There is clear evidence that the autonomic nervous system (ANS) is lateralized at both the peripheral as well as the central levels of the nervous system. Both the vagus and the sympathetic ganglia asymmetrically innervate the sino-atrial node and the myocardium of the heart. This lateralization has also been observed in afferent as well as efferent projections to nuclei in the brainstem, hypothalamus, and amygdala. Where laterality has not been as clear is in regions of the frontal lobe dedicated to the regulation of autonomic nervous system responses. This study addressed that issue via the implementation of lateralized autonomic response-evoking tasks. With the use of cardiovascular and electrodermal measures, the present study indexed autonomic responses to lateralized stimuli. This study also explored the role of lateralization within sex as well as in relation to reported gender identity. The findings lend support to the right hemisphere as serving a dominant role in regulating sympathetic nervous system activity, while lending less conclusive support for lateralization of parasympathetic nervous system regulation. Men demonstrated greater lateralization for sympathetic nervous system responses across several different metrics of autonomic indices. The exploration of gender variables in relation to lateralization of autonomic responses was generally not supported. / Master of Science

Abstract Analysis of beat-to-beat heart rate variability (HRV) provides information of cardiac vagal outflow to the sinus node. Some methodological problems might, however, be involved in the analysis of cardiac vagal outflow from ambulatory Holter recordings, such as saturation, physical activity, and abrubt prolongations of R-R intervals unrelated to respiration. The purpose of this thesis was to assess the physiological basis of beat-to-beat HRV and to develop and assess new methods for the quantification of cardiac autonomic modulation from ambulatory Holter recordings. The study population consisted of 89 healthy volunteers (age 24 ± 4 years) and 590 patients with a recent acute myocardial infarction (AMI, age 61 ± 10 years). The relationship between R-R interval length and the high-frequency (HF) spectral power of the R-R intervals was assessed in 76 healthy subjects and 82 post-AMI patients. The effects of aerobic exercise training on the dynamics between R-R interval and HF power were evaluated by means of a controlled 8-week training intervention (n = 17). The effects of sympathetic activation and concomitant sympathetic and vagal outflow on beat-to-beat HR dynamics were studied in laboratory conditions (n = 13). A new method for quantifying beat-to-beat HRV from the R-R interval lengths where the relationship between HF power and R-R interval is most linear was developed to avoid the confounding effects of possible saturation, physical activity, and random R-R interval dynamics. The clinical significance of the new method was assessed in a series of 590 post-AMI patients. Saturated HF R-R interval dynamics, expressed as a lack of increase in HF power despite an increased R-R interval, was observed in 35 healthy subjects and 9 post-AMI patients. In the training study, 7 subjects out of a total of 17 had saturated HF power before the intervention. After the training period, 5 new cases of saturated HF power were observed. In laboratory conditions, co-activation of sympathetic and vagal outflow resulted in random R-R interval dynamics. In post-AMI patients, HF power analyzed exclusively from the R-R intervals where the relationship between the R-R interval and HF power was most linear (Vindex) predicted independently the occurrence of SCD among post-AMI patients, while traditionally analyzed HF power did not. In conclusion, the saturation of beat-to-beat HRV in ambulatory conditions is a common phenomenon. The prevalence of saturated HF power increases due to enhanced cardiac vagal outflow induced by aerobic training. Finally, the novel analysis of vagally mediated HRV (Vindex) provides unique information that cannot be obtained by traditional analysis of HF R-R interval dynamics.

O treinamento aeróbico é recomendado para a redução da pressão arterial (PA) de hipertensos. Existe uma forte associação entre a redução aguda da PA após uma sessão de exercício aeróbico e o efeito hipotensor crônico do treinamento, sendo que alguns estudos demonstraram que o efeito hipotensor agudo é maior quando o exercício é executado ao final do dia, sugerindo que o treinamento também tenha maior efeito se executado nessa fase do dia, o que ainda não foi investigado. Assim, o objetivo deste estudo foi avaliar e comparar, em hipertensos medicados, o efeito do treinamento aeróbico realizado pela manhã e ao final do dia sobre a PA e seus mecanismos hemodinâmicos e autonômicos, bem como sobre a qualidade do sono. Para tanto, 50 homens hipertensos medicados (30 a 65 anos) foram alocados, de maneira aleatória, em 3 grupos: treinamento pela manhã (MT, iniciado entre 7- 9h), treinamento ao final dia (FDT, iniciado entre 18-20h) e controle (GC - metade em cada horário). As intervenções foram realizadas 3 vezes por semana por 10 semanas. No MT e FDT, os indivíduos pedalaram em cicloergômetro (45min, intensidade entre limiares ventilatórios). No GC, eles fizeram 30 min de alongamento por sessão. No inicio e ao final do estudo, foram avaliados: PA ambulatorial; qualidade do sono; e a PA clínica e seus mecanismos hemodinâmicos e autonômicos medidos entre 7-9h e entre 18-20h. ANOVAs mistas de 2 fatores foram empregadas, considerando-se p<=0,05. A PA diastólica de 24h (p=0,04) e de sono (p=0,05) diminuíram apenas no FDT de forma diferente do MT e GC e qualidade de sono não se alterou significantemente em nenhum grupo. Nas avaliações realizadas entre 7-9h, a PA sistólica, a PA média e a resistência vascular periférica (RVP) diminuíram de forma diferente do GC apenas no FDT (-5±6 mmHg, -4±4 mmHg e -3±3U, p<0,05). A frequência cardíaca (FC) diminuiu e o balanço simpatovagal diferiu do GC de forma similar no MT e FDT, enquanto a sensibilidade barorreflexa cardíaca (SBRc) aumentou nos dois grupos de treinamento, porém mais no FDT (+0,4±0,4 vs. +0,3±0,6 ms/mmHg, p=0,002). A modulação vasomotora simpática (VTPAS) não aumentou no MT e diminuiu no FDT, ambos diferentes do GC (p=0,001). Nas avaliações realizadas entre 18-20h, a PA sistólica (p<0,001), a PA média (p<0,001) e a RVP (p=0,03) reduziram significantemente e de forma diferente do GC apenas no FDT. Portanto, em hipertensos medicados, o treinamento aeróbico realizado ao final do dia promove redução da PA clínica e ambulatorial. Essa queda ocorre devido à diminuição da RVP, provavelmente decorrente da redução da modulação simpática vasomotora, o que se acompanha de redução da FC, possivelmente associada à melhora da modulação autonômica cardiovascular. O treinamento realizado pela manhã reduz a FC e melhora a modulação autonômica cardiovascular. Dessa forma, em homens hipertensos medicados, o treinamento aeróbico realizado ao final do dia é mais eficaz em reduzir a PA e o risco cardiovascular, sendo o mais indicado nessa população / Aerobic training is recommended to decrease blood pressure (BP) in hypertension. There is a strong correlation between the hypotensive post-effect of a single aerobic exercise session and the chronic hypotensive effect produced by aerobic training, and some studies have demonstrated that this acute hypotensive effect is greater when exercise is executed in the evening, which suggests that training effect might also be greater when performed at this time of day. Thus, the aim of this study was to assess and compare, in treated hypertensive men, the effect of aerobic training performed in the morning and in the evening on BP and its hemodynamic and autonomic mechanisms, as well as on sleep quality. For this, 50 treated hypertensive men (30 to 65 years old) were randomly allocated into 3 groups: morning training (MT, starting between 7-9 a.m.), evening training (ET, starting between 6-8 p.m.) and control group (CG, half at each time of day). The interventions were performed 3times/week for 10 weeks. MT and ET was composed by cycling on an ergometer (45 min, intensity between the ventilatory thresholds). CG performed stretching for 30 min. At the beginning and end of the study, the following variables were assessed: ambulatory BP; sleep quality, and clinic BP and its hemodynamics and autonomic mechanisms measured between 7-9a.m. and between 6-8 p.m. Two-way mixed ANOVAs were employed, considering p<=0.05. Twentyfour hour (p=0.04) and asleep (p=0.05) diastolic BPs decreased only in the ET; which was different from MT and CG, while sleep quality did not change in any group. For assessments made between 7-9 a.m., systolic BP, mean BP and systemic vascular resistance (SVR) decreased only in FDT, which was different from CG (-5±6 mmHg, -4±4 mmHg e -3±3U, p<0.05). Heart rate (HR) decreased and sympathovagal balance was different from CG in the MT and ET, while cardiac baroreflex sensibility (cBRS) increased in both training groups, but the increase was greater in the ET (+0.4±0.4 vs. +0.3±0.6 ms/mmHg, p=0,002). Sympathetic vasomotor modulation (TVSBP) did not change in MT and decreased in the ET, with both responses different from CG (p=0.001). For assessments made between 6-8 p.m., systolic BP (p<0.001), mean BP (p<0.001) and SVR (p=0.03) decreased significantly only in FDT and these responses were different from the MT and CG. Therefore, in treated hypertensive men, aerobic training performed in the evening decreases clinic and ambulatory BP. These reduction occurs due to a decrease in SVR, possibly due to the decrease in sympathetic vasomotor modulation; and it is followed by a decrease in HR, possibly associated to an improvement of cardiovascular autonomic modulation. Aerobic training performed in the morning decreases HR and improves cardiovascular autonomic modulation. Thus, in treated hypertensive men, aerobic training performed in the evening is more effective to decrease BP and cardiovascular risk, being more indicated to these patients

O treinamento aeróbico é recomendado para a redução da pressão arterial (PA) de hipertensos. Existe uma forte associação entre a redução aguda da PA após uma sessão de exercício aeróbico e o efeito hipotensor crônico do treinamento, sendo que alguns estudos demonstraram que o efeito hipotensor agudo é maior quando o exercício é executado ao final do dia, sugerindo que o treinamento também tenha maior efeito se executado nessa fase do dia, o que ainda não foi investigado. Assim, o objetivo deste estudo foi avaliar e comparar, em hipertensos medicados, o efeito do treinamento aeróbico realizado pela manhã e ao final do dia sobre a PA e seus mecanismos hemodinâmicos e autonômicos, bem como sobre a qualidade do sono. Para tanto, 50 homens hipertensos medicados (30 a 65 anos) foram alocados, de maneira aleatória, em 3 grupos: treinamento pela manhã (MT, iniciado entre 7- 9h), treinamento ao final dia (FDT, iniciado entre 18-20h) e controle (GC - metade em cada horário). As intervenções foram realizadas 3 vezes por semana por 10 semanas. No MT e FDT, os indivíduos pedalaram em cicloergômetro (45min, intensidade entre limiares ventilatórios). No GC, eles fizeram 30 min de alongamento por sessão. No inicio e ao final do estudo, foram avaliados: PA ambulatorial; qualidade do sono; e a PA clínica e seus mecanismos hemodinâmicos e autonômicos medidos entre 7-9h e entre 18-20h. ANOVAs mistas de 2 fatores foram empregadas, considerando-se p<=0,05. A PA diastólica de 24h (p=0,04) e de sono (p=0,05) diminuíram apenas no FDT de forma diferente do MT e GC e qualidade de sono não se alterou significantemente em nenhum grupo. Nas avaliações realizadas entre 7-9h, a PA sistólica, a PA média e a resistência vascular periférica (RVP) diminuíram de forma diferente do GC apenas no FDT (-5±6 mmHg, -4±4 mmHg e -3±3U, p<0,05). A frequência cardíaca (FC) diminuiu e o balanço simpatovagal diferiu do GC de forma similar no MT e FDT, enquanto a sensibilidade barorreflexa cardíaca (SBRc) aumentou nos dois grupos de treinamento, porém mais no FDT (+0,4±0,4 vs. +0,3±0,6 ms/mmHg, p=0,002). A modulação vasomotora simpática (VTPAS) não aumentou no MT e diminuiu no FDT, ambos diferentes do GC (p=0,001). Nas avaliações realizadas entre 18-20h, a PA sistólica (p<0,001), a PA média (p<0,001) e a RVP (p=0,03) reduziram significantemente e de forma diferente do GC apenas no FDT. Portanto, em hipertensos medicados, o treinamento aeróbico realizado ao final do dia promove redução da PA clínica e ambulatorial. Essa queda ocorre devido à diminuição da RVP, provavelmente decorrente da redução da modulação simpática vasomotora, o que se acompanha de redução da FC, possivelmente associada à melhora da modulação autonômica cardiovascular. O treinamento realizado pela manhã reduz a FC e melhora a modulação autonômica cardiovascular. Dessa forma, em homens hipertensos medicados, o treinamento aeróbico realizado ao final do dia é mais eficaz em reduzir a PA e o risco cardiovascular, sendo o mais indicado nessa população / Aerobic training is recommended to decrease blood pressure (BP) in hypertension. There is a strong correlation between the hypotensive post-effect of a single aerobic exercise session and the chronic hypotensive effect produced by aerobic training, and some studies have demonstrated that this acute hypotensive effect is greater when exercise is executed in the evening, which suggests that training effect might also be greater when performed at this time of day. Thus, the aim of this study was to assess and compare, in treated hypertensive men, the effect of aerobic training performed in the morning and in the evening on BP and its hemodynamic and autonomic mechanisms, as well as on sleep quality. For this, 50 treated hypertensive men (30 to 65 years old) were randomly allocated into 3 groups: morning training (MT, starting between 7-9 a.m.), evening training (ET, starting between 6-8 p.m.) and control group (CG, half at each time of day). The interventions were performed 3times/week for 10 weeks. MT and ET was composed by cycling on an ergometer (45 min, intensity between the ventilatory thresholds). CG performed stretching for 30 min. At the beginning and end of the study, the following variables were assessed: ambulatory BP; sleep quality, and clinic BP and its hemodynamics and autonomic mechanisms measured between 7-9a.m. and between 6-8 p.m. Two-way mixed ANOVAs were employed, considering p<=0.05. Twentyfour hour (p=0.04) and asleep (p=0.05) diastolic BPs decreased only in the ET; which was different from MT and CG, while sleep quality did not change in any group. For assessments made between 7-9 a.m., systolic BP, mean BP and systemic vascular resistance (SVR) decreased only in FDT, which was different from CG (-5±6 mmHg, -4±4 mmHg e -3±3U, p<0.05). Heart rate (HR) decreased and sympathovagal balance was different from CG in the MT and ET, while cardiac baroreflex sensibility (cBRS) increased in both training groups, but the increase was greater in the ET (+0.4±0.4 vs. +0.3±0.6 ms/mmHg, p=0,002). Sympathetic vasomotor modulation (TVSBP) did not change in MT and decreased in the ET, with both responses different from CG (p=0.001). For assessments made between 6-8 p.m., systolic BP (p<0.001), mean BP (p<0.001) and SVR (p=0.03) decreased significantly only in FDT and these responses were different from the MT and CG. Therefore, in treated hypertensive men, aerobic training performed in the evening decreases clinic and ambulatory BP. These reduction occurs due to a decrease in SVR, possibly due to the decrease in sympathetic vasomotor modulation; and it is followed by a decrease in HR, possibly associated to an improvement of cardiovascular autonomic modulation. Aerobic training performed in the morning decreases HR and improves cardiovascular autonomic modulation. Thus, in treated hypertensive men, aerobic training performed in the evening is more effective to decrease BP and cardiovascular risk, being more indicated to these patients

Abstract Regular aerobic training has been suggested to protect the heart by increasing cardiac vagal activity. The aims of this study were to evaluate the autonomic regulation of heart rate (HR) during and after exercise, during aerobic training interventions and to study the association between autonomic regulation and the training response in healthy male subjects. HR variability assessment was used to study the effects of exercise on autonomic regulation of HR. The whole study population consisted of 70 volunteer male subjects (age 36 ± 10 years). The recovery of the autonomic nervous system after prolonged exhaustive exercise was studied in a group of 10 subjects. The training interventions included 51 subjects. The effects of training volume on autonomic regulation were assessed (n = 46) during a controlled eight-week training intervention. The association between training and autonomic regulation was studied (n = 24) during a ten-month period of home-based training based on the American College of Sports Medicine recommendations. Finally, the association between autonomic regulation and the individual training response was analysed (n = 51) after eight weeks of controlled training. The recovery rate of vagally mediated high-frequency (HF) power of HR variability after prolonged exhaustive exercise was associated with physical fitness (r = -0.71, P &lt; 0.016). Moderate (3 hours/week) and high-volume (6 hours/week) aerobic training results in a similar increase in HR variability indices. HF power increased from 6.19 ± 1.02 to 6.76 ± 0.96 ln ms2 (P &lt; 0.001) and from 6.61 ± 1.01 to 7.12 ± 0.92 ln ms2 (P &lt; 0.001) after moderate and high-volume training, respectively. During the home-based training program, the changes in HF power were associated with the changes in the fitness (r = 0.44, P &lt; 0.05), body mass index (r = -0.44, P &lt; 0.05) and the amount of training (r = 0.41, p &lt; 0.05). Finally, a significant correlation was observed between the training response and the baseline HF power (r = 0.52, P = 0.001). HF power accounted for 27 % of the change as an independent predictor of the aerobic training response. In conclusion, a highly controlled aerobic training intervention of eight weeks, including six 30-min sessions a week at an intensity of 70–80 % of maximum HR, is a sufficient intervention to increase cardiac vagal outflow and the offered home-based training according the current guidelines maintains the high cardiac vagal outflow. Secondly, high vagal activity at baseline is associated with the improvement in aerobic fitness caused by aerobic training, suggesting that the cardiovascular autonomic function is an important determinant of the response to aerobic training.

Abstract This thesis describes the laser Doppler technique based on a self-mixing effect in a diode laser to noninvasive cardiovascular pulse detection in a human wrist above the radial artery. The main applications of self-mixing interferometry described in this thesis in addition to pulse detection are arterial pulse shape and autonomic regulation measurements. The elastic properties of the arterial wall are evaluated and compared to pulse wave velocity variation at different pressure conditions inside the radial artery. The main advantages of self-mixing interferometry compared to conventional interferometers are that the measurement set up is simple, because basically only one optical component, the laser diode, is needed. The use of fewer components decreases the price of the device, thus making it inexpensive to use. Moreover, an interferometer can be implemented in a small size and it is easy to control because only one optical axis has to be adjusted. In addition, an accuracy, which corresponds to half of the wavelength of the light source, can be achieved. These benefits make this technique interesting for application to the measurement of different parameters of the cardiovascular pulse. In this thesis, measurement of three different parameters from cardiovascular pulsation in the wrist is studied. The first study considers arterial pulse shape measurement. It was found that an arterial pulse shape reconstructed from the Doppler signal correlates well to the pulse shape of a blood pressure pulse measured with a commercial photoplethysmograph. The second study considers measurement of autonomic regulation using the Doppler technique. It was found that the baroreflex part of autonomic regulation can be measured from the displacement of the arterial wall, which is affected by blood pressure variation inside the artery. In the third study, self-mixing interferometry is superimposed to evaluate the elastic properties of the arterial wall. It was found that the elastic modulus of the arterial wall increases as blood pressure increases. Correlations between measurements and theoretical values were found but deviation in measured values was large. It was noticed that the elastic modulus of the arterial wall and pulse wave velocity behave similarly as a function of blood pressure. When the arterial pressure increases, both the elastic modulus and pulse wave velocity reach higher values than in lower pressure.

A hipotensão pós-exercício (HPE) se caracteriza pela redução da pressão arterial (PA) após uma sessão de exercício. Diversos estudos têm investigado a HPE e seus mecanismos utilizando as seguintes formas de cálculo: I = PA pós-exercício - PA pré-exercício; II = PA pós-exercício - PA pós-controle; e III = [(PA pós-exercício - PA pré-exercício) - (PA pós-controle - PA pré-controle)]. Embora esses estudos tenham demonstrado a ocorrência da HPE em diferentes populações e sua relevância clínica, pouco se sabe sobre sua reprodutibilidade. Dessa forma, este estudo objetivou verificar a reprodutibilidade (erro sistemático, confiabilidade e concordância) da HPE e de seus mecanismos hemodinâmicos e autonômicos avaliados pelas 3 formas de cálculo expostas. Para tanto, 30 indivíduos realizaram 4 sessões experimentais divididas em 2 blocos (teste e reteste). Cada bloco foi composto por uma sessão de exercício (cicloergômetro, 45min, 50% do VO2pico) e uma controle (repouso sentado), realizadas em ordem aleatória. Antes e após as intervenções, foram medidos: a PA (auscultatória e fotopletismográfica), o débito cardíaco (reinalação de CO2), a frequência cardíaca (FC - eletrocardiograma) e a modulação autonômica cardiovascular (análise espectral das variabilidades da FC e da PA, além da sensibilidade barorreflexa). A presença de erro sistemático foi avaliada pelo test-t pareado, a confiabilidade pelo coeficiente de correlação intraclasse (CCI) e a concordância pelo erro típico (ET). A HPE e seus mecanismos hemodinâmicos e autonômicos avaliados pelas 3 formas de cálculo não apresentaram erro sistemático. A HPE sistólica apresentou confiabilidade alta e a diastólica confiabilidade baixa a moderada, com melhor confiabilidade na forma de cálculo II. Em geral, os mecanismos hemodinâmicos e autonômicos apresentaram confiabilidade moderada a baixa, com maior confiabilidade com a forma de cálculo I. Para finalizar, os parâmetros de concordância variaram entre as 3 formas de cálculo, o que implica que o ET específico de cada variável para cada forma de cálculo deve ser considerado para a estimativa do tamanho amostral necessário em estudos e para o cálculo da mínima diferença detectável na prática clínica quando o objetivo for comparar as respostas pós-exercício obtidas em diferentes condições / Post-exercise hypotension is characterized by a reduction in blood pressure (BP) after a single session of exercise. Several studies have investigated PEH and its mechanisms and they have employed the following methods of calculation: I = post-exercise BP - pre-exercise BP; II = post-exercise BP - post-control BP; and III = [(post-exercise BP - pre-exercise BP) - (post-control BP - pre-control BP)]. Although these studies have demonstrated the occurrence of PEH in different populations and its clinical relevance, little is known about the reproducibility of PEH. Thus, the current study was designed to determine the reproducibility (systematic error, reliability and agreement) of PEH and its hemodynamic and autonomic mechanisms evaluated by the three methods of calculation exposed. For this purpose, 30 subjects performed 4 experimental sessions divided into two blocks (test and retest). Each block was composed by one exercise (cycle ergometer, 45 min, 50% of VO2peak) and one control (seated rest) session executed in a random order. Before and after the interventions, the following parameters were measured: BP (auscultatory and photoplethysmographic), cardiac output (CO2 rebreathing), heart rate (HR - electrocardiogram) and cardiovascular autonomic modulation (spectral analysis of HR and BP variabilities, as well as spontaneous baroreflex sensitivity). The presence of systematic bias was evaluated by paired t-test, reliability by intraclass correlation coefficient (ICC) and agreement by typical error (TE). PEH and its hemodynamic and autonomic mechanisms evaluated by the three methods of calculation did not present systematic bias. Systolic PEH presented high reliability and diastolic PEH showed low to moderate reliability, with better results for the method II. In general, the hemodynamic and autonomic mechanisms presented low to moderate reliabilities, with better results for the method I. Lastly, agreement parameters varied among the three methods of calculation, which implies that the specific value of TE for each variable and each method of calculation should be used for estimating the sample size required in studies and establishing the minimal detectable change in clinical settings when the goal is to compare post-exercise responses obtained in different conditions

The transcranial direct current stimulation (tDCS) is a neuromodulatory technique able to modify cortical excitability and presumably modulate the neural activity of cortical areas involved in autonomic regulation, such as the medial prefrontal cortex (MFPC) and insular cortex (IC). Regarding the ANS, there is evidence of hyper-sympathetic activation in people with HTN. To contribute to the discussion, this thesis was divided as follows: The first chapter titled "Heart rate variability (HRV): analytical methods and their applicability " consists of a review article, aiming at the theoretical foundation about methods of assessment of HRV and its prospects for use. The second chapter consists of an original paper entitled "Effect of transcranial direct current stimulation on heart rate variability in hypertensive women". This research applied anodal tDCS, cathodic and simulated (sham) separately on the left temporal lobe (T3) of hypertensive women showed significant increases in parasympathetic activity, only with the application of cathodic tDCS. However, one cannot say which specific area of the brain was responsible for variations in HRV, since the two electrodes were about regions involved in autonomic control and still not know what the real impact of bipolar stimulation on brain physiology. Although there are limitations, our results may assist in developing a new tool to explore noninvasively the autonomic nervous system, and even open new therapeutic perspectives for treatment of their disorders such as hypertension. / Fundação de Amparo a Pesquisa do Estado de Alagoas / A estimulação transcraniana por corrente contínua (ETCC) é uma técnica neuromodulatória capaz de modificar a excitabilidade cortical e supostamente modular a atividade neural de áreas corticais envolvidas na regulação autonômica, como o córtex pré-frontal medial (CPFM) e o córtex insular (CI). Com relação ao SNA, existem evidências de hiper-ativação simpática em pessoas com HAS. Para colaborar com a discussão, esta dissertação foi dividida da seguinte forma: o primeiro capítulo intitulado de Variabilidade da frequência cardíaca (VFC): métodos de análise e sua aplicabilidade , sendo constituído por um artigo de revisão, objetivando a fundamentação teórica a respeito dos métodos de avaliação da VFC e suas perspectivas de utilização. O segundo capítulo é composto por um artigo original intitulado: Efeitos da estimulação transcraniana por corrente contínua sobre a variabilidade da frequência cardíaca de mulheres hipertensas . Neste estudo foi aplicada a ETCC anódica, catódica e simulada (sham), separadamente, sobre o lobo temporal esquerdo (T3) de mulheres hipertensas e evidenciou aumentos significativos na atividade parassimpática, somente com a aplicação da ETCC catódica. Todavia, não se pode afirmar qual área específica do cérebro foi responsável pelas variações na VFC, pois, os dois eletrodos estavam sobre regiões envolvidas no controle autonômico e ainda não sabemos qual o real impacto da estimulação bipolar no cérebro sobre parâmetros fisiológicos. Embora haja limitações, nossos resultados podem auxiliar no desenvolvimento de uma nova ferramenta para explorar de forma não invasiva o sistema nervoso autônomo, e até mesmo abrir novas perspectivas terapêuticas para tratamento de seus distúrbios como é o caso da hipertensão.

A hipotensão pós-exercício (HPE) se caracteriza pela redução da pressão arterial (PA) após uma sessão de exercício. Diversos estudos têm investigado a HPE e seus mecanismos utilizando as seguintes formas de cálculo: I = PA pós-exercício - PA pré-exercício; II = PA pós-exercício - PA pós-controle; e III = [(PA pós-exercício - PA pré-exercício) - (PA pós-controle - PA pré-controle)]. Embora esses estudos tenham demonstrado a ocorrência da HPE em diferentes populações e sua relevância clínica, pouco se sabe sobre sua reprodutibilidade. Dessa forma, este estudo objetivou verificar a reprodutibilidade (erro sistemático, confiabilidade e concordância) da HPE e de seus mecanismos hemodinâmicos e autonômicos avaliados pelas 3 formas de cálculo expostas. Para tanto, 30 indivíduos realizaram 4 sessões experimentais divididas em 2 blocos (teste e reteste). Cada bloco foi composto por uma sessão de exercício (cicloergômetro, 45min, 50% do VO2pico) e uma controle (repouso sentado), realizadas em ordem aleatória. Antes e após as intervenções, foram medidos: a PA (auscultatória e fotopletismográfica), o débito cardíaco (reinalação de CO2), a frequência cardíaca (FC - eletrocardiograma) e a modulação autonômica cardiovascular (análise espectral das variabilidades da FC e da PA, além da sensibilidade barorreflexa). A presença de erro sistemático foi avaliada pelo test-t pareado, a confiabilidade pelo coeficiente de correlação intraclasse (CCI) e a concordância pelo erro típico (ET). A HPE e seus mecanismos hemodinâmicos e autonômicos avaliados pelas 3 formas de cálculo não apresentaram erro sistemático. A HPE sistólica apresentou confiabilidade alta e a diastólica confiabilidade baixa a moderada, com melhor confiabilidade na forma de cálculo II. Em geral, os mecanismos hemodinâmicos e autonômicos apresentaram confiabilidade moderada a baixa, com maior confiabilidade com a forma de cálculo I. Para finalizar, os parâmetros de concordância variaram entre as 3 formas de cálculo, o que implica que o ET específico de cada variável para cada forma de cálculo deve ser considerado para a estimativa do tamanho amostral necessário em estudos e para o cálculo da mínima diferença detectável na prática clínica quando o objetivo for comparar as respostas pós-exercício obtidas em diferentes condições / Post-exercise hypotension is characterized by a reduction in blood pressure (BP) after a single session of exercise. Several studies have investigated PEH and its mechanisms and they have employed the following methods of calculation: I = post-exercise BP - pre-exercise BP; II = post-exercise BP - post-control BP; and III = [(post-exercise BP - pre-exercise BP) - (post-control BP - pre-control BP)]. Although these studies have demonstrated the occurrence of PEH in different populations and its clinical relevance, little is known about the reproducibility of PEH. Thus, the current study was designed to determine the reproducibility (systematic error, reliability and agreement) of PEH and its hemodynamic and autonomic mechanisms evaluated by the three methods of calculation exposed. For this purpose, 30 subjects performed 4 experimental sessions divided into two blocks (test and retest). Each block was composed by one exercise (cycle ergometer, 45 min, 50% of VO2peak) and one control (seated rest) session executed in a random order. Before and after the interventions, the following parameters were measured: BP (auscultatory and photoplethysmographic), cardiac output (CO2 rebreathing), heart rate (HR - electrocardiogram) and cardiovascular autonomic modulation (spectral analysis of HR and BP variabilities, as well as spontaneous baroreflex sensitivity). The presence of systematic bias was evaluated by paired t-test, reliability by intraclass correlation coefficient (ICC) and agreement by typical error (TE). PEH and its hemodynamic and autonomic mechanisms evaluated by the three methods of calculation did not present systematic bias. Systolic PEH presented high reliability and diastolic PEH showed low to moderate reliability, with better results for the method II. In general, the hemodynamic and autonomic mechanisms presented low to moderate reliabilities, with better results for the method I. Lastly, agreement parameters varied among the three methods of calculation, which implies that the specific value of TE for each variable and each method of calculation should be used for estimating the sample size required in studies and establishing the minimal detectable change in clinical settings when the goal is to compare post-exercise responses obtained in different conditions

Abstract The quantitation of the variability in cardiovascular signals provides information about the autonomic neural regulation of the heart and the circulatory system. Several factors have an indirect effect on these signals as well as artifacts and several types of noise are contained in the recorded signal. The dynamics of RR and QT interval time series have also been analyzed in order to predict a risk of adverse cardiac events and to diagnose them. An ambulatory measurement setting is an important and demanding condition for the recording and analysis of these signals. Sophisticated and robust signal analysis schemes are thus increasingly needed. In this thesis, essential points related to ambulatory data acquisition and analysis of cardiovascular signals are discussed including the accuracy and reproducibility of the variability measurement. The origin of artifacts in RR interval time series is discussed, and consequently their effects and possible correction procedures are concidered. The time series including intervals differing from a normal sinus rhythm which sometimes carry important information, but may not be as such suitable for an analysis performed by all approaches. A significant variation in the results in either intra- or intersubject analysis is unavoidable and should be kept in mind when interpreting the results. In addition to heart rate variability (HRV) measurement using RR intervals, the dy- namics of ventricular repolarization duration (VRD) is considered using the invasively obtained action potential duration (APD) and different estimates for a QT interval taken from a surface electrocardiogram (ECG). Estimating the low quantity of the VRD vari- ability involves obviously potential errors and more strict requirements. In this study, the accuracy of VRD measurement was improved by a better time resolution obtained through interpolating the ECG. Furthermore, RTmax interval was chosen as the best QT interval estimate using simulated noise tests. A computer program was developed for the time interval measurement from ambulatory ECGs. This thesis reviews the most commonly used analysis methods for cardiovascular vari- ability signals including time and frequency domain approaches. The estimation of the power spectrum is presented on the approach using an autoregressive model (AR) of time series, and a method for estimating the powers and the spectra of components is also presented. Time-frequency and time-variant spectral analysis schemes with applica- tions to HRV analysis are presented. As a novel approach, wavelet and wavelet packet transforms and the theory of signal denoising with several principles for the threshold selection is examined. The wavelet packet based noise removal approach made use of an optimized signal decomposition scheme called best tree structure. Wavelet and wavelet packet transforms are further used to test their effciency in removing simulated noise from the ECG. The power spectrum analysis is examined by means of wavelet transforms, which are then applied to estimate the nonstationary RR interval variability. Chaotic modelling is discussed with important questions related to HRV analysis.ciency in removing simulated noise from the ECG. The power spectrum analysis is examined by means of wavelet transforms, which are then applied to estimate the nonstationary RR interval variability. Chaotic modelling is discussed with important questions related to HRV analysis.