Made available in DSpace on 2016-06-02T20:18:23Z (GMT). No. of bitstreams: 1 6236.pdf: 2944020 bytes, checksum: dcbf2b2eaca77c3425524a77887f4d6b (MD5) Previous issue date: 2014-06-06 / Universidade Federal de Minas Gerais / The aging process affects many systems of the human body, including: autonomic nervous system, which can be assessed by heart rate variability (HRV); cellular structures, such as telomere length; and mechanisms of regulation of the inflammatory process, which can be evaluated by inflammatory markers such as high-sensitivity C-reactive protein (hsCRP). The combined analysis of these variables enables the study of the aging process in a multidimensional way. Additionally, the effects of hormone replacement therapy (HRT) on HRV are contradictory. In this way, we conducted the study I, which aimed to investigate the effects of HRT on HRV in healthy postmenopausal women. Two groups were evaluated: Group 1 (G1): 20 women who did not use HRT (60 ± 5.89 years) and group 2 (G2): 20 women undergoing HRT (59 ± 5.70 years). The electrocardiogram was recorded in supine position for 10 min. Spectral analysis included low and high frequency in absolute (LF and HF) and normalized (LFnu and HFnu) units. LF/HF ratio was also calculated. Symbolic analysis (0V%, 1V%, 2LV% e 2UV%), Shannon and conditional entropy were calculated. LF, LFnu and LF/HF ratio were higher, whereas HFnu was lower in G2 than in G1. Correlations between complexity indices and HFnu were significant and positive only in G1. We conclude that women undergoing HRT had higher cardiac sympathetic modulation and reduced cardiac vagal modulation compared to women not using HRT. Moreover, the expected positive relationship between cardiac vagal modulation and HRV complexity was found only in the group not undergoing HRT, indicating that vagal modulation in women under therapy drop below a minimum value necessary to the association to become apparent, suggesting an unfavorable cardiac autonomic modulation in spite of HRT. Considering the findings of the study I, we chose to adopt the use of the therapy as an exclusion criterion for the study II. Thus, the study II aimed to examine the aging effect on heart rate variability in supine and standing, on serum hsCRP and leukocyte telomere length, as well as to verify the age at which the changes caused by aging process are accentuated. One hundred and ten volunteers were divided into five groups according to age: G21-30 years, G31-40 years, G41-50 years, G51-60 years, and G61-70 years. Venous blood samples were collected for measurements of serum hsCRP and telomere length. ECG signals were recorded in rest supine and standing (15 min in each posture). HRV was assessed by spectral analysis in low and high frequencies in absolute (LF e HF) and normalized (LFnu e HFnu) units; symbolic analysis (0V%, 1V%, 2LV% e 2UV%); Shannon entropy; and complexity index (CI) and normalized CI (NCI) from conditional entropy. The main results were: 1) HF and 2UV% reduction (vagal modulation) in G51-60, and 0V% increase (sympathetic modulation) and NCI reduction (complexity) in G61-70, in supine; 2) less efficient response to postural change from supine to standing with advancing age; 3) hsCRP increase in G51-60; 4) telomere shortening in G61-70; 5) in supine, HRV indices showed stronger relationship with the principal component of most relevance from the multivariate principal component analysis, compared to hsCRP and telomere length. Considering that HRV indices in supine had a stronger association with the aging process, we can conclude that the decrease in cardiac vagal modulation may have influenced the increase in serum hsCRP (although normal values), in G51-60, since this effect is described by the cholinergic anti-inflammatory pathway. Decreased cardiac vagal modulation and increased hsCRP may have contributed to the telomere shortening identified in the following decade (G61-70). In this way, we must consider the importance of preventive actions prior to the onset of aging effects, particularly in the 41-50 age range, in an attempt to attenuate the natural effects of senescence. / O envelhecimento exerce influência sobre vários sistemas do corpo humano, dentre eles: sistema nervoso autonômico, que pode ser avaliado pela variabilidade da frequência cardíaca (VFC); estruturas celulares, como o comprimento de telômeros; e mecanismos reguladores de processos inflamatórios, que podem ser avaliados por marcadores inflamatórios, como a proteína C-reativa ultra sensível (PCRus). A análise conjunta dessas variáveis permitiria o estudo do processo de envelhecimento de forma multidimensional. Adicionalmente, são controversos os efeitos da terapia de reposição hormonal (TRH) sobre a VFC. Assim, foi realizado o estudo I, o qual teve por objetivo investigar os efeitos da TRH na VFC em mulheres pós-menopáusicas saudáveis. Foram avaliados dois grupos: grupo 1 (G1): 20 mulheres que não faziam uso de TRH (60 ± 5,89 anos) e grupo 2 (G2): 20 mulheres submetidas à TRH (59 ± 5,70 anos). O eletrocardiograma foi registrado na posição supina por 10 min. A análise espectral incluiu a baixa e a alta frequência em unidades absolutas (BF e AF) e normalizadas (BFun e AFun). A relação BF/AF também foi calculada. A análise simbólica (0V%, 1V%, 2LV% e 2UV%), e entropias de Shannon e condicional também foram calculadas. BF, BFun e a razão BF/AF foram maiores, enquanto AFun foi menor no G2 do que no G1. As correlações entre índices de complexidade e AFun foram significativos e positivos apenas no G1. Concluímos que mulheres submetidas à TRH apresentaram maior modulação cardíaca simpática e menor modulação cardíaca vagal em comparação às que não faziam a terapia. Além disso, a relação positiva esperada entre modulação cardíaca vagal e a complexidade da VFC foi encontrada apenas no grupo não submetido à TRH, indicando que a modulação vagal em mulheres sob a terapia não atinge um valor mínimo necessário para a associação se tornar aparente, sugerindo uma modulação autonômica cardíaca desfavorável, apesar da TRH. A partir dos achados do estudo I, optou-se por adotar, como critério de exclusão para o estudo II, o uso da terapia. Assim, o estudo II teve por objetivo analisar o efeito do envelhecimento sobre a VFC nas posições supina e ortostática, os níveis séricos da PCRus e o comprimento de telômeros leucocitários, além de verificar em qual faixa etária se acentuam as alterações provocadas pelo processo de envelhecimento. Foram avaliados 110 voluntários, divididos em cinco grupos, de acordo com a idade: G21-30 anos, G31-40 anos, G41-50 anos, G51-60 anos e G61-70 anos. Amostras de sangue venoso foram coletadas para medidas de PCRus e comprimento de telômeros. Os sinais eletrocardiográficos foram registrados em repouso nas posições supina e ortostática (15 min em cada postura). A VFC foi avaliada por índices de baixa e alta frequências em unidades absolutas (BF e AF) e normalizadas (BFun e AFun) da análise espectral; índices 0V%, 1V%, 2LV% e 2UV% da análise simbólica; entropia de Shannon; e índice de complexidade (IC) e IC normalizado (ICN) da entropia condicional. Os principais resultados foram: 1) redução de AF e 2UV% (modulação vagal) em G51-60, além de aumento de 0V% (modulação simpática) e diminuição de ICN (complexidade) em G61-70 na posição supina; 2) resposta menos eficiente à manobra de mudança postural de supino para ortostatismo com o avanço da idade; 3) aumento da PCRus em G51-60; 4) encurtamento do comprimento de telômeros em G61-70; 5) na posição supina, os índices da VFC apresentaram relação mais alta com o componente principal de maior relevância, proveniente da análise multivariada por componentes principais, em comparação à PCRus e ao comprimento de telômeros. Considerando-se que os índices da VFC na posição supina apresentaram uma associação mais forte com o envelhecimento, podemos concluir que a diminuição da modulação cardíaca vagal possa ter contribuído para o aumento dos níveis séricos de PCRus (apesar dos valores estarem dentro de faixa de normalidade), na faixa etária de 51 a 60 anos, uma vez que este efeito é descrito pela via anti-inflamatória colinérgica. A diminuição da modulação cardíaca vagal e o aumento da PCRus podem ter contribuído para o encurtamento de telômeros, identificado na década seguinte, de 61 a 70 anos. Dessa maneira, torna-se importante a proposição de ações preventivas em faixas etárias anteriores ao início das alterações provocadas pelo envelhecimento, especialmente na década de 41 a 50 anos, na tentativa de atenuar os efeitos naturais da senescência.

A hipertensão arterial (HA) é uma doença multifatorial na qual há a interação de vários mecanismos, e está relacionada com alterações funcionais e/ou estruturais dos órgãos-alvo. Alterações funcionais dos mecanismos regulatórios da pressão arterial (PA) a curto prazo, como os barorreceptores e os quimiorreceptores, vem sendo bastante exploradas com o objetivo de entender os possíveis mecanismos que podem estar relacionadas à gênese da HA. Diante disso, utilizamos o modelo experimental de desnervação sinoaórtica (DSA) e desnervação seletiva desses aferentes (aórtica DA) e/ou carotídea (DC) e a ligadura da artéria do corpúsculo carotídeo (LA) para avaliarmos a importância relativa dos barorreceptores e quimioreceptores no controle neurogênico da circulação mediando respostas cardíacas e músculo-esqueléticas na HA. Para tanto, utilizamos ratos Wistar (CTR) e espontaneamente hipertensos (SHR) submetidos às diferentes desnervações (SHRDSA/ SHRDA / SHRDC), bem como, a ligadura da artéria do corpúsculo carotídeo (SHRLA). Os animais foram acompanhados durante 10 semanas após as desnervações seletivas, e em seguida foram realizadas as avaliações ecocardiográficas, gasometria arterial, hemodinâmicas, autonômicas e de fluxo sanguíneo regional. Posteriormente, os animais foram eutanasiados para a coleta dos tecidos para as avaliações gênicas e histológicas. Resultados: Os animais SHR apresentaram disfunções hemodinâmicas, autonômicas e gasométricas (alcalose respiratória) quando comparado ao grupo CTR, assim como nas análises de hipertrofia, fluxo e histologia do músculo esquelético, como transição no fenótipo para um perfil mais glicolítico no sóleo e aumento da área de secção transversa das fibras do tipo I e redução das fibras do tipo IIB no músculo diafragma. Nos grupos experimentais hipertensos, os animais com prejuízo do quimiorreflexo (SHRDC, SHRLA e SHRDSA), apresentaram valores maiores de pCO2 em relação ao grupo SHR e SHRDA. Todos os grupos com as diferentes desnervações apresentaram alterações autonômicas, de fluxo sanguíneo e de capilarização. Entretanto, nossos maiores achados foram em relação ao grupo SHRDA, que apresentou valores significativamente maiores que o grupo SHR nos parâmetros PAS (212±2 vs 200±3), PAD (156±4 vs 144±3) PAM (185±9 vs 172±3) e FC (377±4 vs 350±7). Além disso, apresentou aumento da variabilidade da PA (VPAS), bem como o simpático periférico (BFPAS), contrariamente ao observado nos grupos SHRDC e SHRLA em relação ao grupo SHR. No controle autonômico da FC, o grupo SHRDA apresentou menor efeito parassimpático e maior efeito simpático em relação ao grupo SHR. Já os grupos SHRDC e SHRLA apresentaram um menor efeito parassimpático, sem alterações no efeito simpático, embora a resistência vascular periférica estivesse aumentada no grupo SHRLA. As adaptações morfofuncionais cardíacas (ecocardiografia e marcadores de hipertrofia cardíaca) foram mais evidentes no grupo que apresentava disfunção total de ambos receptores (SHRDSA). Conclusão: A ausência do controle reflexo exercido predominantemente pelos barorreceptores arteriais demonstrou uma maior influência do componente aórtico do que o carotídeo sobre a PA. Em adição, a função sistólica parece maior nos grupos SHRDA e SHRDSA, sugerindo que a desnervação aórtica esteja associada com ativação simpática. Não se observou alteração cardíaca na desnervação carotídea. Em relação ao músculo esquelético, todas as desnervações mostraram aumento de capilarização, enquanto somente o grupo SHRDSA mostrou redução de fibras intermediárias. O aumento de capilarização pode estar associado com a liberação do simpático periférico nas desnervações que incluem a retirada dos barorreceptores aórticos, levando ao aumento de VPA e à ausência dos quimiorreceptores nos grupos com desaferentação dos receptores carotídeos / Arterial hypertension (AH) is a multifactorial disease on which there is the interaction of several mechanisms , therefore is related to functional and / or structural changes of the target organ . Functional changes of the regulatory mechanisms of blood pressure (BP) in the short term , as pressoreceptor and chemoreceptors, has been extensively explored in order to understand the possible mechanisms that may be related to the genesis of hypertension. Thus, we used the experimental model of sinoaortic denervation (DSA) and selective denervation of those afferent aortic (DA) and / or carotid (DC) and the ligature of the carotid body artery (LA) to evaluate the relative importance of baroreceptors and chemoreceptors on control of neurogenic circulation mediating cardiac and musculoskeletal responses in HA. There by, we used Wistar rats (CTR) and spontaneously hypertensive rats (SHR) subjected to different denervation (SHRDSA / SHRDA / SHRDC) and the ligature of the carotid body artery (SHRLA). The animals were followed for 10 weeks after the selective denervation it was performed echocardiographic evaluations, blood gas, hemodynamic, autonomic and regional blood flow. Subsequently, the animals were euthanized for tissue collection for genetic and histological evaluations. Results: SHR animals showed hemodynamic, autonomic dysfunction and gas exchange (respiratory alkalosis) compared to CTR group as well as the analysis of hypertrophy, flow and histology of skeletal muscle, such as the transition to a more glycolytic phenotype profile in soleus and increased cross-sectional area of type I fibers and reduction of type IIB fibers in the diaphragm . In hypertensive experimental groups, animals with prejudice chemoreflex (SHRDC, SHRLA and SHRDSA) , showed higher pCO2 compared to SHR and SHRDA group. All groups with different denervation showed autonomic changes in blood flow and capillarization. However, our major findings were compared to SHRDA group, which was significantly higher than the SHR in SBP (212 ± 2 vs 200 ± 3), DBP (156 ± 4 vs 144 ± 3), MAP (185 ± 9 vs 172 ± 3) and HR (377 ± 4 vs 350 ± 7) parameters. Furthermore, we showed an increase in BP variability (BPV) and in the peripheral sympathetic (BFPAS), otherwise showed in the groups SHRDC and SHRLA compared to SHR . Autonomic control of HR, the SHRDA group showed lower sympathetic and higher parasympathetic effect effect in relation to SHR. Already SHRDC and SHRLA groups had a lower parasympathetic effect without changes in sympathetic, although peripheral vascular resistance was increased in SHRLA group. The cardiac morphofunctional adaptations (echocardiography and cardiac hypertrophy markers) were more evident in the group that had total dysfunction of both receptors (SHRDSA). Conclusion: The absence of reflex control exerted by arterial baroreceptors predominantly showed a greater influence of the aortic component of the carotid on BP. In addition, systolic function appears higher in groups SHRDA and SHRDSA, suggesting that aortic denervation is associated with sympathetic activation. No cardiac abnormality was observed in the carotid denervation. Regarding skeletal muscle, all denervations showed an increased of capillarization, while only SHRDSA group showed reduction of intermediate fibers. Increased capillarization may be associated with the release of the peripheral sympathetic denervation, including removal of the aortic baroreceptors, leading to increased VPA and the absence of chemoreceptors in groups with deafferentation of the carotid receptors

Estudou-se o efeito do treinamento físico sobre a freqüência cardíaca (FC), a freqüência cardíaca intrínseca (FCI), o efeito vagal (EV), o tônus vagal (TV), o efeito simpático (ES) e o tônus simpático (TS), de ratos idosos em repouso volitivo, na esteira, e durante o exercício de intensidade progressiva (4 estágios de 5 min à 5; 7,5; 10 e 15 m.min-1). Verificaram-se, também, as respostas da FC à doses crescentes de agonistas ?-adrenérgico (isoproterenol) e muscarínico (metacolina). Utilizaram-se 20 ratos Wistar machos, aleatoriamente divididos em dois grupos: Treinado (T, 28+2 meses, 460+36 g), submetido a 10 semanas de treinamento físico de moderada intensidade; e Sedentário-controle (S, 28+2 meses, 461+43 g), apenas manipulado, três a cinco vezes por semana, durante nove semanas, e submetido a cinco minutos de exercício diário, na décima semana, para habituação ao pesquisador e ao ambiente experimental. Utilizaram-se duplos bloqueios farmacológicos (propranolol/atropina e atropina/propranolol) para determinação da FCI, bem como bloqueios farmacológicos autonômicos unilaterais que permitiram a medida do EV, do TV, do ES e do TS. Definições: EV = FC após atropina - FC controle, ES = FC controle - FC após propranolol, TV = FCI - FC após propranolol, TS = FC após atropina - FCI. Registros: batimento-a-batimento, 500Hz (AT/CODAS). Para comparação realizou-se análise de variância de dois caminhos para medidas repetidas, com contraste. Significância estatística, P<0,05. FC e FCI foram menores em T que S, em repouso e nos quatro estágios estudados: FC = 296+6, T vs. 325+16, S; 374+33, T vs. 420+29, S; 380+ 39, T vs. 423+29, S; 407+46, T vs. 434+25, S; 441+48, T vs. 455+30, S; e FCI = 288+28, T vs. 312+18, S; 302+27, T vs. 332+24, S; 301+30, T vs. 339+26, S; 308+30, T vs. 344+30, S; 316+31, T vs. 348+31, S. Não houve diferença na atividade vagal entre T e S, tanto considerando o EV, como o TV, em nenhuma das condições estudadas. A influência simpática para o coração se mostrou semelhante entre T e S, tanto se considerando o ES quanto o TS, em todas as condições estudadas. T e S responderam de forma semelhante aos agonistas muscarínico e adrenérgico. Tanto a FC, quanto a FCI aumentaram do repouso para o exercício, e com o aumento da intensidade do mesmo. A atividade vagal diminuiu do repouso para o exercício, mas apenas em intensidade elevada. A atividade simpática aumentou na passagem do repouso para o exercício, e com o aumento da intensidade do mesmo. Concluiu-se que, em ratos idosos: a) o treinamento físico de moderada intensidade promoveu bradicardia de repouso e atenuação da taquicardia induzida pelo exercício essencialmente à custa de redução da FCI; e b) independentemente da condição de treinamento físico, a estimulação simpática contribuiu para o aumento da FC, em resposta ao exercício, de leve à alta intensidade, enquanto a retirada vagal o fez, apenas em alta intensidade. / We studied the effect of exercise training on heart rate (HR), on intrinsic heart rate (IHR), on vagal effect (VE), on vagal tone (VT), on sympathetic effect (SE) and on sympathetic tone (ST) during both treadmill resting and exercise of progressive intensity (four 5-min stages at 5, 7.5, 10 and 15 m.min-1) in old rats. HR responses to crescent doses of ?-adrenergic (isoproterenol) and muscarinic (metacholine) agonists were also verified. We used 20 male Wistar rats randomly assigned to two groups: trained (T, 28+2 months, 460+36 g) and sedentary control (S, 28+2 months, 461+43 g) rats. T was submitted to a ten-week moderate intensity exercise training program, while S was just handled, three to five times a week, for nine weeks and submitted to five-min bouts of daily exercise during the tenth week for taming and to become accustomed to experimental environment. Double pharmacological blockades (propranolol/ methylatropine and methylatropine/propranolol) were performed in order to determine IHR. Autonomic influences on heart rate were evaluated using also unilateral autonomic pharmacological blockade, which allowed us to measure VE and VT as well as SE and ST. Definitions: VE = HR after atropine - control HR, SE = control HR - HR after propranolol, VT = IHR - HR after propranolol, ST = HR after atropine - IHR. HR was recorded on a beat-to-beat basis with a 500 Hz acquisition frequency (AT/CODAS). For statistical analysis we used two-way ANOVA for repeated measurements with contrast, considering a P<0.05 as statistically significant. T rats had lower HR as well as IHR than their sedentary counterparts both at rest and during all progressive exercise stages: HR = 296+6,T vs. 325+16,S; 374+33,T vs. 420+29,S; 380+39,T vs. 423+29,S; 407+46,T vs. 434+25,S; 441+48,T vs. 455+30,S, respectively; and IHR = 288+28,T vs. 312+18,S; 302+27,T vs. 332+24,S; 301+30,T vs. 339+26,S; 308+30,T vs. 344+30,S; 316+31,T vs. 348+31,S, respectively. Vagal activity was not significantly different between groups, either considering VE or VT. Sympathetic influence was also similar between S and T considering both SE and ST in all of the studied conditions. T and S responded similarly to both muscarinic and ?-adrenergic agonists. Both HR and IHR increased from rest to exercise and with increasing exercise intensity. Vagal activity decreased from rest to exercise but only in high intensity exercise. Sympathetic activity increased from rest to exercise and also with increasing exercise intensity. We concluded that in old rats: a) exercise training of moderate intensity led to resting bradycardia and attenuation of exercise tachycardia essentially due to the decrease in IHR; and b) independently from exercise training status, sympathetic stimulation contributed to HR increase from light to high intensity exercise while vagal withdrawal became important only at high intensity exercise

Alterações metabólicas, inflamatórias e do sistema nervoso autônomo estão presentes em pacientes com insuficiência cardíaca. No entanto, não há até o momento, consenso de que tais alterações são decorrentes da disfunção ventricular ou da síndrome de insuficiência cardíaca. Objetivo: Avaliacão do metabolismo e atividade inflamatória em pacientes com miocardiopatia dilatada chagásica e idiopática e sua correlação com medidas de funcão do sistema nervoso autônomo. Casuística: Foram avaliados 46 pacientes divididos em três grupos: pacientes com miocardiopatia dilatada idiopática, chagásica e controle, pareados entre si de acordo com sexo e idade e índice de massa corpórea. Critérios de inclusão: miocardiopatia chagásica com sorologia positiva em dois métodos diferentes (imunofluorescência indireta e ELISA) e miocardiopatia dilatada idiopática com idade superior a 18 anos; ambos os sexos; Índice de massa corporal (IMC) entre 18,5 e 25 kg/m2 e fração de ejeção < 40% pelo método de Simpson ao ecocardiograma. Metodologia: Todos pacientes foram submetidos a medidas antropométricas: índice de massa corporal e medida da porcentagem de gordura corporal através de bioimpedância. Coletado sangue para dosagens sanguíneas de leptina, adiponectina, interleucina-6, fator de necrose tumoral, glicose, insulina, colesterol total, HDL-Colesterol, LDL-Colesterol e triglicerídeos após jejum de 12 horas e realizados: Holter de 24 horas para avaliação da função autonômica, ecocardiograma transtorácico bidimensional complementado com modo-M, Doppler pulsátil, tecidual e colorido. Resultados: Não houve diferenças entre os grupos com relação a dosagem de glicemia, colesterol total, LDL-colesterol, HDL-colesterol e triglicerídeos. Com relação à leptina e adiponectina e o índice HOMA-IR, não houve diferença entre os grupos. As dosagens de insulina foram menores no grupo chagásico em comparação ao grupo controle e de idiopático (5,4; 8,0; 9,9) respectivamente (p = 0,007). As dosagens de interleucina-6 e fator de necrose tumoral-alfa foram maiores no grupo chagásico em relação aos outros grupos. A insulina correlacionou positivamente no grupo chagásico com leptina (r = 0,579; p = 0,024) e sistema nervoso autônomo ( atividade simpática) BF/AF ( r = 0,562; p = 0,029) e BF (r = 0,562; p = 0,029) e negativamente com adiponectina (r = -0,603; p = 0,017). Na análise multivariada, apenas a adiponectina foi significante. A adição de uma unidade de adiponectina reduziu a média de insulina em 0,332. Conclusões: Os níveis de insulina foram menores nos pacientes com miocardiopatia chagásica em comparação aos pacientes com miocardiopatia dilatada idiopática e controle. Os níveis das citocinas inflamatórias (TNF-alfa e interleucina-6) foram maiores nos pacientes com miocardiopatia chagásica em comparação aos pacientes com miocardiopatia dilatada idiopática e controle. A insulina correlacionou negativamente no grupo chagásico com adiponectina / Metabolic, inflammatory and autonomic nervous system changes are present in patients with heart failure. However, there is so far, consensus that these changes are due to ventricular dysfunction or heart failure syndrome. Objective: Evaluation of metabolism and inflammatory activity in patients with Chagas\' disease and idiopathic dilated cardiomyopathy and its correlation with user function measures the autonomic nervous system. Patients: A total of 46 patients divided into three groups: patients with idiopathic dilated cardiomyopathy, Chagas and control, matched each other according to sex and age and body mass index. Inclusion criteria: serology for Chagas\' disease in two different methods (indirect immunofluorescence and ELISA); idiopathic dilated cardiomyopathy; older than 18 years; both sexes; Body mass index (BMI), ie between 18.5 and 25 kg / m2 and ejection fraction < 40% by Simpson method by echocardiography. Methods: All patients underwent anthropometric measurements: body mass index and measure the percentage of body fat by bioimpedance. Blood was collected for blood leptin dosages, adiponectin, interleukin-6, tumor necrosis factor, glucose, insulin, total cholesterol, HDLcholesterol, LDL-cholesterol and triglyceride levels after fasting for 12 hours and performed: 24 hours for evaluation Holter autonomic function, two-dimensional transthoracic echocardiography complemented by M-mode, pulsed Doppler, tissue and colorful. Results: There were no differences between groups with respect to blood glucose levels, total cholesterol, LDL-cholesterol, HDLcholesterol and triglycerides. With respect to leptin and adiponectin and HOMAIR, there was no difference between groups. Insulin doses were lower in the chagasic group compared to the control group and Idiopathic: 5.4; 8.0; 9.9, respectively (p = 0.007). Dosages of interleukin-6 and tumor necrosis factoralpha were higher in the chagasic group compared to other groups. Insulin positively correlated in the chagasic group with leptin (r = 0.579; p = 0.024) and autonomic nervous system (sympathetic activity) LF / HF (r = 0.562; p = 0.029) and BF (r = 0.562; p = 0.029) and negatively with adiponectin (r = -0.603; p = 0.017). In multivariate analysis, only adiponectin was significant. The addition of an adiponectin unit reduced the average insulin 0.332. Conclusions: Insulin levels were lower in patients with Chagas\' heart disease compared to patients with idiopathic dilated cardiomyopathy and control. The levels of inflammatory cytokines (TNF-alpha and interleukin-6) were higher in patients with Chagas\' heart disease compared to patients with idiopathic dilated cardiomyopathy and control. Insulin negatively correlated with adiponectin in the chagasic group

<p>Izvod: UVOD: Metabolički zdrave gojazne osobe su okarakterisane odsustvom metaboličkog sindroma i/ili insulinske rezistencije i sistemske inflamacije. Mali je broj podataka o ulozi aktivnosti autonomnog nervnog sistema u razvoju kardiometaboličkih komplikacija kod gojaznih osoba, kao i o njegovoj vezi sa specifičnom distribucijom masnog tkiva. CILJ: Analiza varijabilnost srčane frekvencije (HRV) kod metabolički zdravih (MHO) i gojaznih osoba sa metaboličkim rizikom (MUO), analiza povezanosti HRV sa metaboličkim faktorima i distribucijom masnog tkiva, kao i analiza uzrasne dinamike HRV kod gojaznih osoba različitih kardiometaboličkih profila. MATERIJAL I METODE: Ukupno 125 gojaznih ispitanika oba pola podvrgnuto je antropometrijskim merenjima u cilju procene mase i distribucije masnog tkiva, izvr&scaron;ena je analiza telesne kompozicije, uzeti su uzorci krvi u cilju određivanja lipidskog i lipoproteinskog statusa, stanja glikoregulacije i nivoa inflamatornih markera, meren je krvni pritisak i procenjena je HRV tokom petominutne digitalne elektrokardiografije. Podaci su statistički obrađeni kori&scaron;ćenjem paketa SPSS 11.5. REZULTATI: HRV mere se nisu razlikovale statistički značajno među MHO i MUO mu&scaron;karcima. MHO žene su imale vi&scaron;e vrednosti RRNN, SDNN, RMSSD, pNN50, LF, HF i TP u odnosu na MUO žene, na čega metabolički profil utiče sa 6,6-11,2%(p˂0,01), predstavljeno kroz parcijalnu deljenu varijansu. Nakon antropometrijskih faktora uzetih u obzir, perzistirale su vi&scaron;e vrednosti HF kod MHO žena. Razlika u RRNN, pNN50 i TP između MHO i MUO premenopauzalnih žena (vi&scaron;e vrednosti za MHO, p˂0,05) se izgubila nakon kontrole za krvni pritisak. Insulinemija je uticala na pojave razlika u RRNN između MHO i MUO premenopauzalnih žena, parcijalna deljena varijansa 7,6%. SAD kod žena se negativno povezivao sa LF/HF i LFnorm, a pozitivno sa HFnorm, parcijalne deljene varijanse 8,4-11,9% (p˂0,05). Prednji nabor podlaktice kod žena se pozitivno povezivao sa LF i LF/HF, a negativno sa HFnorm (p˂0,01). Visceralna masna masa je predviđala značajno HRV mere mu&scaron;karaca, parcijalna deljena varijansa 13-34% (p˂0,01). U okviru gornjeg tercila HRV mera RMSSD, pNN50 i LF MUO osoba, HOMA indeks je statistički značajno niži (p˂0,05). Kod MUO osoba SDNN, RMSSD, lnpNN50, lnLF, lnHF i TP značajno su se smanjivali u uzrastu od 19-29 do 40-49 godina. Kod MHO osoba primetna je uzrasna promena HF mere u četvrtoj deceniji života. ZAKLJUČAK: MHO osobe ženskog pola imaju značajno vi&scaron;e vrednosti markera varijabilnosti srčane frekvencije u odnosu na MUO. Razlike u HRV merama su uslovljene kriterijumima metaboličke podele, predominantno insulinemijom, vrednostima krvnog pritiska i centralnom masnom masom. Kod žena centralna distribucija masnog tkiva korelira sa smanjenom srčanom simpatičkom aktivno&scaron;ću dok se periferna distribucija masnog tkiva povezuje obrnuto sa komponentama aktivnosti autonomnog nervnog sistema. Kod mu&scaron;karaca centralna masna masa, ali ne i periferna, je značajno povezana sa HRV. MUO osobe sa nižom HRV imaju veći stepen insulinske rezistencije, dok HRV ne utiče na insulinsku senzitivnost MHO osoba. Značajniji uzrasno zavisni pad HRV mera primetan je kod MUO osoba, pogađajući obe komponente autonomnog nervnog sistema za razliku od MHO osoba.</p> / <p>Abstract: INTRODUCTION: Metabolically healthy obese (MHO) individuals are characterized by absence of metabolic syndrome and/or insulin resistance and inflammation. Little is known about the role of autonomic nervous system in development of cardiometabolic complications in obese people and about its influence on the specific adipose tissue distribution. AIM: Analysis of the hearth rate variability (HRV) in metabolically healthy (MHO) and unhealthy (MUO) obese people, its connection with adipose tissue distribution, and age dependent dynamics of HRV. MATERIAL AND METHODS: A total of 125 obese patients of both sexes underwent anthropometric measurements in order to assess adipose tissue mass and distribution, body composition was assessed, blood samples were taken in order to analyze parameters of lipid and lipoprotein profile, condition of glycoregulation and inflammatory markers, blood pressure was measured and short term HRV was conducted. Data were statisticaly analyzed using SPSS 11.5. RESULTS: HRV measures did not differ significantly between MHO and MUO men. MHO women had higher values of RRNN, SDNN, RMSSD, pNN50, LF, HF and TP compared to the MUO women, influence of metabolic profile was 6,6-11,2% (p˂0,01), presented through partial shared variance. After controlling for anthropometric factors higher HF persisted in MHO women. Differences in RRNN, pNN50 and TP between MHO and MUO premenopausal women (higher values of MHO, p˂0,05) were lost after controlling for blood pressure. Insulinemia influenced the difference in RRNN between MHO and MUO premenopausal women, partial shared variance 7,6%. SAD in women was connected negatively with the LF/HF and LFnorm, and positively with HFnorm, partial shared variance 8,4-11,9% (p˂0,05). Anterior forearm skinfold in women correlated positively with LF and LF/HF, and negatively with HFnorm (p˂0,01). Visceral fat mass predicted significantly HRV in men, partial shared variance 13-34% (p˂0,01). Within the upper tertile of HRV measures RMSSD, pNN50 and LF in MUO people, HOMA was significantly lower (p˂0,05). In MUO SDNN, RMSSD, lnpNN50, lnLF,lnHF and TP significantly decreased in the period from 19-29 to 40-49 years. In MHO people the change in HF was noticeable in the fourth decade of life. CONCLUSION: MHO women have significantly higher levels of HRV markers comparing to the MUO. The differences in HRV measures are influenced by metabolic criteria used, predominantly by insulinemia, blood pressure and central fat mass. In women, central distribution of adipose tissue correlates with reduced cardiac sympathetic activity, while the connection of peripheral fat mass distribution with components of autonomic nervuos system activity is reverse. In men, central fat mass, but not peripheral, is significantly associated with HRV. MUO people with lower HRV have a higher degree of insulin resistance, while the level of HRV measures does not affect insulin sensitivity in MHO individuals. Significant age-dependent decrease in both ANS representatives of HRV measures was noticed in MUO people, unlike MHO individuals.</p>

Background: Work-related stress (WRS) is associated with musculoskeletal pain (MSP), changes in the autonomic nervous system (ANS) and anxiety. Objective: To determine the feasibility of a follow-up study and treatment efficacy of the Reaset Approach on MSP, ANS and State-Trait anxiety. Methods: 15 subjects with WRS and MSP were assigned into 3 groups (Body, Head-Neck, Head-Neck-Body). Each group received a single 25 minute ‘Reaset Approach’ intervention. Heart rate variability (HRV), electro-dermal activity (EDA), State Trait Anxiety (STAI) and MSP were measured. Results: HRV parameters: SDNN increased in 13 of 15 subjects while SD1 and SD2 increased in 12 of 15 subjects. EDA reduced in 10 of 14 subjects. State Anxiety reduced in all subjects and Trait Anxiety reduced in 14 of 15 subjects. MSP reduced in all subjects after the intervention and were still lower three days afterwards. Conclusions: This pilot study determined that a follow-up study can ensue provided minor modifications are implemented and that the ‘Reaset Approach’ has an influence on the ANS, anxiety and MSP. Results do differ between groups. The intervention groups including the head and neck modalities demonstrated better results.:I. Abstract (En) III II. Abstract (De) IV III. Table of Contents V IV. Index of figures VIII V. Index of tables IX VI. Index of abbreviations X 1 Introduction 1 2 Background 2 2.1 Work-related musculoskeletal pain 2 2.2 Work-related stress 3 2.3 Osteopathy and the autonomic nervous system 3 2.4 Stress, pain and osteopathy 4 3 Questions 6 3.1 Feasibility 6 3.2 Treatment effect 6 4 Methods 7 4.1 Study design 7 4.2 Participants 8 4.2.1 Inclusion criteria 8 4.2.2 Exclusion criteria 8 4.2.3 Recruitment 8 4.2.4 Randomization 10 4.3 Parameters 11 4.3.1 Heart rate variability 11 4.3.2 Electro-dermal activity 11 4.3.3 State anxiety 11 4.3.4 Trait anxiety 12 4.3.5 Perceived pain 12 4.4 Measuring Instruments 13 4.4.1 Heart rate variability 13 4.4.2 Electro-dermal Activity 13 4.4.3 State-Trait Anxiety Inventory 13 4.4.4 Short-Form McGill Pain Questionnaire 13 4.5 Interventions 14 4.5.1 Intervention ‘B’: Body 14 4.5.2 Intervention ‘HN’: Head and Neck 16 4.5.3 Intervention ‘HNB’: Head, Neck and Body 16 4.6 Study flow 18 4.7 Statistics 20 5 Results 21 5.1 Autonomic nervous system: Heart rate variability 21 5.1.1 SDNN 22 5.1.2 SD1 25 5.1.3 SD2 28 5.2 Autonomic Nervous System: Electro-dermal activity 31 5.3 Anxiety 34 5.3.1 State anxiety 34 5.3.2 Trait anxiety 37 5.4 Musculoskeletal pain 39 5.4.1 Visual analogue scale 40 5.4.2 Total Short-Form McGill Pain Questionnaire 43 6 Discussion 46 6.1 Discussion of the method 46 6.2 Discussion of the results 50 6.2.1 Autonomic nervous system 50 6.2.1.1 Heart rate variability 50 6.2.1.2 Electro-dermal activity 51 6.2.2 Anxiety 51 6.2.2.1 State anxiety 51 6.2.2.2 Trait Anxiety 52 6.2.3 Musculoskeletal pain 52 6.3 Suggestions for future research 53 7 Conclusion 54 8 Literature 55 9 Addendum 63 9.1 Table: SF-MPQ with Sensory, Affective and Evaluative dimension 63 9.2 Patient Information Sheet 64 9.3 Structured telephone interview 70 9.4 Structured pre-treatment interview 72 9.5 SF-MPQ permission 73 9.6 SF-MPQ 74 9.7 STAI License 76 9.8 STAI forms Y-1 and Y-2 77 / Hintergrund: Arbeitsbedingter Stress (ABS) ist verbunden mit muskelschmerzen, Veränderungen im autonomen Nervensystem (ANS) und Angst. Ziel: Machbarkeit einer Follow-up-Studie und Wirksamkeit der Behandlung des Reaset Ansatzes auf ANS, Muskelschmerzen und State und Trait- Angst bestimmen. Methoden: 15 Patienten mit ABS und Muskelschmerzen wurden in 3 Gruppen eingeteilt (Körper, Kopf-Hals, Kopf-Hals-Körper). Jede Gruppe erhielt eine einzige 25 Minuten dauernde 'Reaset Approach’-Behandlung. Herzfrequenzvariabilität (HRV), elektro-dermale Aktivität (EDA), State-Trait-Angstsinventar (STAI) und Muskelschmerzen (SF-MPQ) wurden gemessen. Ergebnisse: Die HRV-wert: SDNN ist bei 13 von 15 Probanden erhöht, während SD1 und SD2 bei 12 von 15 Probanden zugenommen hat. EDA war bei 10 von 14 Probanden reduziert. Die State-Angst hat bei allen Probanden und die Trait-Angst bei 14 der 15 Probanden abgenommen. Muskelschmerzen waren bei alle Probanden anschließend an und drei Tage nach der Intervention reduziert. Schlussfolgerung: Diese Pilotstudie hat gezeigt, dass eine Follow-up-Studie fortgesetzt werden kann, sofern kleinere Änderungen durchgeführt werden. Die 'Reaset Approach’ hat einen günstigen Einfluss auf die ANS, State-Trait-Angst und Muskelschmerzen. Ergebnisse zwischen den Gruppen sind unterschiedlich. Die Interventionsgruppen mit einschließlich der Kopf-Hals-Modalitäten zeigten bessere Ergebnisse..:I. Abstract (En) III II. Abstract (De) IV III. Table of Contents V IV. Index of figures VIII V. Index of tables IX VI. Index of abbreviations X 1 Introduction 1 2 Background 2 2.1 Work-related musculoskeletal pain 2 2.2 Work-related stress 3 2.3 Osteopathy and the autonomic nervous system 3 2.4 Stress, pain and osteopathy 4 3 Questions 6 3.1 Feasibility 6 3.2 Treatment effect 6 4 Methods 7 4.1 Study design 7 4.2 Participants 8 4.2.1 Inclusion criteria 8 4.2.2 Exclusion criteria 8 4.2.3 Recruitment 8 4.2.4 Randomization 10 4.3 Parameters 11 4.3.1 Heart rate variability 11 4.3.2 Electro-dermal activity 11 4.3.3 State anxiety 11 4.3.4 Trait anxiety 12 4.3.5 Perceived pain 12 4.4 Measuring Instruments 13 4.4.1 Heart rate variability 13 4.4.2 Electro-dermal Activity 13 4.4.3 State-Trait Anxiety Inventory 13 4.4.4 Short-Form McGill Pain Questionnaire 13 4.5 Interventions 14 4.5.1 Intervention ‘B’: Body 14 4.5.2 Intervention ‘HN’: Head and Neck 16 4.5.3 Intervention ‘HNB’: Head, Neck and Body 16 4.6 Study flow 18 4.7 Statistics 20 5 Results 21 5.1 Autonomic nervous system: Heart rate variability 21 5.1.1 SDNN 22 5.1.2 SD1 25 5.1.3 SD2 28 5.2 Autonomic Nervous System: Electro-dermal activity 31 5.3 Anxiety 34 5.3.1 State anxiety 34 5.3.2 Trait anxiety 37 5.4 Musculoskeletal pain 39 5.4.1 Visual analogue scale 40 5.4.2 Total Short-Form McGill Pain Questionnaire 43 6 Discussion 46 6.1 Discussion of the method 46 6.2 Discussion of the results 50 6.2.1 Autonomic nervous system 50 6.2.1.1 Heart rate variability 50 6.2.1.2 Electro-dermal activity 51 6.2.2 Anxiety 51 6.2.2.1 State anxiety 51 6.2.2.2 Trait Anxiety 52 6.2.3 Musculoskeletal pain 52 6.3 Suggestions for future research 53 7 Conclusion 54 8 Literature 55 9 Addendum 63 9.1 Table: SF-MPQ with Sensory, Affective and Evaluative dimension 63 9.2 Patient Information Sheet 64 9.3 Structured telephone interview 70 9.4 Structured pre-treatment interview 72 9.5 SF-MPQ permission 73 9.6 SF-MPQ 74 9.7 STAI License 76 9.8 STAI forms Y-1 and Y-2 77

Indiana University-Purdue University Indianapolis (IUPUI) / Autonomic innervation of the heart begins in utero and continues during the neonatal phase of life. A balance between the sympathetic and parasympathetic arms of the autonomic nervous system is required to regulate heart rate as well as the force of each contraction. Our lab studies the development of sympathetic innervation of the early postnatal heart in a conditional knockout (cKO) of Src homology protein tyrosine phosphatase 2 (Shp2). Shp2 is a ubiquitously expressed non-receptor phosphatase involved in a variety of cellular functions including survival, proliferation, and differentiation. We targeted Shp2 in post-migratory neural crest (NC) lineages using our novel Periostin-Cre. This resulted in a fully penetrant mouse model of diminished cardiac sympathetic innervation and concomitant bradycardia that progressively worsen. Shp2 is thought to mediate its basic cellular functions through a plethora of signaling cascades including extracellular signal-regulated kinases (ERK) 1 and 2. We hypothesize that abrogation of downstream ERK1/2 signaling in NC lineages is primarily responsible for the failed sympathetic innervation phenotype observed in our mouse model. Shp2 cKOs are indistinguishable from control littermates at birth and exhibit no gross structural cardiac anomalies; however, in vivo electrocardiogram (ECG) characterization revealed sinus bradycardia that develops as the Shp2 cKO ages. Significantly, 100% of Shp2 cKOs die within 3 weeks after birth. Characterization of the expression pattern of the sympathetic nerve marker tyrosine hydroxylase (TH) revealed a loss of functional sympathetic ganglionic neurons and reduction of cardiac sympathetic axon density in Shp2 cKOs. Shp2 cKOs exhibit lineage-specific suppression of activated pERK1/2 signaling, but not of other downstream targets of Shp2 such as pAKT (phosphorylated-Protein kinase B). Interestingly, restoration of pERK signaling via lineage-specific expression of constitutively active MEK1 (Mitogen-activated protein kinase kinase1) rescued TH-positive cardiac innervation as well as heart rate. These data suggest that the diminished sympathetic cardiac innervation and the resulting ECG abnormalities are a result of decreased pERK signaling in post-migratory NC lineages.

Indiana University-Purdue University Indianapolis (IUPUI) / The heart is a complex organ that is composed of numerous cell types, which must integrate their programs for proper specification, differentiation, and cardiac morphogenesis. During cardiac development the basic helix-loop-helix transcription factor Hand2 is dynamically expressed within the endocardium and extra-cardiac lineages such as the epicardium, cardiac neural crest cells (cNCCs), and NCC derived components of the autonomic nervous system. To investigate Hand2 function within these populations we utilized multiple murine Hand2 Conditional Knockout (H2CKO) genetic models. These studies establish for the first time a functional requirement for Hand2 within the endocardium, as several distinct phenotypes including hypotrabeculation, tricuspid atresia, aberrant septation, and precocious coronary development are observed in endocardial H2CKOs. Molecular analyses reveal that endocardial Hand2 functions within the Notch signaling pathway to regulate expression of Nrg1, which encodes a crucial secreted growth factor. Furthermore, we demonstrate that Notch signaling regulates coronary angiogenesis via Hand2 mediated modulation of Vegf signaling. Hand2 is strongly expressed within midgestation NCC and endocardium derived cardiac cushion mesenchyme. To ascertain the function of Hand2 within these cells we employed the Periostin Cre (Postn-Cre), which marks cushion mesenchyme, a small subset of the epicardium, and components of the autonomic nervous system, to conditionally ablate Hand2. We find that Postn-Cre H2CKOs die shortly after birth despite a lack of cardiac structural defects. Gene expression analyses demonstrate that Postn-Cre ablates Hand2 from the adrenal medulla, causing downregulation of Dopamine Beta Hydroxylase (Dbh), a gene encoding a crucial catecholaminergic biosynthetic enzyme. Electrocardiograms demonstrate that 3-day postnatal Postn-Cre H2CKO pups exhibit significantly slower heart rates than control littermates. In conjunction with the aforementioned gene expression analyses, these results indicate that loss of Hand2 function within the adrenal medulla results in a catecholamine deficiency and subsequent heart failure.

La plupart des études portant sur les commotions cérébrales se sont principalement intéressées aux conséquences de ces dernières sur le cerveau lui-même. Or, le cerveau assure de nombreuses fonctions, étant notamment impliqué dans la régulation du rythme cardiaque. Récemment, des chercheurs ont donc étudié les conséquences de ces commotions cérébrales sur la régulation de la fréquence cardiaque par le cerveau durant un effort physique. Cependant, la majorité des athlètes qui subissent une commotion cérébrale doivent non seulement planifier leur retour au jeu, mais également prévoir un retour au travail ou aux études. Ainsi, l’objectif de ce projet de recherche est d’étudier les conséquences des commotions cérébrales sur la régulation de la fréquence cardiaque par le cerveau durant un effort cognitif. Onze athlètes universitaires ayant subi une commotion cérébrale ainsi que 14 athlètes n’ayant aucun historique de commotion cérébrale ont pris part à l’étude. Les athlètes du groupe commotion ont été évalués en moyenne 14,6 jours (± 7,4 jours) après leur blessure. La fréquence cardiaque des participants a été enregistrée au repos ainsi que durant un effort cognitif qui consistait en une tâche d’alternance (« switch task »). De courts segments de la fréquence cardiaque d’une durée de deux minutes, au repos et durant la tâche cognitive, ont été analysés. Les résultats montrent une augmentation significative de l’entropie approximative chez les athlètes du groupe contrôle durant la tâche cognitive (ρ < 0,05), tandis qu’aucune différence n’a été observée entre l’entropie approximative au repos et celle durant la tâche cognitive chez les athlètes du groupe commotion. Ces résultats suggèrent que des déficits neurologiques liés à la régulation de la fréquence cardiaque peuvent être observés durant une tâche cognitive chez des athlètes ayant récemment subi une commotion cérébrale. / Most studies have focused on the consequences of concussions on the brain itself. However, the brain performs many functions, including regulating heart rate. Therefore, researchers have begun studying the consequences of these concussions on the brain’s heart rate regulation during physical exertion. Most athletes who sustain a concussion need to plan for their return to play as well as a return to work or school. The purpose of this research project was to study the consequences of concussions on the brain’s regulation of heart rate during cognitive effort. This study involved 11 university athletes who sustained a concussion, as well as 14 athletes with no history of concussion. Concussed athletes were assessed an average of 14.6 days (± 7.4 days) after their injury. The participants’ heart rate was recorded at rest and during cognitive effort, which consisted of a switch task. Short segments lasting two minutes at rest and during cognitive task were analyzed. The results show a significant increase in the approximate entropy in the control group during the cognitive task (ρ <0.05), while no difference was observed between the approximate entropy at rest and during the cognitive task in the concussed athletes. These results suggest that neurological deficits related to heart rate regulation may be observed during cognitive task in athletes who recently sustained a concussion.

Le sepsis tardif, défini comme une infection systémique chez les nouveaux nés âgés de plus de 3 jours, survient chez environ 7% à 10% de tous les nouveau-nés et chez plus de 25% des nouveau-nés de très faible poids de naissance qui sont hospitalisés dans les unités de soins intensifs néonatals (USIN). Les apnées et bradycardies (AB) spontanées récurrentes et graves sont parmi les principaux indicateurs précoces cliniques de l'infection systémique chez les prématurés. L'objectif de cette thèse est de déterminer si la variabilité du rythme cardiaque (VRC), la respiration et l'analyse de leurs relations aident au diagnostic de l'infection chez les nouveaux nés prématurés par des moyens non invasifs en USIN. Par conséquent, on a effectué l'analyse Mono-Voie (MV) et Bi-Voies (BV) sur deux groupes sélectionnés de nouveau-nés prématurés: sepsis (S) vs. non-sepsis (NS). (1) Tout d'abord, on a étudié la série RR non seulement par des méthodes de distribution (moy, varn, skew, kurt, med, SpAs), par les méthodes linéaire: le domaine temporel (SD, RMSSD) et dans le domaine fréquentiel (p_VLF, p_LF, p_HF), mais aussi par les méthodes non–linéaires: la théorie du chaos (alphas, alphaF) et la théorie de l'information (AppEn, SamEn, PermEn, Regul). Pour chaque méthode, nous étudions trois tailles de fenêtre 1024/2048/4096, puis nous comparons ces méthodes afin de trouver les meilleures façons de distinguer S de NS. Les résultats montrent que les indices alphaS, alphaF et SamEn sont les paramètres optimaux pour séparer les deux populations. (2) Ensuite, la question du couplage fonctionnel entre la VRC et la respiration nasale est adressée. Des relations linéaires et non-linéaires ont été explorées. Les indices linéaires sont la corrélation (r²), l'indice de la fonction de cohérence (Cohere) et la corrélation temps-fréquence (r2t,f) , tandis que le coefficient de régression non-linéaire (h²) a été utilisé pour analyser des relations non-linéaires. Nous avons calculé les deux directions de couplage pendant l'évaluation de l'indice h2 de régression non-linéaire. Enfin, à partir de l'ensemble du processus d'analyse, il est évident que les trois indices (r2tf_rn_raw_0p2_0p4, h2_rn_raw et h2_nr_raw) sont des moyens complémentaires pour le diagnostic du sepsis de façon non-invasive chez ces patients fragiles. (3) Après, l'étude de faisabilité de la détection du sepsis en USIN est réalisée sur la base des paramètres retenus lors des études MV et BV. Nous avons montré que le test proposé, basé sur la fusion optimale des six indices ci-dessus, conduit à de bonnes performances statistiques. En conclusion, les mesures choisies lors de l'analyse des signaux en MV et BV ont une bonne répétabilité et permettent de mettre en place un test en vue du diagnostic non invasif et précoce du sepsis. Le test proposé peut être utilisé pour fournir une alarme fiable lors de la survenue d'un épisode d'AB tout en exploitant les systèmes de monitoring actuels en USIN. / Late-onset sepsis, defined as a systemic infection in neonates older than 3 days, occurs in approximately 10% of all neonates and in more than 25% of very low birth weight infants who are hospitalized in Neonatal Intensive Care Units (NICU). Recurrent and severe spontaneous apneas and bradycardias (AB) is one of the major clinical early indicators of systemic infection in the premature infant. Various hematological and biochemical markers have been evaluated for this indication but they are invasive procedures that cannot be repeated several times. The objective of this Ph.D dissertation was to determine if heart rate variability (HRV), respiration and the analysis of their relationships help to the diagnosis of infection in premature infants via non-invasive ways in NICU. Therefore, we carried out Mono-Channel (MC) and Bi-Channel (BC) Analysis in two selected groups of premature infants: sepsis (S) vs. non-sepsis (NS). (1) Firstly, we studied the RR series not only by distribution methods (moy, varn, skew, kurt, med, SpAs), by linear methods: time domain (SD, RMSSD) and frequency domain (p_VLF, p_LF, p_HF), but also by non-linear methods: chaos theory (alphaS, alphaF) and information theory (AppEn, SamEn, PermEn, Regul). For each method, we attempt three sizes of window 1024/2048/4096, and then compare these methods in order to find the optimal ways to distinguish S from NS. The results show that alphaS, alphaF and SamEn are optimal parameters to recognize sepsis from the diagnosis of late neonatal infection in premature infants with unusual and recurrent AB. (2) The question about the functional coupling of HRV and nasal respiration is addressed. Linear and non-linear relationships have been explored. Linear indexes were correlation (r²), coherence function (Cohere) and time-frequency index (r2t,f), while a non-linear regression coefficient (h²) was used to analyze non-linear relationships. We calculated two directions during evaluate the index h2 of non-linear regression. Finally, from the entire analysis process, it is obvious that the three indexes (r2tf_rn_raw_0p2_0p4, h2_rn_raw and h2_nr_raw) were complementary ways to diagnosticate sepsis in a non-invasive way, in such delicate patients.(3) Furthermore, feasibility study is carried out on the candidate parameters selected from MC and BC respectively. We discovered that the proposed test based on optimal fusion of 6 features shows good performance with the largest Area Under Curves (AUC) and the least Probability of False Alarm (PFA). As a conclusion, we believe that the selected measures from MC and BC signal analysis have a good repeatability and accuracy to test for the diagnosis of sepsis via non-invasive NICU monitoring system, which can reliably confirm or refute the diagnosis of infection at an early stage.