Submitted by Daniely Januário (daniely.januario@gmail.com) on 2018-02-27T12:09:08Z No. of bitstreams: 1 andrecalilesilva.pdf: 1255223 bytes, checksum: a4c2cc23c41ea20154aecc918238dd7d (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2018-03-01T15:08:13Z (GMT) No. of bitstreams: 1 andrecalilesilva.pdf: 1255223 bytes, checksum: a4c2cc23c41ea20154aecc918238dd7d (MD5) / Made available in DSpace on 2018-03-01T15:08:13Z (GMT). No. of bitstreams: 1 andrecalilesilva.pdf: 1255223 bytes, checksum: a4c2cc23c41ea20154aecc918238dd7d (MD5) Previous issue date: 2016-07-29 / PROQUALI (UFJF) / Introdução: A obesidade atinge crianças cada vez mais novas, podendo associar-se ao aumento da pressão arterial (PA). A sensibilidade barorreflexa (SBR) é o principal mecanismo de controle da PA a curto prazo e pode estar diminuída em crianças obesas. Objetivos: Comparar a SBR espontânea e variáveis hemodinâmicas (VH) de crianças normotensas, obesas e eutróficas. Materiais e métodos: A amostra de crianças com idade entre 6 e 9 anos foi dividida em dois grupos: obesos (IMC-z > 2; n=16) e eutróficos (IMC-z ≥ - 2 e ≤ 1; n=15). Um registro de 5 minutos da PA batimento a batimento (Finometer) e do eletrocardiograma (Biopac) foram utilizados para cálculo da SBR (método sequencial) e das VH. Todas as medidas foram registradas espontaneamente após 10 minutos de repouso na posição supina. Resultados: A SBR (p=0,28) e o índice de efetividade do barorreflexo (p=0,44) não foram significativamente diferentes entre os grupos. O grupo obeso apresentou valores significativamente maiores do que o grupo eutrófico para a pressão arterial sistólica (105,38±5,96 e 95,33±5,62; p<0,05), pressão arterial diastólica (65,56±7,26 e 57,33±5,62; p<0,05) e débito cardíaco (1,54±0,26 e 1,34±0,21; p<0,05). A frequência cardíaca, embora não tenha atingido a significância, também foi maior no grupo obeso (p=0,14). Correlações negativas foram encontradas entre a pressão arterial sistólica e a SBR (r=-0,52, p=0,03) no grupo obeso e entre FC e SBR no grupo obeso (r=-0,67, p=0,004) e eutrófico (r=-0,62, r=0,013). Considerações finais: A SBR não se encontra alterada devido a influência da obesidade no grupo estudado, porém, valores elevados da PA, DC e FC sugerem alteração da função simpática no grupo obeso. Parece que os danos na PA, ocasionados pela obesidade, precedem a debilidade do barorreflexo. / Introduction: Obesity affects increasingly younger children and may be associated with increased blood pressure (BP). Baroreflex sensitivity (BRS) is the main short-term BP control mechanism and may be decreased in obese children. Objectives: To compare spontaneous BRS and hemodynamic variables (HV) of normotensive, obese and eutrophic children. Materials and methodology: The sample of children aged between 6 and 9 years old were divided into two groups: obese (BMI-z> 2, n = 16) and normal weight (BMI-z ≥ - 2 and ≤ 1; n = 15). A 5 minute BP beat to beat record (Finometer) and electrocardiogram (Biopac) were used to calculate the BRS (sequential method) and HV. All measurements were recorded spontaneously after 10 minutes of rest in the supine position. Results: The BRS (p = 0,28) and the baroreflex effectiveness index (p = 0,44) were not significantly different between the groups. The obese group was significantly higher than the normal weight group for systolic blood pressure (105,38 ± 5,96 and 95,33 ± 5,62, p <0.05), diastolic blood pressure (65,56 ± 7,26 and 57,33 ± 5,62; p <0,05) and cardiac output (1,54 ± 0,26 and 1,34 ± 0,21; p <0,05). The heart rate, although not reaching a significant difference, was also higher in the obese group (p = 0,14). Negative correlations were found between systolic blood pressure and BRS (r = -0,52, p = 0,03) in the obese group and between HR and BRS in the obese group (r = - 0,67, p = 0,004) and eutrophic (r = -0,62, r = 0,013). Conclusion: The BRS was not altered by the influence of obesity in the study group. However, high BP, cardiac output and HR values suggest change in the sympathetic function in the obese group. It seems that the damage to the BP, caused by obesity, precede the baroreflex impairment.

A proposição deste trabalho foi avaliar a resposta do efeito vasomotor simpático, por meio da termografia infravermelha, em pacientes com disfunção temporomandibular (DTM) submetidos à acupuntura. Foram selecionados 17 pacientes com diagnóstico de DTM muscular e articular. Todos receberam tratamento de acupuntura com aplicação dos seguintes pontos: E6, E44, ID18, TA17, TA23, EX HN3, VB2, VB34, IG4 e F3. Foram realizados exames de termografia antes e depois da acupuntura na primeira e quinta sessões, tendo como áreas de interesse a região facial nas vistas frontal, laterais direita e esquerda. Também foram realizadas medições do nível de dor através da escala visual analógica (EVA) e medida de abertura bucal (AB) antes e depois das sessões. Foi observada uma diminuição da temperatura a curto prazo entre os momentos antes e depois da primeira sessão para a maioria das regiões de interesse analisadas (p<0,05). Porém, a longo prazo, a temperatura em quase todas as regiões analisadas se igualou para os momentos antes da primeira e quinta sessões. O tratamento da DTM com acupuntura resultou numa diminuição da sintomatologia dolorosa e leve melhora na abertura bucal. A termografia infravermelha mostrou-se um método efetivo no monitoramento da reatividade vascular no tratamento para DTM pela acupuntura. / The purpose of this study was to evaluate the response of the sympathetic vasomotor effect, through infrared thermography, in patients with temporomandibular dysfunction (TMD) submitted to acupuncture. Seventeen patients with a diagnosis of muscular and joint TMD were selected. All received acupuncture treatment with application of the following points: ST6, ST44, SI18, SJ17, SJ23, EX HN3, GB2, GB34, LI4, LR3. Thermography exams were performed before and after acupuncture in the first and fifth sessions, with areas of interest in the frontal region, right and left sides. Pain level measurements were also performed through visual analogue scale (EVA) and mouth opening measurement (AB) before and after the sessions. A short-term temperature decrease between the time before and after the first session was observed for most of the regions of interest analyzed (p <0.05). However, in the long run, the temperature in all regions analyzed equaled the moments before the first and fifth sessions. There was an improvement of the painful symptomatology and slight increase of the oral opening with acupuncture treatment for TMD. Infrared thermography showed to be an effective method for monitoring vascular reactivity in the treatment of TMD by acupuncture.

INTRODUÇÃO: Síncope inexplicada é considerada um fator de risco de morte súbita na cardiomiopatia hipertrófica (CMH). Em sua patogênese estão envolvidos meca-nismos diversos, incluindo a dificuldade de adaptação da resistência vascular sistêmica ao exercício e ao estresse ortostático, que pode ser influenciada por uma disfunção do sistema nervoso autônomo. Os objetivos deste estudo foram comparar a função nervosa autonômica em portadores de CMH com e sem síncope, bem como avaliar o valor diagnóstico do teste de inclinação (TI) na investigação de síncope nessa população. MÉTODOS: Foram incluídos 37 pacientes, 16 com síncope inexplicada à avaliação rotineira e 21 sem síncope. A função nervosa autonômica foi medida pela sensibilidade do barorreflexo (BR) espontâneo e do induzido por fenilefrina e pela variabilidade da freqüência cardíaca (VFC). As variáveis da VFC consideradas no domínio do tempo foram: desvio-padrão de todos os intervalos RR normais (SDNN); raiz quadrada da média do quadrado das diferenças entre intervalos RR normais adjacentes (RMSSD); e percentagem de intervalos RR adjacentes com diferença superior a 50 ms (pNN50), durante o eletrocardiograma de 24 horas. No domínio da freqüência, foram considerados os componentes de alta, baixa e muito baixa freqüência e a densidade total do espectro, tanto em valores absolutos como em unidades normalizadas, em repouso e aos 60 graus de inclinação. As medidas da pressão arterial sistólica e diastólica, batimento a batimento, e as medidas do índice sistólico, do índice cardíaco e da resistência vascular sistêmica, obtidas pela cardiografia por impedância, foram comparadas, entre os grupos, a 0, 30 e 60 graus de inclinação. O TI consistiu na exposição dos pacientes a 60º de inclinação por 40 minutos, ou até uma resposta positiva. RESULTADOS: A sensibilidade do BR, tanto espontâneo (16,46±12,99 vs 18,31±9,88 ms/mmHg, p=0,464) como induzido por fenilefrina (18,33±9,31 vs 15,83±15,48 ms/mmHg, p=0,521) foi semelhante nos grupos síncope e sem síncope. Não foram observadas diferenças nos valores de SDNN (137,69±36,62 vs 145,95±38,07 ms, p=0,389). O grupo síncope apresentou menores valores de RMSSD (24,88±10,03 vs 35,58±16,43 ms, p=0,042) e tendência a menor pNN50 (4,51±3,78 vs 8,83±7,98 %, p=0,085) e a menores valores do componente de alta freqüência da análise espectral, em repouso (637,59±1295,53 vs 782,65±1264,14 ms2, p=0,075). Não foram observadas diferenças significativas entre os grupos nos demais parâmetros analisados no domínio da freqüência. A adaptação das variáveis hemodinâmicas aos diferentes graus de inclinação foi semelhante entre os grupos nas várias posições estudadas. A positividade ao TI foi semelhante nos dois grupos (6% no grupo síncope e 33% no sem síncope, p=0,053). A sensibilidade, a especificidade e a acurácia do TI em identificar a causa da síncope na amostra foram, respectivamente, 6%, 66% e 40%. CONCLUSÃO: Uma menor atividade parassimpática, medida pela VFC, foi observada nos portadores de CMH com síncope. Não foram encontradas diferenças na reserva vagal e na adaptação hemodinâmica ao estresse ortostático entre os grupos. O TI revelou-se com baixa sensibilidade, especificidade e acurácia para o diagnóstico de síncope inexplicada nessa população. / BACKGROUND: Unexplained syncope is considered a risk factor for sudden death in hypertrophic cardiomyopathy (HCM). Several mechanisms are involved in its pathogenesis, including the difficulty in adaptation of the systemic vascular resistance to exertion and to orthostatic stress, which may be influenced by a dysfunction of the autonomic nervous system. The purposes of this study were to compare the autonomic nervous function in patients with HCM with and without syncope and to assess diagnostic value of the head-up tilting test (HUT) in this population. METHODS: Thirty seven patients were included: 16 with unexplained syncope at routine evaluation and 21 without syncope. The autonomic nervous function was assessed by spontaneous and phenylephrine-induced baroreflex sensitivity (BRS) and by heart rate variability (HRV). Considered HRV variables in time domain were: standard deviation of normal RR intervals (SDNN), root mean square of successive differences (RMSSD), and percentage of adjacent normal RR intervals which differ by at least 50 ms (pNN50), during 24 hours electrocardiogram recording. In frequency domain, high, low and very low frequency bands and the spectrum total power density were considered, both in absolute values and in normalized units, at rest and at 60-degree tilting. Measures of systolic and diastolic blood pressure, beat to beat, and measures of stroke index, cardiac index, and systemic vascular resistance, obtained by impedance cardiography, were compared between the groups, at 0-, 30- and 60-degree tilting. The HUT consisted in exposure to 60º for 40 minutes, or until a positive response. RESULTS: Spontaneous BRS measures were similar between the syncope and non-syncope groups (16.46±12.99 vs 18.31±9.88 ms/mmHg, p=0.464), as well as phenylephrine induced BRS (18.33±9.31 vs 15.83±15.48 ms/mmHg, p=0.521). No differences were found between SDNN values (137.69±36.62 vs 145.95±38.07 ms, p=0.389). The syncope group presented lower values of RMSSD (24.88±10.03 vs 35.58±16.43 ms, p=0.042) and a trend to lower pNN50 (4.51±3.78 vs 8.83±7.98 %, p=0.085) and to lower high frequency component of spectral analyses at rest (637.59±1295.53 vs 782.65±1264.14 ms2, p= 0.075). No differences were observed between the groups in the others parameters analyzed in the frequency domain. Adaptation of hemodynamic variables at different tilting degrees was similar between the groups at the various positions studied. Positive responses to HUT were similar in the two groups (6% in syncope group and 33% in no-syncope group; p=0.053). HUT sensitivity, specificity and accuracy in identifying the cause of syncope in this population were, respectively, 6%, 66% and 40%. CONCLUSION: A lower parasympathetic activity, measured by HRV, was observed in HCM patients with syncope. No differences were found in vagal reserve and in adaptation to orthostatic stress between the groups. HUT showed poor sensitivity, specificity and accuracy in diagnosing unexplained syncope in this population.

O estudo investigou a participação do sistema nervoso simpático ß-adrenérgico sobre a regulação da expressão gene do GLUT4 em músculo vermelho (sóleo) e branco (EDL) no jejum. Foram estudados ratos alimentados livremente, jejuados por 48 horas e sob bloqueio ß1/ß2 ou bloqueio ß1/ß2/ß3 ou sob estímulo ß1/ß2/ß3-adrenérgicos. Os músculos sóleo e EDL foram analisados por Northern e Western Blotting. O jejum diminuiu o peso dos animais, a glicemia, a insulinemia, e aumentou concentração de ácidos graxos livres (AGL). O bloqueio ß1/ß2 aumentou a insulinemia, o bloqueio ß1/ß2/ß3 reduziu a glicemia e o estímulo ß1/ß2/ß3 aumentou AGL. O jejum aumentou mRNA do GLUT4 no sóleo e EDL, os bloqueios ß-adrenérgicos reduziram o mRNA no sóleo e EDL, e o estímulo ß aumentou o mRNA somente no sóleo. O jejum aumentou a proteína GLUT4 no sóleo e nos tratamentos somente reduziu com o bloqueio triplo, no EDL. O jejum aumentou a expressão do gene do GLUT4 em músculo esquelético. A atividade simpática ß-adrenérgica é fundamental para aumentar a expressão do GLUT4 no sóleo e manter no EDL. / The study investigated the participation of ß-adrenergic sympathetic nervous system in the regulation of GLUT4 gene expression in red (soleus) and white (EDL) muscles during fasting. Rats were fasted for 48hours and treated with ß1/ß2-adrenoceptors antagonist or ß1/ß2/ß3-adrenoceptors antagonist or ß1/ß2/ß3-adrenoceptors agonist. Soleus and EDL muscles were analyzed by Northern and Western Blotting. Fasting decreased body weight, glycemia, insulinemia, and increased non esterified free fatty acids (NEFA). The insulinemia increased with ß1/ß2 blockade, glycemia decreased with triple blockade, NEFA increased with ß stimulus. The GLUT4 mRNA increased in soleus and EDL after fasting, and it decreased in soleus and EDL after ß1/ß2 blockade and triple blockade, and increased in soleus after ß stimulus. GLUT4 protein increased in soleus of fasted rats, and decreased with triple blockade in EDL. Fasting increased GLUT4 gene expresion in skeletal muscle. The ß-adrenergic sympathetic activity is essencial to increase GLUT4 expression in soleus and to preserve it in EDL.

Uma das causas da hipertensão está relacionada a alterações de núcleos autonômicos responsáveis pelo controle dos reflexos cardiovasculares, destacando-se o PVN, o NTS e o RVLM. A ANG II, atuando nestes núcleos, participa do controle da PA. Estudos in vitro, demonstraram uma via de sinalização da ANG II que envolve a ativação da PI3K e da Akt. Neste estudo avaliamos as diferenças na atividade da PI3K, através da quantificação da subunidade p85 (PI3K) e da p-Akt por meio de immunoblotting desses núcleos centrais de animais SHR, WKY e Wistar, além da interação da PI3K com os efeitos cardiovasculares da ANG II injetada no PVN de Wistar acordados. A expressão da p85 não diferiu entre os núcleos estudados. No entanto, a p-Akt estava 1,5x mais expressa no PVN de SHR. Ainda, o aumento da PAM promovido pela injeção de ANG II no PVN foi reduzido 5 min após a injeção do inibidor da PI3K, com recuperação da resposta 30 min mais tarde, sugerindo que a via da PI3K está mais ativa no PVN de animais SHR e que a interação das vias ANG II-PI3K está relacionada com a hipertensão. / One cause of the hypertension is associated to changes in autonomic nuclei that control the cardiovascular reflexes. Among these nuclei are PVN, NST and RVLM. The ANG II, acting in these nuclei, contributes to the control of the AP. In vitro studies had demonstrated a signaling pathway of the ANG II that involves the activation of PI3K and Akt. In the present study we evaluated the PI3K activity via expression of p85 (PI3K) and p-Akt, through the immunoblotting of these central nuclei of SHR, WKY and Wistar. Moreover, we evaluated the interaction of PI3K to the cardiovascular effects of ANG II injected into the PVN of awake Wistar. The p85 expression was not different at all autonomic nuclei studied. However, the p-Akt expression was 1.5x higher in the PVN of SHR. Besides, the increase in the MAP elicited by the injection of ANG II into the PVN was reduced 5 min after the blockade of the PI3K, and restored 30 min later, suggesting that PI3K pathway is more activate at the PVN level of SHR and that the interaction between ANG II-PI3K is related to hypertension.

Há diversas evidências epidemiológicas de correlações positivas entre indicadores de morbidade e mortalidade pulmonar e cardiovascular e aumentos na concentração atmosférica de MP2,5 (material particulado fino). O objetivo deste trabalho foi avaliar os efeitos da exposição subcrônica de MP2,5 sobre o tônus cardíaco autonômico, a inflamação pulmonar e sistêmica; o estresse oxidativo e a homeostase sanguínea, após oito semanas de repetidas instilações nasais de suspensão aquosa de MP2,5 da cidade de São Paulo em concentração ambiental. Dividiram-se os animais em dois grupos: salina e MP2,5 e avaliaram-se os seguintes parâmetros: frequência cardíaca (FC), variabilidade da frequência cardíaca (VFC), pressão arterial sistólica (PA), hemograma, contagem de plaquetas e reticulócitos, fibrinogênio plasmático, tempo de protrombina (TP), tempo de tromboplastina parcialmente ativada (TTPA), mielograma, citologia do lavado broncoalveolar (LBA), análise histopatológica e imuno-histoquímica (15-F2tisoprostano e -actina) de pequenas arteríolas pulmonares e coronarianas. Não houve alterações na FC e na PA (p > 0,05). Houve interação estatisticamente significante entre grupos e semanas em relação à VFC. O SDNN (desvio padrão dos intervalos R-R normais), a r-MSSD (raiz quadrada da média dos quadrados das diferenças sucessivas entre intervalos R-R normais adjacentes) e a AF (alta frequência) do grupo MP2,5 aumentaram significativamente na 7ª semana em comparação à 1ª semana (p < 0,05), enquanto a BF (baixa frequência) não se alterou (p > 0,05). A porcentagem de macrófagos no LBA do MP2,5 diminuiu significativamente (p < 0,05). Não se observaram alterações no sangue, mielograma e análise histopatólogica e imuno-histoquímica dos vasos (p > 0,05). Concluiu-se que a exposição subcrônica pela instilação nasal de suspensão aquosa de MP2,5 em concentração ambiental causou inflamação pulmonar tênue e alterou o equilíbrio cardíaco autonômico / There are several epidemiological evidences of positive correlation between indicators of pulmonary and cardiovascular morbidity and mortality and increases of PM2.5 (fine particulate matter) air concentration. The aim of this experiment was to evaluate the effects of subchronic exposure of PM2.5 on cardiac autonomic tone, pulmonary and systemic inflammation, oxidative strees and blood homeotasis of healthy rats after eight weeks of repeated nasal instillations of suspended PM2.5 from Sao Paulo city in environmental concentration. Rats were divided in two groups: saline and PM2.5. The following parameters were evaluated: heart rate (HR), heart rate variability (HRV), systolic blood pressure (BP), hemogram, platelets and reticulocytes count, plasmatic fibrinogen, prothrombin time (PT), activated partial thromboplastin time (APTT), bone marrow cells, bronchoalveolar lavage cells (BAL), histopathological and immunohistochemical analysis (15-F2tisoprostane and -actin) of pulmonary and coronary small arterioles. No changes were detected in HR and BP (p > 0.05). There were a statistically significant interaction between groups and weeks in relation to HRV. SDNN (standard deviation of normal RR intervals), r-MSSD (square root of the mean of the squared differences between adjacent normal RR intervals) and HF (high frequency) of PM2.5 group significantly increased on 7th week compaired to 1st week (p < 0.05), while LF (low frequency) did not alter (p > 0.05). BAL macrophages porcentage of PM2.5 group significantly decreased (p < 0.05). No alterations were observed in blood, bone marrow cells, histopathological and immunohistochemical analysis of vessels (p > 0.05). We concluded that subchronic exposure by nasal instillation of aquous suspension of PM2.5 in environmental concentration caused tenuous pulmonary inflammation and altered cardiac autonomic balance

Parmi les facteurs intervienant dans la régulation et le maintien du fonctionnement d'organes, le système nerveux autonome et la microcirculation jouent un rôle prépondérant. Chez les patients critiques, comme les patients en sepsis, des altérations de la balance sympatho-vagale et de la perfusion tissulaire peuvent survenir et avoir des conséquences majeures en matière de morbidité et mortalité. La mise en oeuvre de méthodes de détection précoces de ces perturbations pourrait donc contribuer à améliorer la survie des patients à risque. En effet, le suivi des paramètres hémodynamiques, comme classiquement réalisé lors de réanimation, peut s'avérer insuffisant pour détecter des altérations de perfusion tissulaire : lors de sepsis, des altérations microcirculatoires peuvent persister en dépit de la normalisation des paramètres macrocirculatoires et sont associées à un mauvais pronostic. Eu égard à la présence de dysfunctions microcirculatoires et du système nerveux autonome chez les patients critiques, ce travail de recherche s'est proposé d'évaluer l’impact de modulateurs du système sympathique sur la balance sympatho-vagale et la microcirculation. Pour ce faire, nous avons travaillé avec des modèles animaux et des animaux admis en centre hospitalier universitaire vétérinaire. Le suivi du système nerveux autonome s'est basé sur un nouvel index de mesure du tonus parasympathique (Parasympathetic Tone Activity ou PTA). En parallèle, la microcirculation a été évaluée par vidéomicroscopie (SDF, Sidestream Dark Field imaging). L'index PTA a démontré une performance correcte pour prédire les réactions hémodynamiques chez les chiens anesthésiés. Il a aussi permis de détecter une altération de la balance sympathique chez les chevaux admis pour une chirurgie de colique ainsi qu’une altération de la microcirculation en dépit des manoeuvres de réanimation. Les études précliniques sur l’impact de la perfusion d’esmolol et de dexmédétomidine dans un modèle porcin septique ont montré que, malgré leurs effets hémodynamiques potentiels, ces agents n’ont pas eu d’effet négatif sur la microcirculation. Ainsi, les résultats de ce travail suggèrent un effet bénéfique des modulateurs du système nerveux sympathique sur la microcicultion mais nécessite d'être confirmé à plus grande échelle / Among the factors involved in the regulation and maintenance of the organs’ functioning, the autonomic nervous system and the microcirculation play a preponderant role. In critical patients, such as septic patients, alterations in the sympathovagal balance and tissue perfusion may occur and have major consequences of morbidity and mortality. The implementation of early detection methods for these disturbances could therefore contribute to improve the survival of patients at risk. Indeed, the monitoring of hemodynamic parameters, as conventionally performed during resuscitation, may be insufficient to detect tissue perfusion alterations: during sepsis, microcirculatory changes may persist despite the normalization of macrocirculatory parameters and are associated with a bad prognosis. With regard to the presence of microcirculatory dysfunctions and autonomic nervous system alterations in critical patients, this research project proposed to evaluate the impact of modulators of the sympathetic system on the sympatho-vagal balance and microcirculation. In order to achieve this, we worked on animal models and animals admitted to the faculty’s veterinary hospital center. Monitoring of the autonomic nervous system was based on a new Parasympathetic Tone Activity (PTA) index. In parallel, the microcirculation was evaluated by videomicroscopy (SDF, Sidestream Dark Field imaging). The PTA index demonstrated a good performance in predicting hemodynamic reactions in anesthetized dogs. It also detected disturbances of the sympathetic balance in horses admitted for colic surgery as well as an alteration of microcirculation despite resuscitation maneuvers. Preclinical studies on the impact of esmolol and dexmedetomidine infusion in a septic swine model showed that, despite their potential hemodynamic effects, these agents did not have a negative effect on the microcirculation. Thus, these findings suggest a beneficial effect of the modulators of the sympathetic nervous system on the microcicultion, however, these resutls should be confirmed on a larger scale

Abstract Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been gaining importance in the treatment of advanced Parkinson's disease. This study was undertaken to evaluate the beneficial effects of bilateral STN stimulation on patient's clinical symptoms and quality of life related to the potential risks and side effects of the treatment. A consecutive series of 42 patients operated on for Parkinson's disease with STN DBS in Oulu University Hospital were included. A subgroup of these patients was evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS), neuropsychological tests, and Health Related Quality of Life (HRQoL) instruments i.e. the Parkinson's Disease Questionnaire (PDQ-39) and the Finnish version of the Nottingham Health Profile (NHP). The costs of the treatment were calculated from the perspective of the health care provider. The possible effects of bilateral STN-operation on cardiovascular autonomic function were analyzed by measuring various time- and frequency domain indexes as well as non-linear indexes of heart rate variability (HRV) from 24-hour EKG recording before and 12 months after the operation. This study showed that STN DBS significantly improves the clinical symptoms and HRQoL of parkinsonian patients. The dyskinesia and clinical fluctuation scores were reduced very significantly in the UPDRS IV subscale. The clinical fluctuations were reduced by 53 %. After DBS best motor response (UPDRS III) scores also improved significantly. The HRQoL measured with both instruments improved significantly. Improvement was seen in the PDQ-39 summary index and the subscales of activities of daily living, emotional well-being, stigma and bodily discomfort. Only communication became worse during the follow-up. There was a statistically significant improvement in the score of the subscales of NHP measuring problems with energy, sleep, emotional reactions and social isolation. One patient died from pulmonary embolism and another contracted a late postoperative intracerebral hemorrhage leading to a permanent deterioration of her neurological condition to the bedridden stage. Other complications were much milder. Clinical improvement and improvement in HRQoL were positively correlated. STN DBS does not influence tonic autonomic cardiovascular regulation. The incremental costs of performing bilateral STN DBS in Finland compared to preoperative medical treatment amounted to an average of 25 591 EUR per patient during the first postoperative year. The majority of parkinsonian patients experienced significant and long lasting relief in their motor symptoms and an improvement in HRQoL following STN stimulation.

Breathing is an automatic process that we hardly pay any attention to in our daily life. As a social species, we interact using body movement, speech and emotion and these actions require modification of the respiratory pattern. While we understood how the respiratory rhythm is generated, we do not have clear evidence on how higher cortical signals modulate the respiratory pattern. The deep cortical structures in the human brain are inaccessible under normal circumstances, and deep brain stimulation electrode recordings offer an opportunity to understand the neurophysiological interactions ofdeeper brain structures. In this thesis, I investigated deep brain stimulation recordings from implanted electrodes in chronic neuropathic pain subjects in the right and left anterior cingulate cortices, the ventral posterior lateral nucleus of the thalamus and periventricular gray region. The objectives of this research were to elucidate the feed-forward mechanisms of volitional breathing, cortical autonomic regulation, and to investigate whether any of the investigated nuclei haveany carbon dioxide-sensitive neurons which may encode respiratory sensation. The results show lateralisation of the cortical autonomic control whereby the left anterior cingulate exhibits increases in beta band activity (30 to 90 Hz) with cognition and vocalisation tasks. Meanwhile, right anterior cingulate activity increases with hyperoxia. Respiration using various carbon dioxide concentrations shows a constant rise in the alpha band (8 to 14 Hz) activity in the PVG which suggests a sensitive, nonspecific neuronal activity related to systemic carbon dioxide levels.

A recuperação da frequência cardíaca pós-exercício (RecFC) é determinada pela reativação vagal e retirada simpática. Essas respostas, por sua vez, são reguladas pela ação integrada dos diversos mecanismos de controle cardiovascular, como o comando central, o mecanorreflexo muscular, o metaborreflexo muscular e a termorregulação. Na hipertensão arterial sistêmica (HAS) ocorre redução da RecFC, refletindo a presença de disfunção autonômica e sugerindo prejuízos nos mecanismos de controle cardiovascular, que precisam ser investigados. Dessa forma, esta tese visou avaliar e comparar a influência dos mecanismos de controle cardiovascular sobre a RecFC e sua regulação autonômica em normotensos (NT) e hipertensos nunca-tratados (HT). Para tanto, 23 homens HT (45±8 anos; 142±8/96±3 mmHg) e 25 NT (43±8 anos; 114±4/77±2 mmHg) realizaram, de forma aleatória, 5 sessões experimentais compostas de: período pré-exercício, 30 min de exercício em cicloergômetro (70% do VO2pico) e 5 min de recuperação. A recuperação diferiu entre as sessões, seguindo os protocolos: a) recuperação inativa (RI) - ausência de movimento; b) recuperação ativa (RA) - manutenção do movimento pelo próprio voluntário; c) recuperação passiva (RP) - manutenção do movimento por força externa; d) recuperação com oclusão (RO) - ausência de movimento e oclusão total da circulação da coxa; e e) recuperação com resfriamento (RR) - ausência de movimento e resfriamento por ventilação. A atividade eletrocardiográfica, a respiração e a pressão arterial foram continuamente registradas. A RecFC foi avaliada por meio do cálculo dos índices: a) RecFC30s, RecFC60s, RecFC300s: i.e., redução da FC após 30s, 60s e 300s de recuperação; b) constante de tempo de curta duração da RecFC (T30) e; c) constante de tempo de longa duração da RecFC (RecFCt). A comparação da RecFC entre RA e RP permitiu avaliar a influência do comando central sobre a RecFC. A RecFC foi mais lenta na RA em comparação à RP (RecFC30s = 11±6 vs. 13±7 bpm, p<0,01), não havendo diferença entre os grupos nessa resposta. A comparação de RP e RI foi utilizada para avaliar o mecanorreflexo. A RecFC foi mais lenta na RP em comparação à RI (T30 = 351±167 vs. 267±128 s, p<0,01) e esse efeito foi maior no grupo HT (+160±154 vs. +32±147 s, p=0,03). A comparação de RI e RO foi utilizada para avaliar o metaborreflexo. A RecFC foi mais lenta na RO que na RI (RecFC300s = 25±14 vs. 37±10 bpm, p<0,01), e esse efeito foi maior nos HT (-16±11 vs. -8±15 bpm, p=0,05). Por fim, a comparação de RI e RR foi utilizada para avaliar a termorregulação. A RecFC foi mais rápida na RR em comparação à RI (RecFC300s = 39±12 vs. 37±10 bpm, p<0,01), não havendo diferença entre os grupos nessa resposta. Conclui-se, que a RecFC é influenciada pela atuação do comando central, mecanorreflexo muscular, metaborreflexo muscular e termorregulação. Em adição, a redução na RecFC na HAS está relacionada, pelo menos em parte, à maior sensibilidade do mecanorreflexo e do metaborreflexo musculares / Post-exercise heart rate recovery (HRR) is determined by vagal reactivation and sympathetic withdrawal. These responses are regulated by the integrated action of several cardiovascular control mechanisms, such as central command, muscle mechanoreflex, muscle metaboreflex and thermoregulation. The reduction in HRR occurs in hypertension, which indicates the presence of autonomic dysfunction and suggests impairments of the cardiovascular control mechanisms that need to be studied. Thus, this thesis assessed and compared the influence of the cardiovascular control mechanisms on HRR and its autonomic regulation in normotensives (NT) and never-treated hypertensives (HT). For this purpose, 23 HT (45±8 years; 142±8/96±3 mmHg) and 25 NT (43±8 years; 114±4/77±2 mmHg) men performed, in a random order, 5 experimental sessions composed by: pre-exercise period, 30 min of cycle ergometer exercise (70% VO2peak) and 5 min of recovery. The recovery was different between the sessions, as follow: a) inactive recovery (IR) - absence of movement; b) active recovery (AR) - maintenance of movement by the own voluntary; c) passive recovery (PR) - maintenance of movement by an external force; d) occlusion recovery (OR) - absence of movement and total circulatory occlusion of hips\' circulation; and e) cooling recovery (CR) - absence of movement and cooling using a fan. Electrocardiographic activity, respiration and blood pressure were continuously registered. HRR was assessed by the calculation of the following indices: a) HRR30s, HRR60s and HRR300s: i.e. heart rate reduction after 30s, 60s and 300s of recovery; b) short-term time-constant of HRR (T30); and c) long-term time-constant of HRR (HRRt). The comparison of HRR between AR and PR allowed the assessment of the central command influence on HRR. HRR was slower in AR in comparison with PR (HRR30s = 11±6 vs. 13±7 bpm, p<0.01), and there were no difference between the groups in this response. The comparison of HRR between PR and IR allowed the assessment of the mechanoreflex influence on HRR. HRR was slower in PR in comparison with IR (T30 = 351±167 vs. 267±128 s, p<0.01), and this effect was greater in the HT (+160±154 vs. +32±147 s, p=0.03). The comparison of HRR between OR and IR allowed the assessment of the metaboreflex influence on HRR. HRR was slower in OR in comparison with IR (HRR300s = 25±14 vs. 37±10 bpm, p<0.01), and this effect was greater in the HT (-16±11 vs. -8±15 bpm, p=0,05). Finally, the comparison of HRR between IR and CR allowed the assessment of the thermoregulation influence on HRR. HRR was accelerated in CR in comparison with IR (HRR300s = 39±12 vs. 37±10 bpm, p<0.01), and there were no difference between the groups in this response. In conclusion: HRR is influenced by the action of central command, muscle mechanoreflex, muscle metaboreflex and thermoregulation. In addition, the reduction in HRR in hypertension is, at least in part, related to a greater sensitivity of the muscle mechanoreflex and metaboreflex