as compared to Pre-Tilt phase. Study 3 Comparing the TTP and TTN groups, no statistical differences were found in the LF power of SAP and BRS in both Pre-Tilt and Tilt phases. Following Tilt-test it was observed an increase in LF power of SAP and a reduction in BRS. TTP group showed higher SAP standard deviation during the Tilt phase. In conclusion, study 1 demonstrated that NCS incidence and the time period taken to experience syncope following postural change were not influenced by age and anthropometric characteristics. Study 2 has shown that patients with a history suspicion of NCS, that experienced or not syncope following Tilt-test do not show abnormalities in the sympatovagal balance, but exhibited changes in the iRR. Study 3 showed that the cardiovascular autonomic control (LF-SAP and BRS) is not different between the TTP and TTN groups, in the Pre-Tilt and Tilt phases. Studies 2 and 3 have shown that the methods employed in the analysis of HRV and SAPV were unable to reveal abnormalities in the cardiovascular autonomic modulation in TTP and TTN groups, and thus, can not predict if a patient with a history suspicion of NCS will experience or not syncope during Tilt-test.

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2018-07-19T19:15:24Z No. of bitstreams: 1 Mário César Nascimento.pdf: 1745805 bytes, checksum: ad4c8a4e2dc9ca8de775e2bd0ca30068 (MD5) / Made available in DSpace on 2018-07-19T19:15:24Z (GMT). No. of bitstreams: 1 Mário César Nascimento.pdf: 1745805 bytes, checksum: ad4c8a4e2dc9ca8de775e2bd0ca30068 (MD5) Previous issue date: 2017-12-15 / The objective of the present study was to evaluate the impact of the level of physical activity and overweight in offspring of normotensives or hypertensives, as well as to validate a scale of prediction of adherence to physical activity. This thesis was divided into two studies. In Study I, we observed that among the twenty items on the adherence scale, ten presented good reproducibility (Kappa> 0.70, Pearson's correlation> 0.81), good internal consistency (Cronbach's Alpha 0.84), good clarity and discriminant validity (p = 0.0006 vs sedentary, t = 4.12), correlation between the sum of the scale and the Mets (metabolic equivalent) evaluated by IPAQ with r = 0.073 and p = 0.048. In Study II, 114 males, young, physically active and insufficiently active adults, offspring of normotensives or hypertensives, overweight or eutrophic were selected. The IPAQ was used for the level of physical activity, the PSS-10 for perceived stress, the WHOQOL for quality of life analysis. Anthropometric, hematological and biochemical analyzes and systemic oxidative stress evaluations were performed. In addition, blood pressure (BP) recording beat-to-beat using the Finometer® was used for evaluation of hemodynamic parameters and of heart rate (HRV) and BP variability (BPV). The results showed a higher BMI and % of fat, both by folds and Bioelectrical impedance analysis, in the overweight groups compared to the eutrophic groups, as well as higher weekly caloric expenditure among the active groups in relation to the sedentary groups, independently of the familial history of hypertension (FHH). In the hematological and biochemical profile all groups presented values within the normal range. The BP values were similar between the studied groups, but a lower heart rate was observed in the active groups with a negative FHH. There was no difference in perceived stress levels, but the quality of life was better in the active groups, with lower benefits in the group with a positive FHH. In relation to HRV, the active eutrophic groups, both with a positive and negative FHH, had higher values of RMSSD (cardiac parasympathetic modulation) and lower sympatho/vagal balance in relation to their respective eutrophic sedentary groups, which was not observed in overweight groups. The groups with a positive FHH presented higher values of both simpato/vagal balance (eutrophic and overweight), SAP variance (just overweight) and vascular sympathetic modulation (LF) (eutrophic and overweight) compared to the group with negative FHH, and these differences were attenuated in the physically active group with FHH and overweight. The active eutrophic group with a negative FHH presented better baroreflex sensitivity in relation to their respective sedentary group, which was not observed in the group with a FHH. With regard to oxidative stress, active groups with a negative FHH had lower levels of hydrogen peroxide and nitrites and greater activity of the antioxidant enzyme glutathione peroxidase (just eutrophic) when compared to their respective sedentary groups, which was not observed for the offspring of hypertensives (sedentary vs actives). In addition, these two parameters and the oxidation of proteins (carbonyls) were increased in the overweight and non-overweight groups with a FHH in relation to the eutrophic group with a negative FHH, being attenuated in the active group with FHH and overweight. In conclusion, the scale of adherence to the physical active developed in this study showed good reproducibility, good internal consistency, clarity and discriminating validity. In addition, our results showed that even under normal clinical conditions, a positive FHH, regardless of the presence of overweight, induced autonomic dysfunction and increases in oxidative stress markers that may be precursors of cardiometabolic diseases in this genetically predisposed population. On the other hand, a physically active lifestyle improves HRV, baroreflex and parameters related to redox status in individuals with a negative FHH. Such benefits seem to be attenuated by the positive FHH, but a physically active lifestyle seems to prevent/attenuate the dysfunctions observed in this condition. / O objetivo do presente estudo foi avaliar o impacto do nível de atividade física e do sobrepeso em filhos de pais normotensos ou hipertensos, bem como validar uma escala de predição da aderência a atividade física. Esta tese foi dividida em dois estudos. No Estudo I, nossos resultados demonstram que entre os vinte itens da escala de aderência, dez apresentaram boa reprodutibilidade (Kappa > 0,70, correlação de Pearson >0,81), boa consistência interna (Alfa de Cronbach 0,84), boa clareza e validade discriminante (ativos p=<0,0006 vs. Sedentários; t= 4,12), Correlação entre o somatório da escala e o Mets (equivalente metabólico) avaliado pelo IPAQ com r=0,073 e p=0,048. No Estudo II, foram selecionados 114 sujeitos do sexo masculino, adultos jovens, fisicamente ativos e insuficientemente ativos, filhos biológicos de pais normotensos ou hipertensos, com sobrepeso ou eutróficos. Foram utilizados o IPAQ para o nível de atividade física, o PSS-10 para estresse percebido, e o WHOQOL para qualidade de vida. Foram realizadas análises antropométrica, hematológicas e bioquímicas sanguínea e de estresse oxidativo sistêmica, além de registro da pressão arterial (PA) batimento-a-batimento utilizando o Finometer® para avaliação de parâmetros hemodinâmicos e avaliação da variabilidade da frequência cardíaca (VFC) e da PA (VPA). Os resultados evidenciaram conforme esperado maior IMC e %G tanto por dobras quanto por bioimpedância, nos grupos com sobrepeso em relação aos eutróficos, bem como maior gasto calórico semanal entre os grupos ativos em relação aos grupos sedentários, independentemente do histórico familiar de hipertensão (HFH). No perfil hematológico e bioquímico sanguíneo todos os grupos apresentaram valores dentro da faixa de normalidade. Os valores de PA foram semelhantes entre os grupos estudados, porém foi observada menor frequência cardíaca nos grupos ativos com histórico negativo de hipertensão. Não houve diferença para níveis de estresse percebido, mas a qualidade de vida foi melhor nos grupos ativos, com menores benefícios no grupo com HFH positivo. Em relação a VFC, os grupos eutróficos ativos, tantos com HFH positivo quanto negativo, apresentaram valores maiores de RMSSD (modulação parassimpática cardíaca) e menores de balanço simpato/vagal em relação aos seus respectivos grupos sedentários eutróficos, o que não foi observado nos grupos com sobrepeso. Os grupos com HFH apresentaram maior balanço simpato/vagal que os eutróficos com HFH negativo. Quanto a VPA, os grupos com HFH positivo, eutrófico e com sobrepeso, apresentaram valores maiores tanto de variância de PAS quanto modulação simpática vascular (LF) em comparação ao grupo sem HFH, e essas diferenças foram atenuadas no grupo fisicamente ativo. O grupo de eutrófico ativo com HFH negativo apresentou melhor sensibilidade barorreflexa em relação ao seu respectivo grupo sedentário, o que não foi observado no grupo entre os sujeitos com HFH positivo. Com relação ao estresse oxidativo, os grupos ativos com HFH negativo apresentaram menores níveis de peróxido de hidrogênio e nitritos e maior atividade da enzima antioxidante glutationa peroxidase quando comparados aos seus respectivos grupos sedentários, o que não foi observado para os filhos de pais hipertensos. Além disto, estes dois parâmetros e a oxidação de proteínas (carbonilas) estavam aumentados nos grupos com e sem sobrepeso com HFH positivo em relação ao grupo eutrófico com HFH negativo, sendo atenuadas no grupo ativo com HFH positivo e sobrepeso. Em conclusão, a escala de aderência ao exercício desenvolvida neste estudo apresentou boa reprodutibilidade, boa consistência interna, clareza e validade descriminante. Além disto, os resultados evidenciam que mesmo sob condições clínicas de normalidade, o HFH positivo, independentemente da presença de sobrepeso, induz disfunção autonômica e aumento de marcadores de estresse oxidativo que podem ser precursores de doenças cardiometabólicas nesta população geneticamente predisposta. Por outro lado, um estilo de vida fisicamente ativo melhora a VFC, o baroreflexo e parâmetros relacionados ao estado redox em indivíduos com HFH negativo. Tais benefícios parecem atenuados pelo HFH positivo, mas um estilo de vida fisicamente ativo parece prevenir/atenuar as disfunções observadas nesta condição.

L’analyse spectrale de la fréquence cardiaque, de la pression artérielle systolique, de la pression artérielle diastolique ainsi que de la respiration par la transformée de Fourier rapide, est considérée comme une technique non invasive pour la détermination de l’activité du système nerveux autonome (SNA). Dans une population de sujets normaux volontaires, nous avons obtenu à l’état basal, des oscillations de basses fréquences (0,05-0,15Hz) reliées au système nerveux sympathique autonome et des oscillations de hautes fréquences (0,2Hz) représentant sur les intervalles entre chaque ondes R de l’électrocardiogramme (RR), l’arythmie sinusale respiratoire correspondant à une activité vagale. Nous avons comparé les tests de stimulation du système nerveux sympathique autonome déclenché par le passage de la position de repos (en décubitus dorsal), à la position orthostatique volontaire et le passage de la position de repos à la position orthostatique avec la table basculante à 60o. Nous avons également comparé un groupe normotendu à un groupe hypertendu qui a été soumis au passage du repos à l’orthostation volontaire et pour lesquels nous avons évalué la sensibilité du baroréflexe et la réponse sympathique par la mesure des catécholamines circulantes. Dans un groupe de sujets ayant une hypertension artérielle essentielle, nous avons évalué l’effet de la thérapie hypotensive, par le Trandolapril qui est un Inhibiteur de l’enzyme de conversion (IEC) de l`angiotensine. Dans ce groupe hypertendu, nous avons procédé, en plus de la stimulation sympathique par l’orthostation volontaire, à un exercice isométrique de trois minutes à 30 % de la force maximale. Nous avons également complété notre évaluation par la mesure de la densité de récepteurs ß2 adrénergiques sur lymphocytes et par la mesure des indices de contractilité à l’aide de l’échocardiographie en M mode. Les résultats ont montré, dans les groupes normaux volontaires, dans les deux types de stimulation du système nerveux sympathique par la position orthostatique, une augmentation significative des catécholamines plasmatiques avec une augmentation de la fréquence cardiaque et des basses fréquences de RR, confirmant ainsi que l’on est en état de stimulation sympathique. On observe en même temps une diminution significative des hautes fréquences de RR, suggérant un retrait vagal lors de cette stimulation. On a observé au test de la table basculante six cas d’hypotension orthostatique. On a comparé la position orthostatique volontaire entre le groupe de sujets normaux et le groupe de sujets hypertendus. L’analyse spectrale croisée de RR et de la pression artérielle systolique a permis d’évaluer dans l’hypertension artérielle (HTA), essentielle une sensibilité du baroréflexe atténuée, accompagnée d’une réactivité vagale réduite en présence d’une activité et d’une réactivité sympathique augmentées suggérant une altération sympathovagale dans l’HTA. Dans le groupe de sujets hypertendus traités (Trandolapril 2mg/jour), nous avons identifié un groupe de répondeurs au traitement par le Trandolapril et un groupe de non répondeurs à ce type de thérapie anti-hypertensive. Le groupe répondeur avait un profil hyper-adrénergique avec une hyper-réactivité sympathique, une fréquence cardiaque et des pressions artérielles diastolique et systolique plus élevées au repos. Dans le groupe total traité au Trandolapril, la densité des récepteurs ß2 adrénergiques a doublé, après thérapie, alors que la réactivité des basses fréquences obtenues à l’analyse spectrale a augmenté. Nous avons montré dans notre étude qu’un IECA a pu inhiber le mécanisme facilitateur de l’angII sur les terminaisons nerveuses sympathiques et a permis ainsi de réduire l’hyperactivité sympathique et le mécanisme de « down regulation » des récepteurs ß2 adrénergiques rendant ainsi l’expression de l’influence du SNA post synaptique plus efficace. Dans l’ensemble de nos protocoles cliniques, par l’utilisation de l’analyse spectrale des signaux RR, de la pression artérielle systolique,de la pression artérielle diastolique et de la respiration, nous avons montré que cette technique non invasive permet de décrire et de mieux comprendre les mécanismes physiologiques, physiopathologiques et pharmacologiques reliés au système nerveux autonome et à l’hypertension artérielle essentielle. / The spectral analysis of the heart rate, the systolic blood pressure, the diastolic blood pressure and the respiration with the Fast Fourier Transform, is considered as a non-invasive technique for the determination of the autonomic nervous system activity. In a population of normal volunteer subjects, we obtained in the basal state, low-frequency oscillations related to the sympathetic autonomous nervous system (0.05-0.15Hz) and the high-frequency oscillations (0.2Hz), which represent, on RR intervals, the respiratory sinus arrhythmia corresponding to vagal activity. We compared the sympathetic nervous system stimulation tests triggered by the transition from resting to voluntary orthostatic positions and the transition from resting to orthostatic position using tilt table at 60o. We also compared a normal blood pressure group to a hypertensive group which were both subject to the transition from resting to voluntary orthostation and for whom we evaluated the baroreflex sensitivity and the sympathetic response by measuring circulating catecholamines. In a group of subjects having an essential arterial hypertension, we have evaluated the effect of hypotensive therapy, by the Trandolapril which is an Angiotensin Converting Enzyme Inhibitor. In the hypertensive group, we evaluated the sympathetic stimulation using the voluntary orthostation, and we have also proceeded to a 3 minutes isometric exercise at 30% of maximum force. We have also completed our evaluation by measuring both the ß2 adrenergic receptor density on isolated lymphocytes and the contractility index using the echocardiography in M mode. In both sympathetic nervous system stimulation types by orthostatic position, the results have shown, for normal blood pressure volunteer subject groups, a significant increase in concentration of plasma catecholamines with an increase of heart rate (HR) and the low frequency RR, confirming therefore that we are in the presence of a sympathetic stimulation state. At the same time, we observed a significant decrease of high frequency of RR, suggesting a vagal withdrawal during the stimulation. We observed six cases of orthostatic hypotension from the tilt table test. We compared the voluntary orthostatic position between normal and hypertension subject groups. The results with combined spectral analysis of RR and the systolic blood pressure allowed to evaluate in the essential high blood pressure a reduced baroreflex sensitivity along with a reduced vagal reactivity in presence of increased sympathetic activity and reactivity suggesting a sympatho-vagal alteration in essential arterial hypertension. In hypertensive subjects treated with Trandolapril 2mg/day, we have identified a group responding to Trandolapril treatment and a group of non-responders to this type of anti-hypertensive therapy. The responding group has an hyper-adrenergic profile with higher sympathetic reactivity, heart rate and arterial diastolic and systolic pressures at rest. In the total group treated with Trandolapril, the ß2 adrenergic receptor density has doubled after therapy, while the reactivity of low frequencies obtained from spectral analysis has increased. We have shown in this study that Angiotensin Converting Enzyme Inhibitor could inhibit the facilitatory mechanism of angII on sympathetic nerve terminals and therefore allowed the reduction of the sympathetic hyperactivity and the cause of a beta2 adrenergic “down regulation”. Thus it allowed us to obtain an increased density of the receptors and the expression of more effective influence of post synaptic Sympathetic nervous system. In all of our clinical protocols, using spectral analysis of RR, systolic blood pressure, diastolic blood pressure and breathing signals, we have shown that this non-invasive technique has helped to describe and to better understand the physiological and pharmacological mechanisms related to the autonomic nervous system in normotensive and hypertensive subjects.

L’analyse spectrale de la fréquence cardiaque, de la pression artérielle systolique, de la pression artérielle diastolique ainsi que de la respiration par la transformée de Fourier rapide, est considérée comme une technique non invasive pour la détermination de l’activité du système nerveux autonome (SNA). Dans une population de sujets normaux volontaires, nous avons obtenu à l’état basal, des oscillations de basses fréquences (0,05-0,15Hz) reliées au système nerveux sympathique autonome et des oscillations de hautes fréquences (0,2Hz) représentant sur les intervalles entre chaque ondes R de l’électrocardiogramme (RR), l’arythmie sinusale respiratoire correspondant à une activité vagale. Nous avons comparé les tests de stimulation du système nerveux sympathique autonome déclenché par le passage de la position de repos (en décubitus dorsal), à la position orthostatique volontaire et le passage de la position de repos à la position orthostatique avec la table basculante à 60o. Nous avons également comparé un groupe normotendu à un groupe hypertendu qui a été soumis au passage du repos à l’orthostation volontaire et pour lesquels nous avons évalué la sensibilité du baroréflexe et la réponse sympathique par la mesure des catécholamines circulantes. Dans un groupe de sujets ayant une hypertension artérielle essentielle, nous avons évalué l’effet de la thérapie hypotensive, par le Trandolapril qui est un Inhibiteur de l’enzyme de conversion (IEC) de l`angiotensine. Dans ce groupe hypertendu, nous avons procédé, en plus de la stimulation sympathique par l’orthostation volontaire, à un exercice isométrique de trois minutes à 30 % de la force maximale. Nous avons également complété notre évaluation par la mesure de la densité de récepteurs ß2 adrénergiques sur lymphocytes et par la mesure des indices de contractilité à l’aide de l’échocardiographie en M mode. Les résultats ont montré, dans les groupes normaux volontaires, dans les deux types de stimulation du système nerveux sympathique par la position orthostatique, une augmentation significative des catécholamines plasmatiques avec une augmentation de la fréquence cardiaque et des basses fréquences de RR, confirmant ainsi que l’on est en état de stimulation sympathique. On observe en même temps une diminution significative des hautes fréquences de RR, suggérant un retrait vagal lors de cette stimulation. On a observé au test de la table basculante six cas d’hypotension orthostatique. On a comparé la position orthostatique volontaire entre le groupe de sujets normaux et le groupe de sujets hypertendus. L’analyse spectrale croisée de RR et de la pression artérielle systolique a permis d’évaluer dans l’hypertension artérielle (HTA), essentielle une sensibilité du baroréflexe atténuée, accompagnée d’une réactivité vagale réduite en présence d’une activité et d’une réactivité sympathique augmentées suggérant une altération sympathovagale dans l’HTA. Dans le groupe de sujets hypertendus traités (Trandolapril 2mg/jour), nous avons identifié un groupe de répondeurs au traitement par le Trandolapril et un groupe de non répondeurs à ce type de thérapie anti-hypertensive. Le groupe répondeur avait un profil hyper-adrénergique avec une hyper-réactivité sympathique, une fréquence cardiaque et des pressions artérielles diastolique et systolique plus élevées au repos. Dans le groupe total traité au Trandolapril, la densité des récepteurs ß2 adrénergiques a doublé, après thérapie, alors que la réactivité des basses fréquences obtenues à l’analyse spectrale a augmenté. Nous avons montré dans notre étude qu’un IECA a pu inhiber le mécanisme facilitateur de l’angII sur les terminaisons nerveuses sympathiques et a permis ainsi de réduire l’hyperactivité sympathique et le mécanisme de « down regulation » des récepteurs ß2 adrénergiques rendant ainsi l’expression de l’influence du SNA post synaptique plus efficace. Dans l’ensemble de nos protocoles cliniques, par l’utilisation de l’analyse spectrale des signaux RR, de la pression artérielle systolique,de la pression artérielle diastolique et de la respiration, nous avons montré que cette technique non invasive permet de décrire et de mieux comprendre les mécanismes physiologiques, physiopathologiques et pharmacologiques reliés au système nerveux autonome et à l’hypertension artérielle essentielle. / The spectral analysis of the heart rate, the systolic blood pressure, the diastolic blood pressure and the respiration with the Fast Fourier Transform, is considered as a non-invasive technique for the determination of the autonomic nervous system activity. In a population of normal volunteer subjects, we obtained in the basal state, low-frequency oscillations related to the sympathetic autonomous nervous system (0.05-0.15Hz) and the high-frequency oscillations (0.2Hz), which represent, on RR intervals, the respiratory sinus arrhythmia corresponding to vagal activity. We compared the sympathetic nervous system stimulation tests triggered by the transition from resting to voluntary orthostatic positions and the transition from resting to orthostatic position using tilt table at 60o. We also compared a normal blood pressure group to a hypertensive group which were both subject to the transition from resting to voluntary orthostation and for whom we evaluated the baroreflex sensitivity and the sympathetic response by measuring circulating catecholamines. In a group of subjects having an essential arterial hypertension, we have evaluated the effect of hypotensive therapy, by the Trandolapril which is an Angiotensin Converting Enzyme Inhibitor. In the hypertensive group, we evaluated the sympathetic stimulation using the voluntary orthostation, and we have also proceeded to a 3 minutes isometric exercise at 30% of maximum force. We have also completed our evaluation by measuring both the ß2 adrenergic receptor density on isolated lymphocytes and the contractility index using the echocardiography in M mode. In both sympathetic nervous system stimulation types by orthostatic position, the results have shown, for normal blood pressure volunteer subject groups, a significant increase in concentration of plasma catecholamines with an increase of heart rate (HR) and the low frequency RR, confirming therefore that we are in the presence of a sympathetic stimulation state. At the same time, we observed a significant decrease of high frequency of RR, suggesting a vagal withdrawal during the stimulation. We observed six cases of orthostatic hypotension from the tilt table test. We compared the voluntary orthostatic position between normal and hypertension subject groups. The results with combined spectral analysis of RR and the systolic blood pressure allowed to evaluate in the essential high blood pressure a reduced baroreflex sensitivity along with a reduced vagal reactivity in presence of increased sympathetic activity and reactivity suggesting a sympatho-vagal alteration in essential arterial hypertension. In hypertensive subjects treated with Trandolapril 2mg/day, we have identified a group responding to Trandolapril treatment and a group of non-responders to this type of anti-hypertensive therapy. The responding group has an hyper-adrenergic profile with higher sympathetic reactivity, heart rate and arterial diastolic and systolic pressures at rest. In the total group treated with Trandolapril, the ß2 adrenergic receptor density has doubled after therapy, while the reactivity of low frequencies obtained from spectral analysis has increased. We have shown in this study that Angiotensin Converting Enzyme Inhibitor could inhibit the facilitatory mechanism of angII on sympathetic nerve terminals and therefore allowed the reduction of the sympathetic hyperactivity and the cause of a beta2 adrenergic “down regulation”. Thus it allowed us to obtain an increased density of the receptors and the expression of more effective influence of post synaptic Sympathetic nervous system. In all of our clinical protocols, using spectral analysis of RR, systolic blood pressure, diastolic blood pressure and breathing signals, we have shown that this non-invasive technique has helped to describe and to better understand the physiological and pharmacological mechanisms related to the autonomic nervous system in normotensive and hypertensive subjects.