A Síndrome Antifosfolípide (SAF) primária está associada com o risco aumentado de doenças cardiovasculares e mortalidade. A capacidade aeróbia e o controle autonômico cardíaco também estão associados a esses riscos. Objetivos: Avaliar a capacidade aeróbia e o controle autonômico cardíaco em pacientes com SAF primária. Métodos: Treze mulheres com SAF e treze controles saudáveis pareados por idade, sexo e índice de massa corporal foram incluídos no estudo. Ambos os grupos eram sedentários e não estavam em uso de medicações cronotrópicas, antidepressivas e hipolipemiantes. Todos os indivíduos realizaram o teste ergoespirométrico em esteira. A capacidade aeróbia foi avaliada através do pico do consumo de oxigênio (VO2pico), tempo no limiar anaeróbio ventilatório (LAV) e no ponto de compensação respiratória (PCR) e tempo no pico de esforço, enquanto o controle autonômico do coração foi avaliado através da reserva cronotrópica (RC) e frequência cardíaca na recuperação no primeiro e segundo minutos após o exercício (FCR1min e FCR2min, respectivamente). Resultados: Todos os índices de capacidade aeróbia estavam reduzidos nos pacientes com SAF primária em comparação com os controles saudáveis: VO2pico (30,2 ± 4,7 vs. 34,6 ± 4,3 mL.kg-1.min-1 P = 0,021), tempo no LA (3,0 ± 1,5 vs. 5,0 ± 2,0 min; P = 0,016), tempo no PCR (6,5 ± 2,0 vs. 8,0 ± 2,0 min; P = 0,050), tempo no pico de esforço (8,5 ± 2,0 vs. 11,0 ± 2,5 min; P = 0,010). As FCR1min (22 ± 9 vs. 30 ± 7 bpm; P = 0,032) e FCR2min (33 ± 9 vs. 46 ± 8 bpm; P = 0,002) foram menores nos pacientes com SAF em comparação com os controles saudáveis mas a RC não foi significativamente diferente (P = 0,272). Dessa forma, observamos uma diminuição na capacidade aeróbia e no controle autonômico nos pacientes com SAF / Primary antiphospholipid syndrome (PAPS) is associated with increased risk of cardiovascular disease and mortality. Aerobic capacity and cardiac autonomic control are also associated with these risks. Objective: To assess aerobic capacity and cardiac autonomic control in PAPS patients. Methods: Thirteen women with PAPS and 13 healthy controls matched for age, gender, and body mass index were enrolled for the study. Both groups were sedentary and were not under chronotropic, antidepressants and hypolipemiant drugs. All subjects performed a treadmill graded maximal exercise. Aerobic capacity was assessed by peak oxygen uptake (VO2peak), time at anaerobic ventilatory threshold (VAT) and respiratory compensation point (RCP), and time-to-exhaustion, whereas cardiac autonomic control by chronotropic reserve (CR) and heart rate recovery of the first and second minutes after graded exercise (HRR1min and HRR2min, respectively). Results: All aerobic capacity indexes were reduced in PAPS patients than healthy subjects: VO2peak (30.2 ± 4.7 vs. 34.6 ± 4.3ml.kg-1.min-1, P = 0.021), time at LAV (3.0 ± 1.5 vs. 5.0 ± 2.0 min, P = 0.016), time at RCP (6.5 ± 2.0 vs. 8.0 ± 2.0 min, P = 0.050), time-to-exhaustion (8.5 ± 2.0 vs. 11.0 ± 2.5 min, P = 0.010). HRR1min (22 ± 9 vs. 30 ± 7bpm, P = 0.032) and HRR2min (33 ± 9 vs. 46 ± 8bpm, P = 0.002) were delayed in PAPS patients compared to healthy controls but CR was not significantly different (P = 0.272). In conclusion, an impaired aerobic capacity and cardiac autonomic control was identified in PAPS

Um estudo morfoquantitativo foi realizado no plexo intramural de bexigas urinárias de cobaias (Cavia porcelus) jovens (GI) e idosas (GII). As bexigas foram submetidas aos métodos da NADH-diaforase e da detecção da atividade da acetilcolinesterase. Os neurônios intramurais apresentaram-se isolados ou reunidos em gânglios de pequeno a grande número entre os feixes musculares lisos que constituem o músculo detrusor. O número médio de neurônios NADH-diaforase positivos por bexiga urinária foi de 1.433±187 em GI e de 1.107±120 em GII. Foram observados neurônios arredondados ou ovalados em ambos os grupos, porém o perfil citoplasmático apresentou-se com aspecto relativamente denteado em GII. Em relação a colinesterase, os neurônios de GI apresentaram-se com marcação menos intensa do que em GII. A área média do perfil celular dos neurônios intramurais NADH-diaforase positivos foi de 711,01±28,14µm2 em GI e de 873,30±60,25µm2 em GII, sendo esta a principal diferença morfológica encontrada entre os grupos. / A morphoquantitative study was carried on intramural plexus of the urinary bladder of the young (GI) and old (GII) guinea-pigs (Cavia porcelus). The specimens were stained with NADH-diaphorase and AChE methods. The intramural neurons were observed both isolated or in small and large clusters lying between the bundles of smooth muscle fibers of the detrusor muscle. The mean number of NADH-diaphorase staining neurons per urinary bladder was 1.433±187 in the GI and 1.107±120 in the GII. In both groups, round or elongated neurons were observed. The citoplasmatic contour was indented the animals of GII. The AChE method evidenced intensely reactive neurons in GII when compared with those of the GI. The mean of neuronal profiles was 711,01±28,14mm2 in the GI and 873,30±60,25mm2 in the GII. This observation was the main morphological difference between the GI and GII.

O presente trabalho tem como objetivos avaliar a resposta da freqüência cardíaca (FC) e de sua variabilidade nas condições de repouso e em exercício físico dinâmico; determinar o limiar de anaerobiose a partir da análise das respostas de FC durante o exercício físico pelos modelos matemáticos e estatísticos autorregressivos-integrados-médias móveis (ARIMA) e semiparamétrico (SMP) e pelos índices de variabilidade da freqüência cardíaca (VFC); comparar o grau de correlação entre as três metodologias de análise na detecção de alterações no padrão de resposta da FC como indicador do limiar de anaerobiose (LA). Foram estudados doze voluntários com idade em mediana de 42 anos, considerados ativos e saudáveis, a partir dos resultados da avaliação clínica, cardiovascular e do eletrocardiograma (ECG) em repouso e durante teste de esforço físico dinâmico contínuo do tipo degrau (TEFDC-D). O protocolo experimental consistiu de teste de esforço físico dinâmico descontínuo do tipo degrau (TEFDD-D), com potências progressivas de 10 em 10 watts (W) sendo que a potência inicial foi de 25W. Os intervalos RR (IRR) e a FC, captados a partir dos registros do ECG em tempo real, batimento a batimento, foram obtidos utilizando-se um programa de processamento de sinais. Os dados foram captados na condição de repouso por um período de 900 s na posição supina, 900 s na posição sentada e sentado no cicloergômetro durante 60 s em repouso, 360s em exercício e 60s em recuperação. Foram calculadas: as médias da FC; os índices de RMSSD dos IRR de repouso e em exercício; tempo de variação da FC (t/DFC t1 – t0 ) em segundos onde t1 eqüivale ao instante em que ocorreu o maior valor da FC no período entre 0 (t0) e 20 s do início do exercício físico e a variação da FC no mesmo intervalo. Para determinar o LA a partir da análise das respostas de FC durante o exercício físico utilizou-se os modelos matemáticos autorregressivos-integrados- médias móveis (ARIMA) e o modelo SMP. Para análise estatística utilizou-se o teste de Wilcoxon, e nas comparações múltiplas o teste de Friedman, seguido do teste de Dunn, e o de correlação de Spearman, com nível de significância de 5%.A FC em repouso na posição sentada foi superior a da posição supina (p<0,05), já a VFC foi semelhante. O t/DFC t1 – t0 e o DFC (bpm) apresentou diferenças estatisticamente significantes nas potências realizadas pelos voluntários. Os índices de VFC durante o TEFDD-D reduziram com o incremento de potência apresentando diferenças estatisticamente significantes (p<0,05), para o RMSSD nas potências de 55 e 60 W em relação ao repouso sentado e em relação as potências de 25 e 35 W. O nível do LA foi em 60 W com uma FC de 97 bpm e em 55 W com uma FC de 97 bpm, determinados pelo modelo ARIMA e pelo modelo SMP, respectivamente (p>0,05). Na comparação dos índices de RMSSD dos IRR no nível de potência do LA determinado pelos modelos de análise, não observamos diferenças significantes (p>0,05). O coeficiente de correlação entre os índices de RMSSD do modelo SMP vs ARIMA foi rs= 0,82 com p<0,05; entre as potências dos dois modelos foi: rs = 0,72, p < 0,05 e entre a FC foi rs = 0,87, p < 0,05. A análise da VFC, a partir do índice de RMSSD foi sensível na identificação de alterações da modulação autonômica sobre o nódulo sinusal. O aumento da FC com concomitante redução da VFC, associado ao incremento de potência sugere uma menor participação da atuação vagal e predomínio da atividade simpática sobre o nó sinusal. As três metodologias de análise utilizadas neste trabalho mostraram respostas similares, apresentando uma correlação estatisticamente significante, sendo portanto adequadas para detectar o ponto de mudança da resposta da FC concomitante ao achatamento da VFC como indicativo do limiar de anaerobiose. / The objectives of the present study were to assess the heart rate (HR) response and its variability under resting conditions and during dynamic physical exercise, to determine the anaerobic threshold from the analysis of the HR responses during physical exercise using the autoregressive-integrated-moving average (ARIMA) and semi-parametric (SMP) mathematical and statistical models and the indices of heart rate variability (HRV), and to compare the degree of correlation between the three methods of analysis for the detection of changes in the pattern of HR response as an indicator of anaerobic threshold (AT). The study was conducted on 12 volunteers (median age: 42 years) considered to be active and healthy on the basis of clinical and cardiovascular evaluation of resting electrocardiogram (ECG) and of ECG during a continuous dynamic physical effort test of the step type (CDPET-S). The experimental protocol consisted of a discontinuous DPET-S (DDPET-S) with progressive 10 Watts increments starting from and initial power of 25 Watts. RR intervals (RRI) and HR obtained from ECG recordings in real time, beat to beat, were recorded using a signal processing system. The data were obtained in the resting condition for a period of 900 s with the subject in the supine position, for 900 s in the sitting position ,and with the subject sitting on the bicycle ergometer for 60 s at rest, for 360 s while exercising and for 60 s during recovery. We calculated mean HR, RMSSD and RRI indices at rest and during exercise, HRV time (t/DHR t1 – t0 ) in seconds, where t1 is the instant when the highest HR value occurred during the period between 0 (t0) and 20 s after the beginning of physical exercise, and HR variation (DHR)during the same interval. To determine AT from the analysis of the HR responses during physical exercise we used the ARIMA and SMP models. Data were analyzed statistically by the Wilcoxon test and by the Friedman test for multiple comparisons followed by the Dunn test. Correlation was calculated by the Spearman test and the level of significance was set at 5% in all analyses. Resting HR in the sitting position was higher than in the supine position (p<0.05), whereas HRV was similar.t/DHR t1 – t0 and DHR (beat/min) presented statistically significant differences at the powers reached by the volunteers. The HRV indices during the DDPET-S were reduced with increasing power, showing statistically significant differences (p<0.05) for RMSSD at the powers of 55 and 60 Watts compared to sitting rest and compared to the powers of 25 and 35 Watts. The AT level determined by ARIMA was at 60 Watts, with HR of 97 beat/min, and the AT level determined by SMP was at 55 Watts, with HR of 97 beat/min (p>0.05). Comparison of the RMSSD indices of the RRI at the power level of AT determined by the analysis models did not show significant differences (p>0.05). The correla tion coefficient between the RMSSD indices of the SMP model vs ARIMA was rs= 0.82, with p<0.05; between the powers of the two models it was rs = 0.72, p < 0.05, and between HR of the two models it was rs = 0.87, p < 0.05. HRV analysis from the RMSSD index was sensitive for the identification of changes in autonomic modulation of the sinus node. The increase in HR with a concomitant reduction in HRV, together with the increment in power suggests a lower participation of vagal activity and a predominance of sympathetic activity in the sinus node. The three methods used for analysis in the present study showed similar responses and were strongly correlated and therefore are adequate to detect the point of change in the HR response concomitant with HRV flattening as an indication that AT.

Este trabalho teve por objetivo avaliar a modulação autonômica da freqüência cardíaca (FC) durante o repouso, nas posições supina e sentada, e durante teste de esforço físico dinâmico descontínuo do tipo degrau (TEFDD-D) em mulheres jovens e pós-menopausa sem (PMSRH) e com reposição hormonal (PMCRH); determinar o limiar de anaerobiose (LA) a partir da análise das respostas de FC e pela análise dos índices de RMSSD (raiz quadrada da média dos quadrados das diferenças entre os intervalos R-R normais sucessivos), em milissegundos (ms), e comparar o grau de correlação entre estas duas metodologias de análise. Foram estudadas 11 jovens (24 ± 2,77 anos), 13 PMSRH (57 ± 5,28) e 9 PMCRH (55 ± 5,40 anos). O TEFDD-D foi realizado em cicloergômetro, sendo iniciado com a potência de 15 W e com incrementos de 5 em 5 W. A FC (bpm) e os intervalos R-R (ms) foram captados em tempo real, por um período de 360s em repouso, em cada posição, e durante 60s em repouso sentado no cicloergômetro, 240s em exercício e 60s em recuperação, em cada potência do TEFDD-D. Foram calculados as médias da FC (bpm) e os índices de RMSSD dos intervalos R-R (ms) para as condições de repouso e durante 180s do exercício nas potências estudadas; cálculo da variação da FC (bpm) no início do exercício e do tempo (s) desta variação. A determinação do LA foi feita pelo ajuste do modelo matemático e estatístico semiparamétrico (SPM) aos dados de FC e pelos índices de RMSSD dos intervalos R-R (ms). Os testes estatísticos utilizados foram: Wilcoxon, Kruskall-Wallis, Friedman, Dunn e o teste de correlação de Spearman, nível de significância de 5%. Durante o repouso, as jovens apresentaram valores dos índices de RMSSD significativamente (p<0,05) superiores em relação aos outros 2 grupos. As variações da FC das jovens no início do exercício foram maiores que as dos grupos PMSRH e PMCRH, enquanto que o tempo de variação da FC foi similar entre os 3 grupos. Na transição do repouso para o exercício, a FC aumentou progressivamente, enquanto que a variabilidade da freqüência cardíaca (VFC) diminuiu. Na comparação intergrupo dos índices de RMSSD, obtidos em cada nível de potência, foi observada diferença significativa (p<0,05) apenas em 35W. Tanto pelo modelo SPM, como pela análise dos índices de RMSSD, as jovens atingiram o LA em potências superiores comparativamente as PMSRH e PMCRH. Os grupos PMSRH e PMCRH apresentaram resultados similares. Não foram observadas diferenças significativas (p>0,05) na comparação dos 2 métodos. O teste de correlação de Spearman mostrou uma associação significativa (p<0,05) entre os mesmos. Estes dados sugerem que após a menopausa ocorre uma diminuição da modulação vagal sobre o coração tanto em repouso como durante o exercício físico, decorrente do processo do envelhecimento e da redução da capacidade física. A terapia de reposição hormonal não teve nenhuma influência sobre os resultados. As duas metodologias de análise do LA se mostraram similares, sugerindo que a mudança de inclinação da resposta da FC ocorre em níveis de esforço em que a VFC se encontra significativamente reduzida. / The objectives of the present study were to assess the autonomic modulation of the heart rate (HR) at rest, in the supine and sitting position, and during a step type discontinuous dynamic physical effort (STDDPE) in young and postmenopausal women not receiving (PMWtHR) and receiving hormonal replacement treatment (PMWHR); to determine the anaerobiosis threshold (AT) based on the analysis of HR response and the RMSSD indices (square root of the mean squared differences of successive R-R intervals), in milliseconds (ms), and to compare the degree of correlation between these two analysis methodologies. The study was conducted on 11 young women (24 ± 2.77 years), 13 PMWtHR (57 ± 5.28) and 9 PMWHR (55 ± 5.40 years). The STDDPE was performed on a bicycle ergometer at an initial power of 15 W, followed by power increments of 5 W. HR (bpm) and R-R intervals (ms) were obtained in real time over a period of 360 s under resting conditions in each position, during 60 s in the sitting rest position on the bicycle ergometer, 240 s during exercise and 60 s during recuperation at each STDDPE power. Mean HR (bpm) and RMSSD indices of the R-R intervals (ms) were calculated for the resting condition and during 180 s of exercise in the powers studied; the HR variation (bpm) and its time (s) were also calculated in the beginning of exercise. AT was determined by the semiparametric mathematical and statistical model (PMS) and by the RMSSD indices of the R-R intervals (ms). Data were analyzed statistically by the Wilcoxon, Kruskal-Wallis, Friedman, Dunn and Spearman correlation tests, with the level of significance set at 5%. During rest, young women presented significantly higher RMSSD indices (p<0.05) than the other 2 groups. The HR variations in young women in the beginning of the exercise were higher than the ones from the PMWtHR and PMWHR groups, whereas HR variations time was similar for the 3 groups. During the transition from rest to exercise HR increased progressively and HRV decreased. Intergroup comparison of RMSSD indices, obtained in each level of power, showed a significant difference (p<0.05) only at 35 W power. On both PMS model and RMSSD indices analysis, young women reached AT at a higher power compared to PMWtHR and PMWHR groups. The PMWtHR and PMWHR groups presented similar results. No significant differences (p>0.05) were observed when the methods were compared. The Spearman correlation test showed a significant association (p<0.05) between methods. These data suggest that after menopause there is a decrease in vagal modulation of the heart both at rest and during physical exercise due to the aging process and the reduction in physical capacity. Hormonal replacement therapy had no effect on the results. Both methodologies of AT analysis were similar, suggesting that the change in the HR response occurs in levels of effort in which the HRV is significantly reduced.

A doença arterial coronariana (DAC) pode alterar o balanço simpato-vagal do Sistema Nervoso Autônomo (SNA) e aumentar os riscos de arritmias fatais e morte súbita. O exercício físico pode reverter essa condição, porém poucos estudos analisam o ajuste hemodinâmico ao exercício dinâmico resistido, especialmente em portadores de DAC. Além disso, exercícios de membros superiores podem induzir diferentes repostas comparado aos de membros inferiores, porém os estudos comparando os dois tipos de exercícios são escassos. O objetivo do estudo foi analisar as respostas cardiovasculares no exercício resistido de membros superiores e compará-las com o exercício resistido de membros inferiores, em idosos saudáveis e em portadores de DAC. Para a realização do estudo, foram selecionados 20 indivíduos do sexo masculino, sendo 10 idosos saudáveis e 10 idosos portadores de DAC, não etilistas, não tabagistas, e sem distúrbios respiratórios, neurológicos, metabólicos e articulares. Foram realizados: teste de 1RM em exercício resistido no supino inclinado e no leg-press 45°; teste de esforço físico dinâmico resistido com diferentes percentuais de 1RM, com carga inicial de 10% da 1RM e increntos de 10% da 1RM, e a partir de 30% os incrementos passaram a ser de 5% da 1RM. No supino inclinado, houve diminuição significativa do índice rMSSD a partir de 30% da 1RM (GC: de 20±2 ms para 11 ±3 ms; GDAC: de 19±3 ms para 9±1 ms) em ambos os grupos, semelhantemente ao índice SD1 (GC: de 14±2 ms para 8±1; GDAC: 14±2 ms para 7±1 ms). O índice RMSM se manteve sem diferenças entre as cargas no grupo controle (GC) (de 28±3 ms para 45±9 ms), porém aumentou significativamente no grupo DAC (GDAC)(22±2 ms para 79±33 ms). A FC aumentou significativamente a partir de 30% da 1RM em ambos os grupos (GC: de 69±3 bpm para 93±6 bpm; GDAC: 59±3 bpm para 75±4 bpm). No leg-press 45º, houve diminuição do índice rMSSD a partir de 30% da 1RM em ambos os grupos (GC: 29±5 ms para 12±2 ms; GDAC: 28±4 ms para 18±3 ms). O índice SD1 diminuiu no GC a partir de 30% da 1RM (de 23±4 mas para 7±1) e no GDAC a partir de 20% da 1RM (de 16±3 para 11±1). O índice RMSM diminuiu a partir de 30% da 1RM no GC (34±5 ms para 14±3 ms) e aumentou a partir de 35% da 1RM no GDAC (28±4 ms para 43±5 ms). A FC aumentou a partir de 30% da 1RM no GC (65±3 bpm para 92±4 bpm) e a partir de 35% da 1RM no GDAC (61±1 para 76±3). Comparando as variáveis entre os equipamentos, observaram-se menores valores do índice SD1 no GDAC a partir de 35% da 1RM no supino. Também se observaram maiores valores do índice RMSM no GDAC a partir de 30% da 1RM no supino inclinado. Como conclusão, pode-se inferir que houve diminuição parassimpática e aumento da modulação simpática a partir de 30% da 1RM em ambos os equipamentos, sendo que o supino inclinado produziu marcada atenuação parassimpática associada a maior modulação simpática. / Coronary artery disease (CAD) can alter the balance of the sympatho-vagal autonomic nervous system (ANS) and increase the risk of fatal arrhythmias and sudden death. Exercise can reverse this condition, but few studies analyze the hemodynamic adjustment to dynamic resistance exercise, especially in patients with CAD. In addition, upper exercise may induce different responses compared with the lower limbs, but studies comparing the two conditions of resistance exercise are scarce. The objective of the study was to assess the cardiovascular responses in resistance of the upper and compare them with the lower limb resistance exercise in healthy elderly and in patients with CAD. We selected 20 males, 10 healthy elderly and 10 elderly patients with CHD, non-alcohol drinkers, non-smokers, and without respiratory, neurological and metabolic diseases. Were performed: 1RM test in the bench press inclined and leg-press 45 °, and an incremental dynamic resistance test different percentages of 1RM, with initial load of 10% of 1RM and increments of 10% of 1RM, and from 30 % increments was 5% of 1RM. On the bench press inclined, there was significant decrease in RMSSD index from 30% of 1RM (CG: 20 ± 2 ms to 11 ± 3 ms; GDAC: 19 ± 9 ms to 3 ± 1 ms) in both groups, similarly SD1 index (CG: 14 ± 2 to 8 ± 1 ms; GDAC: 14 ± 2 ms to 7 ± 1 ms). The RMSM index remained no differences between the loads in the control group (CG) (28 ± 3 ms to 45 ± 9 ms), but increased significantly in the CAD group (GDAC) (22 ± 2 ms to 79 ± 33 ms). The HR increased significantly from 30% of 1RM in both groups (CG: 69 ± 3 bpm to 93 ± 6 bpm; GDAC: 59 ± 3 bpm to 75 ± 4 bpm). In the leg-press 45º, the RMSSD index decreased from 30% of 1RM in both groups (CG: 29 ± 5 ms to 12 ± 2 ms; GDAC: 28 ± 4 ms to 18 ± 3 ms). The SD1 index decreased in GC from 30% of 1RM (23 ± 4 ms to 7 ± 1 ms) and GDAC from 20% of 1RM (16 ± 3 ms to 11 ± 1 ms). The RMSM index decreased from 30% of 1RM in the GC (34 ± 5 ms to 14 ± 3 ms) and increased from 35% of 1RM in the GDAC (28 ± 4 ms to 43 ± 5 ms). The HR increased from 30% of 1RM in the GC (65 ± 3 bpm to 92 ± 4 bpm) and from 35% of 1RM in the GDAC (61 ± 1 to 76 ± 3). Comparing the variables between the equipment, there were lower values for SD1 from GDAC in 35% of 1RM on the bench press. Also observed higher values in the index RMSM in GDAC from 30% of the 1RM bench press inclined. It can be inferred that decreased parasympathetic and increased in sympathetic modulation from 30% of 1RM in both equipments, and the bench press inclined produced marked attenuation in parasympathetic modulation with an increased in sympathetic modulation.

Le système nerveux autonome (SNA) contribue de façon importante aux régulations des fonctions cardiovasculaires. Pendant des décennies, les chercheurs ont essayé de comprendre comment la variabilité de la fréquence cardiaque (VFC) et le gain du baroréflexe cardiaque pouvaient être utilisés comme marqueurs significatifs du contrôle neurovégétatif cardiaque, et parfois de son altération. L'objectif général de cette thèse est de mieux comprendre le rôle du SNA dans la modulation et les adaptations des fonctions cardiaques et vasculaires. Le projet comprenait quatre études.Dans la première étude, nous avons analysé les effets de l'accélération gravitationnelle graduées sur la régulation neurovégétative de la fréquence cardiaque et de la vasomotricité artériolaire. Dans ces expositions expérimentales des variables cardiovasculaires et respiratoires ont été modifiées de façon spécifique. Nos résultats ne sont pas compatibles avec la mise en jeu d’une régulation sympathique au niveau cardiaque en situation d’hypergravité brève. Nous avons supposé que seule la branche sympathique du SNA était active durant une exposition à une accélération de gravité élevée. La réponse adaptative de la vasomotricité artérielle vasculaire est observée en condition de grande décharge des barorécepteurs. Notre deuxième travail eu pour objet l'effet de la dénervation pulmonaire sur la VFC, et a donc été conduit chez des patients ayant subi une greffe pulmonaire complète. Le greffon n'étant plus relié au SNA, il s'agit d'un excellent modèle expérimental pour l'étude de la régulation cardiovasculaire en l’absence de modulation de l'activité cardiaque par des afférences nerveuses pulmonaires parasympathiques et/ou sympathiques. Puisque la VFC dans les hautes fréquences est reconnue comme largement déterminée par le profil ventilatoire, on s’attend à ce que la composante à haute fréquence de la VFC soit absente chez les sujets transplantés bi-pulmonaires. Les résultats montrent que cette dénervation pulmonaire implique une forte réduction de la VFC totale et dans les deux bandes de fréquence étudiées, hautes et basses. Cela indique donc qu’une large contribution de la modulation nerveuse de la VFC répond aux afférences pulmonaires. La sensibilité du baroréflexe est réduite. Le rapport plus élevé entre les basses et les hautes fréquences traduit une réduction de puissance totale principalement due à la diminution de la composante haute fréquence. Ces résultats montrent que les afférences pulmonaires contribuent largement à la à la modulation neurovégétative de la composante à hautes fréquences de la VFC. La variabilité de la pression artérielle est beaucoup moins modifiée que celle de la VFC par la transplantation bipulmonaire, ce qui met en évidence que les afférences pulmonaires contribuent spécifiquement à la modulation de la VFC. Cette observation est un argument fort pour reconnaître des voies de régulation différentes pour les variabilités de fréquence cardiaque d’une part et de pression artérielle d’autre part. Le troisième article traite des effets sur la modulation cardiovasculaire de blocages pharmacologiques du SNA sur les régulations de fréquence cardiaque et de vasomotricité périphérique, au repos et pendant l'exercice. / Autonomic nervous system (ANS) and cardiovascular regulation are closely linked. For decades, researches have tried to understand how heart rate variability (HRV) and baroreflexes can be used as significant markers of the autonomic nervous control, and sometimes of its impairments. The general aim of this thesis is to gain further insights into the role of ANS in modulating cardiac and vascular functions. The project consisted of four studies.In the first study, we analysed the effects of gravitational acceleration on cardiovascular autonomic control. This special condition showed interesting results for cardiorespiratory variables. Our results did not agree with the notion of sympathetic up-regulation in hypergravity. We speculated that only the sympathetic branch of the ANS might have been active during elevated gravitational acceleration exposure. Furthermore, the vascular response occurred in a condition of massive baroreceptor unloading.Our second work targeted the effect of lung denervation on HRV in bilateral lung transplant recipients. As the graft is no longer connected to the ANS, this is an excellent experimental model for the study of cardiovascular regulation without modulation of heart activity by parasympathetic and/or sympathetic lung afferents. The hypothesis was that the modulation of the high frequency component of HRV by the breathing frequency is mediated by the ANS. This hypothesis would be supported by the results if the high frequency component of HRV is suppressed in bilateral lung transplant recipients. Lung denervation implied strong HRV reduction, all indices being decreased, indicating that neural modulation from lung afferents contributes largely to HRV. Baroreflex sensitivity was reduced. The higher low-versus-high frequency ratio implied that the total power drop was mostly due to the high frequency component, indicating that neural modulation from lung afferents largely contributes to the high frequency component of HRV. The changes in blood pressure variability were smaller than those in HRV, suggesting that the effects of lung denervation were specific to HRV modulation. This finding confirms that blood pressure variability and HRV are under different control mechanisms.The third article concerns the effects of autonomic blockades on cardiovascular modulation, at rest and during exercise. We hypothesized that HRV should decrease with vagal or sympathetic blockades, and disappear during simultaneous blockade of both ANS branches. The results suggest that the parasympathetic outflow to the heart is the main determinant of HRV, while the role of the sympathetic branch is less important. Indeed, sympathetic blockades failed in changing HRV indices at rest, indicating that a selective blockade of cardiac ß-adrenergic receptors has no effects on spontaneous heart rate oscillations. These effects are specific to HRV, as the effects observed on blood pressure variability are indirectly related to the action of the administered drugs. The changes in baroreflex sensitivity were consistent with the changes in arterial blood pressure variability, suggesting that baroreflexes may modulate the LF power of arterial blood pressure.

L’objectif de ce travail de thèse était d’évaluer le bénéfice d’une activité physique régulière sur le syndrome d’apnées-hypopnées obstructives du sommeil (SAHOS). Pour répondre à notre objectif, cinq études ont été conduites pendant cette thèse et seront présentées au cours de ce manuscrit. Ces études se sont déroulées dans deux contextes de pratique distincts : un contexte associatif au sein de la Fédération Française d’Éducation Physique et de Gymnastique Volontaire (FFEPGV) et un contexte hospitalier au sein de l’Unité de réhabilitation cardio-respiratoire du CHU de Saint-Etienne. Notre étude principale, l’étude EXESAS, a évalué le bénéfice d’un programme d’activité physique pratiqué au sein de la FFEPGV (programme NeuroGyV™) dans une étude contrôlée randomisée incluant 96 patients avec un SAHOS modéré et âgés de 40 à 80 ans. Nous avons montré que neuf mois de ce programme, incluant trois heures d’activité physique par semaine, permettait de « guérir » 58% des patients du groupe exercice alors que seulement 20% des patients du groupe contrôle ayant bénéficié de conseils diététiques et de recommandations de bonne pratique en activité physique étaient considérés comme guéris (index d’apnées-hypopnées [IAH] < 15 évènements/heure). A l’issue du programme, les patients du groupe exercice amélioraient également leur qualité de vie et réduisaient leur somnolence. Au-delà de l’amélioration de l’IAH, nous avons mis en évidence une augmentation de la consommation maximale d’oxygène, suggérant une réduction du risque cardiovasculaire. L’étude EXESAS s’est par ailleurs intéressée à l’effet du programme NeuroGyV™ sur l’activité du système nerveux autonome (SNA) mesurée par la variabilité de fréquence cardiaque (VFC). Il a été montré que l’activité du SNA était préservée chez les patients SAHOS ayant bénéficié du programme d’activité physique. En revanche, le groupe contrôle présentait quant à lui une charge hypoxémique plus importante et une variabilité de fréquence cardiaque diminuée, suggérant que le SAHOS et le risque cardiovasculaire associé s’aggravaient spontanément en l’absence d’une activité physique régulière. Le screening de l’étude EXESAS a permis de réaliser un abstract sur le choix du questionnaire de dépistage du SAHOS le plus pertinent en population générale. Nous avons alors montré que le questionnaire STOP-BANG avait une meilleure sensibilité que le questionnaire de Berlin et qu’il devrait être privilégié en dépistage clinique même si sa spécificité reste faible.Enfin, nos travaux de recherche en réhabilitation cardiaque ont permis de confirmer le bénéfice du réentrainement à l’effort sur la sévérité du SAHOS et le rééquilibrage du SNA chez des patients coronariens. Par contre, les résultats préliminaires de l’étude RICAOS ont révélé que le renforcement des muscles inspiratoires chez les patients coronariens souffrant d’un SAHOS modéré n’apportait pas de bénéfice supplémentaire par rapport à un programme de réhabilitation cardiaque classique.En conclusion, l’activité physique régulière réduit efficacement la sévérité du SAHOS chez des patients avec ou sans antécédents cardiaques. Les résultats des différentes études conduites au cours de cette thèse suggèrent que l’activité physique régulière devrait être considérée comme une pierre angulaire dans la prévention et dans la prise en charge des formes légères et modérées. De futurs études devraient être conduites afin d’explorer plus en détail les mécanismes physiologiques sous-jacents et déterminer quels patients doivent bénéficier en priorité de cette alternative thérapeutique. / The main purpose of this thesis was to assess the benefit of regular physical activity on obstructive sleep apnea (OSA). A total of five studies were conducted during this thesis and will be presented during this manuscript. These studies took place in two different practice settings: a community setting within the French Federation of Physical Education and Voluntary Gymnastics (FFEPGV) and an in-hospital setting into the Cardiopulmonary Rehabilitation Unit of the University Hospital of Saint-Etienne.Our main study, EXESAS, evaluated the benefit of a community physical activity program practiced within the FFEPGV (NeuroGyV™ program) in a randomized controlled trial including 96 patients aged from 40 to 80 years with moderate OSA. We demonstrated that nine months of NeuroGyV™ program, including three hours of physical activity per week, could "cure" (apnea-hypopnea index [IAH] <15 events/hour) 58% of patients in the exercise group while only 20% of patients in the control group who received dietary advice and physical activity recommendations were considered cured. At the end of the program, patients in the exercise group also improved their quality of life and reduced their sleepiness. Beyond the improvement of the AHI, we demonstrated an increase in the maximum oxygen consumption during exercise test, suggesting a cardiovascular risk reduction.The EXESAS study also investigated the effect of the NeuroGyV™ program on autonomic nervous system (ANS) activity as measured by heart rate variability (HRV). We showed that ANS activity is preserved in OSA patients who benefited from the physical activity program. In contrast, patients in the control group had a greater hypoxemic load and decreased heart rate variability, suggesting that OSA and the associated cardiovascular risk worsened spontaneously in absence of regular physical activity.The screening of the EXESAS study led to an abstract on the choice of the most relevant OSA screening questionnaire in the general population. We showed that the STOP-BANG questionnaire had a better sensitivity than the Berlin and thus STOP-BANG questionnaire should be preferred in clinical screening even if its specificity remains low.Finally, our trial in cardiac rehabilitation confirmed the benefit of exercise training on OSA severity and on the rebalancing of ANS in coronary arterial disease (CAD) patients. Yet, preliminary results from the RICAOS study showed that inspiratory muscles training in CAD patients with moderate OSA do not provide additional benefits over a standard cardiac rehabilitation program.In conclusion, regular physical activity effectively reduces the severity of OSA in patients with or without a history of heart disease. The results of the five studies conducted during this thesis suggest that regular physical activity should be considered as a cornerstone in the prevention and management of mild and moderate forms.Future studies should be conducted to explore in more detail the underlying physiological mechanisms and determine which patients should better benefit from this therapeutic alternative as a matter of priority.

Introdução: O envelhecimento está associado com a diminuição de uma série de funções, incluindo a função pulmonar, a variabilidade da freqüência cardíaca, o barorreflexo espontâneo, a qualidade de vida e de sono, assim como com o aumento de níveis de estresse. Estudos recentes sugerem que os exercícios respiratórios do Yoga podem melhorar as funções respiratória e cardiovascular, além de aumentar a qualidade de vida e de sono e reduzir os sintomas de estresse em populações de pacientes com doença pulmonar. A hipótese testada no presente trabalho é de que o treinamento respiratório do Yoga pode melhorar a função respiratória, a variabilidade da freqüência cardíaca, a qualidade de vida e de sono e os sintomas de estresse de idosos saudáveis. Objetivo: Investigar os efeitos do treinamento de técnica respiratória do Yoga na função pulmonar, na variabilidade da freqüência cardíaca e no barorreflexo espontâneo, assim como na qualidade de vida, na qualidade de sono e nos sintomas de estresse de idosos saudáveis. Métodos: Vinte e nove voluntários idosos saudáveis (idade: 68±6 anos, homens: 34%, índice de massa corporal=25±3 kg/m2) foram aleatorizados para 4 meses de treinamento constituído por 2 aulas/semana, acrescidas de exercícios em casa 2 vezes por dia de alongamento (Controle, n=14) ou exercícios respiratórios (Yoga, n=15). Os exercícios respiratórios do Yoga (bhastrika) são constituídos de uma seqüência de exercícios que se iniciam por expirações rápidas e forçadas (kapalabhati), seguidas por inspiração pela narina direita, apnéia inspiratória com a geração de pressão negativa intratorácica e expiração pela narina esquerda (surya bedhana). Foram realizadas medidas de função pulmonar, pressões expiratória e inspiratória máximas (PEmax e PImax, respectivamente), variabilidade da freqüência cardíaca e da pressão arterial para a determinação do barorreflexo espontâneo no início do estudo (basal) e ao final, após 4 meses de treinamento (4 meses). Também foram aplicados questionários de qualidade de vida, qualidade de sono e sintomatologia de estresse no início e no final do estudo. Resultados: Os indivíduos de ambos os grupos foram semelhantes quanto aos parâmetros demográficos. As variáveis fisiológicas não se alteraram após 4 meses no grupo controle. No grupo Yoga, houve um aumento significante na PEmax (34%, p<0.0001) e na PImax (26%, p<0.0001), assim como também houve uma diminuição significante no componente de baixa freqüência (marcador da modulação simpática cardíaca) e uma diminuição significante da razão baixa freqüência/alta freqüência (marcador do equilíbrio simpatovagal) da variabilidade da freqüência cardíaca (40%, p<0.001). A sensibilidade do barorreflexo espontâneo não se alterou no grupo Yoga. Ocorreram aumentos marginais no grupo Yoga, que não atingiram significância estatística na qualidade de vida e nos sintomas de estresse. Não houve alteração da qualidade de sono. Conclusão: O treinamento respiratório do Yoga pode ser benéfico para a população idosa saudável, pois pode melhorar a fisiologia respiratória e o equilíbrio simpatovagal / Introduction: Aging is associated with a decline of many functions, including pulmonary function, heart rate variability, spontaneous baroreflex, quality of life, quality of sleep, and with the increase of stress symptoms. Recent studies suggest that Yoga respiratory exercises may improve respiratory and cardiovascular function, increase quality of life, quality of sleep and decrease stress symptoms in patients with pulmonary disease. The hypothesis tested in the present study is that Yoga respiratory training may improve respiratory function, heart rate variability, quality of life, quality of sleep and stress symptoms in healthy elderly subjects. Objective: To investigate the effects of a respiratory Yoga training on respiratory function, heart rate variability and spontaneous baroreflex, as well as on quality of life, quality of sleep and stress symptoms in healthy elderly subjects. Methods: Twenty-nine healthy elderly volunteers (age: 68±6 years, males: 34%, body mass index=25±3 kg/m2) were randomized into a 4-month training program composed of 2 classes/week plus home exercises twice a day of either stretching (Control, n=14) or respiratory exercises (Yoga, n=15). Yoga respiratory exercises (bhastrika) are composed by a sequence of exercises which begins with rapid forced expirations (kapalabhati), followed by inspiration through the right nostril, inspiratory apnoea with generation of intrathoracic negative pressure, and expiration through the left nostril (surya bedhana). Pulmonary function test, maximum expiratory and inspiratory pressures (PEmax and PImax, respectively), heart rate and blood pressure variability for spontaneous baroreflex determination were measured at baseline and after 4 months. Quality of life, quality of sleep, and stress symptoms questionnaires were also applied in the beginning and at the end of the study. Results: Subjects from both groups were similar for demographic parameters. Physiological variables did not change after 4 months in the Control group. In the Yoga group, there was a significant increase in PEmax (34%, p<0.0001) and in PImax (26%, p<0.0001), and a significant decrease in the low-frequency component (marker of cardiac sympathetic modulation) and a significant decrease in low frequency/high frequency (marker of sympathovagal balance) of heart rate variability (40%, p<0.001). Spontaneous baroreflex sensitivity did not change in the Yoga group. There were only marginal increases in quality of life, and in stress symptoms in the Yoga group, with no statistical significance, and no changes in quality of sleep. Conclusion: Respiratory Yoga training may be beneficial to the elderly healthy population, for it may improve respiratory physiology and sympathovagal balance

L'insuffisance cardiaque chronique (ICC) est une maladie dite " systémique " caractérisée notamment par le dérèglement de la balance végétative cardiaque et par un remodelage de l'architecture du tissu cardiaque. En rééducation cardiovasculaire, l'activité physique (AP) modérée et régulière joue un rôle majeur : améliorant les symptômes, la qualité de vie, l'aptitude physique des patients, elle permet de réduire les ré-hospitalisations et impacte favorablement la morbi-mortalité. Dans un premier travail bibliographique nous proposons une synthèse des effets bénéfiques de l'AP chez l'ICC, sur le rééquilibrage de l'activité orthosympathique et parasympathique. Puis, dans un deuxième travail, nous montrons que le réentraînement à l'effort par intervalles, court, intense, avec récupération passive améliore plus efficacement la capacité physique et le tonus vagal chez le patient ICC comparativement à un entraînement d'intensité modérée et continue. Enfin dans un troisième travail initié chez le rongeur en IC systolique post-ischémique, les analyses histologiques indiquent que l'entraînement débuté très tôt après la phase aigüe (J+7), provoque à la fois une hypertrophie et une amélioration de l'organisation structurelle des cardiomyocytes (alignement de l'appareil contractile, réorganisation de l'agencement des mitochondries inter-fibrillaires et des disques intercalaires). Par contre, la question de la prolifération des cardiomyocytes induite par l'entraînement reste entière pour le moment. En synthèse, notre projet Doctoral s'articule autour d'un projet clinique chez le patient ICC et d'une étude fondamentale chez la souris IC post-ischémique. L'objectif général de ces travaux est de déterminer de nouvelles caractéristiques pour les programmes d'exercice physique dans l'ICC, utilisables en pratique clinique courante au cours de la réadaptation cardiovasculaire. / Chronic heart failure (CHF) is characterized by the disruption of the cardiac vegetative balance and by a remodelling of the architecture of the cardiac tissue. Moderate and regular physical activity (PA) is the cornerstone of the cardiovascular rehabilitation programs. By improving symptoms, quality of life, physical fitness of the patients, PA also reduce re-hospitalization and had a favourable impact on morbi-mortality. In a first work, we propose a review of the beneficial effects of PA in patients with CHF, on the sympathovagal balance activity. Then, in a second work, we show that short high intensity interval training with passive recovery is more efficient than moderate intensity and continuous training to improve physical fitness and vagal tone in CHF patients. Finally, in a third work initiated in the rodent with post-ischemic heart failure, the histological analyses indicate that early (D+7, after the acute coronary syndrome) exercise training-induced both hypertrophy and an improvement of the structural organization of the cardiomyocytes. The question of exercise training-induced cardiomyocyte proliferation remains. In summary, our PhD project is based on two studies merging clinical trial and basic research. The overall goal of this work is to identify new features for physical exercise training programs in CHF that can be used in routine care during cardiovascular rehabilitation.

Orientador: Vitor Engrácia Valenti / Resumo: Os impactos do peso ao nascer (PN) em relação à variabilidade da frequência cardíaca (VFC), não estão bem esclarecidos. Objetivo: investigar o envolvimento do PN e composição corporal na recuperação da VFC após exercício físico (EF) em crianças de 9 a 11 anos (40♀ e 27♂; n=67) divididas em dois grupos: G1 (PN≤3.400g, n=33) e G2 (PN>3.400g, n=34) que completaram protocolo de EF em esteira. Nos grupos G1 e G2 a pressão arterial sistólica (PAS) e frequência respiratória (f) foram diminuídas. No grupo G2, a média da frequência cardíaca (FC), índices HF, RMSSD, SD1 e L-mean foram diminuídos e o índice L-max aumentou. Regressão linear revelou relação do percentual de gordura (%GC) e PN com recuperação não linear da VFC. Em conclusão, a recuperação autonômica após EF foi um pouco atrasada em crianças com alto PN. O PN e o %GC influenciaram levemente a recuperação da VFC. A forma como o tipo de parto poderia afetar a VFC em crianças ainda é obscura. O objetivo desta pesquisa foi investigar a recuperação autonômica do ritmo cardíaco após EF em crianças com diferentes tipos de parto. O estudo foi realizado em crianças de 9 a 11 anos (17♀ e 16♂; n=33) divididas em dois grupos: PVN (7♀ e 6♂) e PC (10♀e 10♂) que completaram protocolo de EF em esteira ergométrica. PAS, f e a média da FC foram diminuídas grupo PVN. RMSSD e os índices 2ULV e SD1 foram diminuídos no grupo PC. Em conclusão, a análise linear e não-linear da VFC mostrou que o grupo PVN apresentou tendência de recuperação autonôm... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The impacts of birth weight (BW) in relation to heart rate variability (HRV) are not well understood. Objective: To investigate the involvement of BW and body composition in HRV recovery after physical exercise (PE) in children aged 9 to 11 years (40♀ and 27♂; n = 67) divided into two groups: G1 (BW ≤3,400g, n=33) and G2 (BW >3,400g, n=34) who completed treadmill PE protocol. In groups G1 and G2, systolic blood pressure (SBP) and respiratory rate (f) were decreased. In group G2, the mean heart rate (HR), HF, RMSSD, SD1 and L-mean indices were decreased and the L-max index increased. Linear regression revealed an relationship between fat percentage (%FP) and BW with nonlinear HRV recovery. In conclusion, autonomic recovery after PE was a little late in children with high BW. BW and %FP slightly influenced HRV recovery. How childbirth could affect HRV in children is still unclear. The aim of this research was to investigate the autonomic recovery of heart rate after PE in children with different types of delivery. The study was conducted in children aged 9 to 11 years (17♀ and 16♂; n=33) divided into two groups: PVN (7♀ and 6♂) and PC (10♀ and 10♂) who completed PE protocol in treadmill. SBP, f and mean HR were decreased in PVN group. RMSSD and 2ULV and SD1 indices were decreased in the PC group. In conclusion, the linear and nonlinear HRV analysis showed that the PVN group showed a tendency for faster autonomic and cardiovascular recovery after PE. / Doutor