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Made available in DSpace on 2016-06-02T19:22:11Z (GMT). No. of bitstreams: 1 6251.pdf: 2137348 bytes, checksum: c2a00dd9baf672490949a036d79336a8 (MD5) Previous issue date: 2014-09-26 / Universidade Federal de Minas Gerais / Literature reports that genetic polymorphisms may determine important modulations on athletes phenotypes, such as height, cardiovascular adaptations, use of energy substrates as well as electrolyte and hormonal balance. It is possible that individuals who express the alpha actinin 3 gene (ACTN3; ancestral homozygous RR or heterozygous RX) may offer advantages in movements that require strength and fast twitch compared with individuals with XX genotype. ACTN3 is a sarcomeric Z line component, which is important for the actin filaments anchorage and myofibrillar arrangement maintenance. Regarding AMP deaminase (AMPD1) polymorphism, it has been reported that athletes with the mutant allele (allele T) may present disadvantages in intense and repetitive physical activities, since the enzyme encoded by this gene is responsible for the ATP resynthesis after intense muscle contractions. Polymorphisms in the angiotensin converting enzyme gene (ACE; deletion allele D) and angiotensinogen (AGT; mutated allele T) may favor athletes in activities requiring strength, due to the fact of higher Angiotensin (Ang) II circulating levels. The present study investigated whether polymorphisms in ACTN3, AMPD1, ACE and AGT genes, alone or in combination, may influence the hemodynamic and cardiac parameters as well as soccer players performance during physical tests such as jump, speed and endurance. Saliva from 220 young professional soccer players (14-20 years) from São Paulo Futebol Clube (Brazil) was collected. Then, total DNA was extracted from saliva and polymerase chain reaction (PCR) was used for genotyping of athletes. To provide more reliability to the study, athletes were also separated according to their age. Before this separation, the athletes with the mutation in the ACTN3 gene jumped lower heights in Squat Jump test (SJ) (RR/RX = 33.64 ± 5.31 vs XX = 30.81 ± 4.51 cm, p = 0.007), as well as in the Under (U)-15 (RR/RX = 34.88 ± 5.39 vs XX = 30.59 ± 4.07 cm, p = 0.04) and U- 17 (RR/RX = 35.82 ± 4.35 vs XX = 30.24 ± 5.16 cm, p = 0.01) categories. In the Counter Movement Jump test (CMJ), RR/RX jumped 37.26 ± 5.72 cm and XX 34.12 ± 4.84 cm (p = 0.005). In the U-17 category, RR/RX jumped 38.56 ± 5.69 cm and XX 32.90 ± 6.06 cm (p = 0.02). In the Counter Movement Jump with arms (CMJb) test, with all athletes, RR/RX jumped 43.85 ± 6.38 cm and XX 40.61 ± 5.06 cm (p = 0.009). The speed test (30 m) showed in the U-17 category that RR/RX were faster than the XX athletes (RR/RX = 4.13 ± 0.13 vs XX = 4.27 ± 0 17 s, p = 0.04). Regarding AMPD1 gene, no significant difference was found in the jumps and endurance tests, but in the speed test (10 m), CC athletes were faster than those with CT/TT genotypes (CC = 1.53 ± 0.19 vs CT/TT = 1.62 ± 0.16 s, p = 0.04). Athletes with DD genotype (ACE) jumped significantly higher in CMJb test compared with ID/II (DD = 44.37 ± 6.22 vs ID/II = 42.35 ± 6.23 cm, p = 0.02). In the U-17 category, DD athletes jumped higher in SJ (DD = 38.04 ± 5.00 vs ID/II = 33.16 ± 4.11 cm, p = 0.01), CMJ (DD = 41.03 ± 5.64 vs ID/II = 35.76 ± 4.26 cm, p = 0.01) and CMJb (DD = 48.62 ± 5.98 vs ID/II = 42.42 ± 4.81 cm, p = 0.007). In the endurance test, athletes from U-16 category with genotypes ID/II, traveled greater distances compared with DD (ID/II = 1.467 ± 63.70 vs DD =1.244 ± 64.25 m, p = 0.04). The DD genotype also favored athletes in speed test (30 m), either for players from U-14 category (DD = 4.29 ± 0.19 vs ID/II = 4.40 ± 0.16 s, p = 0.02) or for the U- 17 category (DD = 4.07 ± 0.15 vs ID/II = 4.20 ± 0.13 s, p = 0.04). AGT gene polymorphism did not influence the performance in the tests, but athletes with the mutant genotype (TT) showed greater left ventricle (LV) hypertrophy (114.6 ± 105.2 g/m2 for TT, 92.16 ± 18.88 g/m2 for MT and 94.78 ± 21.08 g/m2 for MM, p = 0.04) without any change in cardiac and other hemodynamic parameters. Greater LV hypertrophy (DD = 96.95 ± 19.96, ID = 90.14 ± 21.58 and II = 91.67 ± 21.09 g/m2, p = 0.04) and higher ejection fraction (DD = 71.73 ± 7.71, ID = 69.48 ± 6.51 and II = 68.59 ± 5.72 %, p = 0.02) were also found in the athletes with the DD genotype. The analysis of genes combination on athletic performance, when characteristics of strength and muscle fast twitch in the ranking by score were taken into account, showed that athletes with the highest scores (5-8) jumped higher than those with lower scores (1-4) in SJ test (score 5 to 8 = 33.80 ± 5.16 vs score 1 to 4 = 31.60 ± 5.22 cm, p = 0.01) and CMJ test (score 5 to 8 = 43.90 ± 6.85 vs score 1 to 4 = 41.87 ± 5.98 cm, p = 0.04). The present results suggest that RR/RX (ACTN3), DD (ACE) and CC (AMPD1) genotypes may benefit soccer players in activities requiring strength and fast twitch. In addition, ID/II genotypes seem to provide more resistance to athletes in endurance activity. In the future, the organization, standardization and ethical responsibility will be required in the management of these genetic markers for use in athletes training process. / Há relatos na literatura de que os polimorfismos genéticos podem determinar importantes modulações nos fenótipos dos atletas, como por exemplo, estatura, adaptações cardiovasculares, utilização dos substratos energéticos bem como balanço eletrolítico e hormonal. É possível que indivíduos que expressem o gene alfa actinina 3 (ACTN3; genótipos RR para homozigotos ancestrais ou RX para heterozigotos) possam apresentar vantagens em movimentos que exijam força e rápida contração muscular quando comparados aos indivíduos com genótipo XX. Isto pelo fato de a ACTN3 ser um componente da linha Z sarcomérica, o qual é importante para o ancoramento dos miofilamentos de actina e manutenção do arranjo miofibrilar. Com relação ao polimorfismo no gene AMP deaminase (AMPD1), tem sido relatado que os atletas que apresentam o alelo mutado (alelo T) possam apresentar desvantagens em atividades físicas intensas e repetitivas, uma vez que a enzima codificada por este gene é responsável pela ressíntese de ATP muscular após intensas contrações. Os polimorfismos nos genes da enzima conversora de angiotensina (ECA; alelo de deleção D) e angiotensinogênio (AGT; alelo T mutado) podem favorecer os atletas em atividades que requeiram força, isto por conta dos maiores níveis circulantes de Angiotensina (Ang) II. Este estudo investigou se os polimorfismos nos genes ACTN3, AMPD1, ECA e AGT, combinados ou não, podem influenciar nos parâmetros hemodinâmicos, cardíacos e no desempenho de jogadores de futebol em testes físico-motores tais como saltos, velocidade e endurance. Foi coletada a saliva de 220 jogadores jovens (14 a 20 anos) das categorias de base profissional do São Paulo Futebol Clube, Brasil. Em seguida, o DNA total foi extraído a partir da saliva e ensaios de reação em cadeia da polimerase (PCR) foram utilizados para a genotipagem dos atletas. Para conferir mais fidedignidade ao estudo, os atletas foram também separados de acordo com a idade. Antes desta separação, os atletas com a mutação no gene ACTN3 saltaram menos no teste Squat Jump (SJ) (RR/RX = 33,64 ± 5,31 vs XX = 30,81 ± 4,51 cm, p = 0,007), assim como nas categorias Sub-15 (RR/RX = 34,88 ± 5,39 vs XX = 30,59 ± 4,07 cm, p = 0,04) e Sub-17 (RR/RX = 35,82 ± 4,35 vs XX = 30,24 ± 5,16 cm, p = 0,01). No teste Counter Movement Jump (CMJ) os RR/RX saltaram 37,26 ± 5,72 cm e os XX 34,12 ± 4,84 cm (p = 0,005). Na categoria Sub-17, detectou-se que os RR/RX saltaram 38,56 ± 5,69 cm e os XX 32,90 ± 6,06 cm (p = 0,02). No teste Counter Movement Jump com os braços (CMJb), com todos os atletas, os RR/RX saltaram 43,85 ± 6,38 cm e os XX 40,61 ± 5,06 cm (p = 0,009). O teste de velocidade de deslocamento (30 m) revelou, na categoria Sub-17, que os RR/RX foram mais velozes que os atletas XX (RR/RX = 4,13 ± 0,13 vs XX = 4,27 ± 0,17 s, p = 0,04). Com relação ao gene AMPD1, nenhuma diferença significativa foi encontrada nos testes de saltos e endurance, porém no teste de velocidade de deslocamento (10 m), os atletas CC foram mais velozes comparados àqueles com genótipos CT/TT (CC = 1,53 ± 0,19 vs CT/TT = 1,62 ± 0,16 s, p = 0,04). Atletas com o genótipo DD (ECA) saltaram significativamente mais alto no teste CMJb comparados aos ID/II (DD = 44,37 ± 6,22 vs ID/II 42,35 ± 6,23 cm, p = 0,02). Na categoria Sub-17, os atletas DD saltaram mais nos testes SJ (DD = 38,04 ± 5,00 vs ID/II = 33,16 ± 4,11 cm, p = 0,01), CMJ (DD = 41,03 ± 5,64 vs ID/II = 35,76 ± 4,26 cm, p = 0,01) e CMJb (DD = 48,62 ± 5,98 vs ID/II = 42,42 ± 4,81 cm, p = 0,007). No teste de endurance, atletas da categoria Sub-16 com os genótipos ID/II, percorreram maiores distâncias comparados aos DD (ID/II = 1.467 ± 63,70 vs DD = 1.244 ± 64,25 m, p = 0,04). O genótipo DD do gene da ECA também favoreceu os atletas no teste de velocidade (30 m), pois jogadores da categoria Sub-14 com o referido genótipo foram mais velozes comparados aos ID/II (DD = 4,29 ± 0,19 vs ID/II = 4,40 ± 0,16 s, p = 0,02). O mesmo pôde ser visto para a categoria Sub-17 (DD = 4,07 ± 0,15 vs ID/II = 4,20 ± 0,13 s, p = 0,04). O polimorfismo no gene AGT parece não influenciar o desempenho nos testes propostos, porém atletas com o genótipo mutado (TT) apresentaram maior hipertrofia do ventrículo esquerdo (VE; 114,6 ± 105,2 g/m2 para TT; 92,16 ± 18,88 g/m2 para MT e 94,78 ± 21,08 g/m2 para MM, p = 0,04), sem qualquer outra alteração nos outros parâmetros cardíacos e hemodinâmicos. Maior hipertrofia do VE (DD = 96,95 ± 19,96; ID = 90,14 ± 21,58 e II = 91,67 ± 21,09 g/m2, p = 0,04) e maior fração de ejeção (DD = 71,73 ± 7,71; ID = 69,48 ± 6,51 e II = 68,59 ± 5,72 %, p = 0,02) também foram encontradas nos atletas com o genótipo DD. A análise da combinação dos genes no desempenho dos atletas, quando se privilegiaram as características de força e explosão muscular no ranqueamento por escore, revelou que os atletas com os escores mais altos (5 a 8) saltaram mais comparados àqueles com escores mais baixos (1 a 4) no teste SJ (Escore 5 a 8 = 33,80 ± 5,16 vs Escore 1 a 4 = 31,60 ± 5,22 cm, p = 0,01) e no teste CMJ (Escore 5 a 8 = 43,90 ± 6,85 vs Escore 1 a 4 = 41,87 ± 5,98 cm, p = 0,04). Os resultados do presente estudo sugerem que os genótipos RR/RX (ACTN3), DD (ECA) e CC (AMPD1) podem beneficiar os jogadores de futebol em atividades que requeiram força e rápida contração muscular. Além disso, os genótipos ID/II parecem proporcionar mais resistência aos atletas em atividade de endurance. Para o futuro, serão necessárias organização, padronização e responsabilidade ética no manejo desses dados genéticos para a utilização no processo de formação de atletas.

A lombalgia mecânica comum (LMC) representa um problema particularmente importante no ambiente ocupacional, muitas vezes associado a incapacidade, afastamento do trabalho e alto custo socioeconômico. O surgimento da neuroimagem funcional permitiu novos conhecimentos sobre a estrutura cerebral e a fisiologia da dor crônica. Embora os aspectos relacionados ao trabalho sejam importantes fatores de risco para a cronicidade, existem poucos estudos que abordam especificamente a fisiopatologia da LMC em indivíduos afastados do trabalho. A esse respeito, questionamos se um fator como a atenção, conhecida como um importante modulador da dor, poderia desempenhar um papel distintivo na modulação da dor nos indivíduos com LMC afastados do trabalho. Objetivos: comparar os correlatos neuronais entre indivíduos com lombalgia mecânica comum com afastamento do trabalho, com indivíduos lombálgicos sem afastamento. Métodos: Foram selecionados 74 indivíduos com LMC crônica, divididos em três grupos: indivíduos com LMC e afastamento do trabalho (LMC/A); indivíduos com LMC sem afastamento do trabalho (LMC) e indivíduos sem qualquer tipo de dor crônica e sem afastamento do trabalho (Controle). O estudo foi realizado no Hospital Israelita Albert Einstein (HIAE). A ressonância magnética funcional (RMf) foi utilizada durante o desempenho de dois paradigmas (dor e atenção). Resultados: Após a estimulação dolorosa, na comparação entre os grupos, verificamos diferença significativa na condição estimulação > repouso, sendo que o contraste LMC > LMC/A mostrou maior resposta hemodinâmica (efeito BOLD) no córtex cingulado anterior e giro frontal superior e médio direito (p < 0,001). No contraste controles > LMC/A, o grupo controle apresentou maior efeito BOLD em região do polo frontal e paracingulado (p = 0,002). Conclusão: Nosso estudo corrobora o conceito de que a presença de dor crônica está associada a uma alteração na plasticidade neuronal em áreas cerebrais que se estendem além das regiões somatossensoriais, para incluir áreas que processam emoções / Chronic low back pain (CLBP) is a particularly important problem in the occupational environment, often associated with incapacity, sick leave and high socioeconomic cost. The emergence of functional neuroimaging allowed new insights into the brain structure and physiology of chronic pain. Although work-related aspects are important risk factors for chronicity, there are few studies that specifically address the pathophysiology of CLBP in individuals with sick leave. In this regard, we questioned whether a factor such as the attention known as an important pain modulator could play a distinctive role in modulating pain in individuals with CLBP with sick leave. Objective The overall objective of this study is to compare the neuronal correlates between groups of individuals CLBP with or without sick leave. Methods We selected 74 individuals, divided into three groups: individuals with CLBP, functional incapacity and sick leave (CLBP_L); individuals with CLBP, functional disability without sick leave (CLBP_NL); individuals without any form of chronic pain and without sick leave (Control). Functional magnetic resonance imaging (fMRI) was used during the performance of two paradigms (pain and attention).Results After painful stimulation, a significant difference was observed in the stimulation > rest condition, while the CLBP > CLBP_L contrast showed a higher hemodynamic response in the anterior cingulate cortex and the right medium /superior frontal gyrus (p < 0.001) and in contrast controls > CLBP_L, the control group presented higher hemodynamic response in the frontal pole and paracingulate region (p = 0.002).Conclusions Our study corroborates the idea that the presence of chronic pain is associated with an alteration in neuronal plasticity involving brain areas linked to emotions and not just somatosensory areas

A hipertensão arterial pulmonar idiopática é uma doença que acomete os vasos arteriais pulmonares, determinando o aumento da resistência vascular pulmonar levando à deterioração hemodinâmica. Avaliamos se a distensibilidade da artéria pulmonar avaliada pela ressonância magnética se correlaciona à resposta ao teste agudo com vasodilatador em pacientes com hipertensão pulmonar. Houve diferença significativa de distensibilidade da artéria pulmonar em pacientes respondedores e não-respondedores. Após a análise dos dados por uma curva ROC, a distensibilidade de 10% distinguiu a população de respondedores de não-respondedores com 100% de sensibilidade e 56% de especificidade / Pulmonary arterial hypertension is characterized by an increase in pulmonary vascular resistance, eventually leading to hemodynamic failure. We assessed whether pulmonary artery distensibility (evaluated by magnetic resonance) correlated with acute vasodilator test response. A statistically significant difference was found in terms of pulmonary artery distensibility in responders and non-responders. A ROC curve showed that 10% distensibility could discriminate responders from non-responders with 100%sensitivity and 56% specificity

L'anévrisme intracrânien est la prédisposition mortelle la plus fréquente chez le sujet jeune. Sa compréhension demeure limitée alors que nous assistons au développement de nouveaux traitements endovasculaires permettant le traitement d'anévrismes de plus en plus complexes. L'essentiel des études sur le sujet repose sur des séries cliniques peu informatives, l'utilisation de méthodes de simulation numérique limitées et cible presque exclusivement les phénomènes mécaniques intrasacculaires sans tenir compte des conséquences de l'anévrisme sur l'artère porteuse. In vitro, l'utilisation d'anévrismes en silicone au sein d'un simulateur cardiovasculaire a permis d'objectiver un impact de l'anévrisme sur l'écoulement au sein du vaisseau porteur caractérisé par une diminution de sa résistance. In vivo, cet effet a été objectivé et mesuré en IRM de flux par l'analyse des courbes de débit volumétrique. Le flux sanguin en aval des anévrismes était caractérisé par une démodulation systolo-diastolique avec diminution des index de résistance et de pulsatilité. Cet effet était fortement corrélé au volume de l'anévrisme. Les stents flow diverters permettaient une « reconstruction hémodynamique » mesurable du vaisseau porteur en restaurant un flux normo-modulé et des index de pulsatilité et de résistance dans les limites de la normale. Une méthode originale pour la segmentation de l'artère carotide interne en IRM en contraste de phase 2D a été proposée. Elle se base sur l'application de la Transformée de Fourier sur les images de phase et la prise en compte de la cohérence temporelle des vitesses au sein du voxel. La méthode a été caractérisée et comparée à deux méthodes de référence / Intracranial aneurysms are the most common lethal predisposition amongst young adults. Its understanding remains limited to date while the development of new innovative endovascular treatments are increasingly available and allow for the treatment of more and more complex aneurysms with a non negligeable rate of complications. Most of the previous studies on intracranial aneurysms are based on low informative clinical series and the use of limited numerical simulation methods. They almost exclusively target the intrasaccular mechanical phenomena irrespective of the changes in the parent vessel induced by the aneurysm. In vitro, the use of silicone aneurysms embedded in a cardiovascular simulator showed an impact of the aneurysm on the the parent vessel flow conditions characterized by a decrease of its resistance. In vivo, flow MRI allowed to quantify this effect by analyzing the volumetric flow rate curves. Downstream to the aneurysm, the blood flow was dampened and presents a systolic diastolic demodulation with a collapse of resistive and pulsatility indexes. This effect was strongly correlated to the aneurysm volume. The flow diverter stents allowed for a measurable « hemodynamic reconstruction » of the parent vessel by restoring a normo modulated flow, and normal resistive and pulsatility indexes. An original method for the segmentation of internal carotid artery in 2D phase contrast MRI was proposed. It is based on the application of the Fourier Transform on the phase images and by taking into account the temporal coherence of velocities within the voxel. The method was characterized and compared to two reference methods

L’objectif général de ce travail était d’évaluer l’effet du diabète de Type 1 et de l’hyperglycémie chronique (reflétée par un niveau élevé d’HbA1c), chez des patients indemnes de complications micro et macrovasculaires, sur la disponibilité en oxygène (O2) au niveau musculaire et cortical et ses répercussions sur l’aptitude physique aérobie. Dans un premier temps, nous nous sommes attardés à étudier l’effet du diabète et des niveaux élevés d’HbA1c sur les différentes étapes de la cascade d’oxygène (à savoir la diffusion alvéolo-capillaire, le transport artériel et la libération de l’O2 au niveau musculaire) ainsi que sur l’oxygénation musculaire estimée par la Spectroscopie dans le proche Infra-Rouge (NIRS) durant un exercice incrémental et voir les répercussions possibles sur la consommation maximale d’oxygène (&#12310;V &#775;O&#12311;_2max). Nous avons montré que les patients DT1 présentent une capacité de diffusion alvéolo-capillaire ainsi qu’une capacité de transport artériel d’O2 comparable aux sujets sains. En revanche, les patients ayant un niveau élevé d’HbA1c présentent une altération de &#12310;V &#775;O&#12311;_2max ainsi qu’une réduction du volume sanguin musculaire (reflétée par une baisse de l’hémoglobine totale) et une nette baisse de la déoxyhémoglobine (HHb) au niveau du muscle actif aux intensités proches de l’exercice maximal. Ce dernier résultat pourrait s’expliquer par l’affinité plus importante de HbA1c pour l’O2 et/ou une altération de la redistribution de débit sanguin entre les vaisseaux nutritifs et non nutritifs. L’altération du volume sanguin au niveau musculaire chez les patients présentant un mauvais contrôle glycémique peut prévenir les cliniciens du dysfonctionnement de la microcirculation survenant avant même qu’une microangiopathie se manifeste à l’état clinique (Étude 1). Dans un second temps, nous nous sommes intéressés à la fonction cérébrale. Notre objectif étant d’évaluer l’hémodynamique cérébrale durant un exercice incrémental maximal. Nous avons trouvé une altération de l’hémodynamique cérébrale (baisse de l’hémoglobine totale) aux intensités proches de l’exercice maximal chez les patients DT1 qui présentent un mauvais contrôle glycémique (Étude 2). Ces deux travaux nous montrent bien que les sujets diabétiques de type 1 indemnes des complications micro et/ou marcovasculaires présentent une faible aptitude physique aérobie qui peut s’expliquer à la fois par une altération de l’oxygénation musculaire et cérébrale. Ces études mettent également en évidence l’intérêt d’associer la NIRS avec un exercice maximal. Ce dernier place les tissus en situation de besoin maximal en O2 ce qui permet de mettre en exergue des altérations fonctionnelles de la microcirculation avant même l’apparition de complications microvasculaires détectables par les tests cliniques habituels. / This study sought to investigate whether type 1 diabetes and high levels of glycated hemoglobin (HbA1c) influence oxygen supply including alveolar capillary diffusion, oxygen delivery and release, to active muscle and prefrontal cortex during maximal exercise. We first studied the effect of high level of HbA1c on oxyhemoglobin dissociation at the active muscle measured by Near Infra-Red Spectroscopy (NIRS) during maximal exercise. We found that alveolar capillary diffusion and arterial oxygen content was comparable between patients with type 1 diabetes and healthy subjects. However, patients with inadequate glycemic control but without any clinically detectable vascular complications displayed an impaired aerobic capacity as well as a reduction in blood volume and a dramatic impairment in deoxyhemoglobin (HHb) increase in active skeletal muscle during intense exercise. The latter supports the hypotheses of an increase in O2 affinity induced by hemoglobin glycation and/or of a disturbed balance between nutritive and nonnutritive muscle blood flow. Furthermore, reduced exercise muscle blood volume in poorly controlled patients may warn clinicians of microvascular dysfunction occurring even before overt microangiopathy (Study 1). Secondly, we aimed at investigating prefrontal cortex hemodynamic during an incremental maximal exercise in patients with uncomplicated type 1 diabetes, taking into account chronic glycemic control. We observed that levels and changes in regional cerebral blood volume – as reflected by change in total hemoglobin – were lower at high intensities of exercise in patients with inadequate glycemic control (Study 2).In summary, the physiological stimulus of maximal exercise coupled with NIRS measurement highlighted subclinical disorders of both cerebral hemodynamic and muscle oxygenation in poorly-controlled patients with type 1 diabetes albeit free from any clinical microangiopathy.

INTRODUÇÃO: O benefício de um programa de treinamento físico em pacientes com insuficiência cardíaca tem sido bastante documentado. Contudo, pouco se conhece a respeito dos benefícios de um programa de treinamento fisco nãosupervisionado na qualidade de vida, capacidade física e no controle neurovascular, após uma fase inicial de treinamento físico supervisionado. Foi ainda objetivo deste estudo, analisar a efetividade de um programa de atividade física na redução dos níveis de catecolaminas plasmáticas, NT-ProBNP e Interleucina 6 em pacientes com disfunção ventricular na vigência de betabloqueadores. MÉTODOS: Trinta pacientes (idade 54±1,7 anos) com disfunção ventricular esquerda acentuada foram inicialmente selecionados para o estudo. Os pacientes foram divididos em 2 grupos: o grupo controle (n=12); e o grupo treinamento físico (n=18). No início do estudo todos tiveram a qualidade de vida avaliada pelo questionário de Minnesota, e foram dosados os níveis de Interleucina 6, NT-ProBNP, e catecolamina plasmática. A atividade nervosa simpática muscular foi registrada diretamente no nervo fibular através da técnica da microneurografia. O fluxo sangüíneo muscular em antebraço foi avaliado pela técnica da pletismografia de oclusão venosa. Ambos os procedimentos foram registrados em repouso e durante o exercício isométrico a 30% da contração voluntária máxima. A capacidade física foi avaliada por meio da ergoespirometria. O grupo treinamento foi submetido inicialmente a quatro meses de treinamento físico supervisionado composto por 3 sessões de 60 minutos por semana, mantendo uma freqüência cardíaca correspondente a 10% abaixo do ponto de descompensação respiratória determinado pela ergoespirometria. Após a fase de treinamento físico supervisionado, os pacientes foram orientados a realizar quatro meses adicionais de treinamento físico de forma não-supervisionada, na mesma freqüência e intensidade determinadas durante a fase de treinamento supervisionado. A medida da qualidade de vida, atividade nervosa simpática muscular, fluxo sangüíneo muscular e análise laboratorial foram repetidas em 4 meses em ambos os grupos e no oitavo mês apenas no grupo submetido ao treinamento físico. RESULTADOS: Após os quatro primeiros meses, o grupo treinado apresentou melhora na qualidade de vida comparado ao grupo controle (39±6 vs 42±5 pontos; p=0,014). A atividade nervosa simpática muscular em repouso e durante o exercício isométrico a 30% da contração voluntária máxima também apresentaram melhora (47±5 vs 73±6 impulsos/ 100 bat; p=0,0052) e (61±5 vs 77±6 impulsos/ 100 bat; p=0,034), respectivamente. O fluxo sangüíneo muscular em antebraço em repouso aumentou no grupo treinado (1,96±0,11 vs 1,51±0,12 ml/min/100 ml tecido; p=0,015). Quatro meses de treinamento físico não-supervisionado foram efetivos na manutenção dos benefícios na qualidade de vida (52±6 vs 36±6 vs 33±5 pontos; p=0,0001), no fluxo sangüíneo muscular em antebraço, tanto em repouso (1,62±0,47 vs 1,93±0,56 vs 2,18±0,63 ml/min/100 ml tecido; p=0,03) como durante o exercício isométrico (2,04±0,11 vs 2,69±0,18 vs 2,74 ±0,2 ml/min/100 ml tecido; p=0,0016) e na capacidade física (71±9 vs 84±9 vs 88±9 Watts; p=0,0073). Não houve diferença nas medidas seriadas de NTProBNP, Interleucina 6 e de catecolaminas plasmáticas. CONCLUSÕES: O treinamento físico não-supervisionado por quatro meses, após uma fase de treinamento físico supervisionado, foi efetivo na manutenção dos benefícios na qualidade de vida, capacidade física e no fluxo sangüíneo muscular em antebraço. Não houve diferença nas medidas laboratoriais dos pacientes com disfunção ventricular esquerda treinados por oito meses / INTRODUCTION: The benefits of a physical training program in patients with heart dysfunction have been well described. However little is know about the response of a home-based exercise training in quality of life, physical capacity and neurovascular control in patients with heart failure, after a initial four months supervised training. The second objective of this study was to analyze the effectiveness of a exercise program on catecholamine, NT-ProBNP and Interleukin 6 in patients with heart dysfunction receiving beta-blockers. METHODS: Thirty patients (age 54±1,7 years) with severe heart dysfunction were initially enrolled in the protocol. They were divided in two groups; a control group (n=12) and a exercise group (n=18). Initially, both group had the measuring of quality of life by Minnesota questionnaire, Interleukin 6, NT-ProBNP and catecholamine. Muscle sympathetic nerve activity was recorded directly from fibular nerve using the technique of microneurography. Forearm blood flow was measured by venous plethysmography. Both procedures were recorded at rest and during 30% of maximal isometric contraction. The exercise group was submitted initially to fourmonths supervised exercise training program consisted of three 60 min exercise XXIX sessions per week, at heart rate levels that corresponded up to 10% below the respiratory compensation point. After the supervised period, the exercise group was instructed to perform an additional four-months home-based exercise training in the same frequency and intensity they had usually done. The quality of life, muscle sympathetic nerve activity, forearm blood flow and laboratory analysis were repeated at four months in both groups and only in the exercise group at eight months. RESULTS: After the initial 4 months the exercise group improved the quality of life compared to the control group (39±6 vs 42±5 units; p=0,014). The muscle sympathetic nerve activity at rest and during 30% of the maximum isometric contraction was also improved (47±5 vs 73±6 bursts/100 heart beat; p=0,0052) and (61±5 vs 77±6 bursts/100 heart beat; p=0,0276), respectively. The forearm blood flow at rest reduced in the exercise group (1,96±0,11 vs 1,51±0,11ml/min/100 ml tissue; p=0,015). An additional 4 month home-based exercise training was effective on the maintenance of the benefits on quality of life ( 52±6 vs 36±6 vs 33±5 points; p=0,0001), forearm blood flow at rest (1,62±0,47 vs 1,93±0,56 vs 2,18±0,63 ml/min/100 ml tissue; p=0,03), and during 30% of the maximum isometric contraction (2,04±0,11 vs 2,69±0,18 vs 2,74 ±0,2 ml/min/100 ml tissue; p=0,0016) and on physical capacity (71±9 vs 84±9 vs 88±9 Watts; p=0,0073). There was no difference on the measurements of NT-ProBNP, Interleukin 6 and catecholamine. CONCLUSIONS: A home-based exercise training for four months, after a supervised phase, was effective on the maintenance of the benefits of quality of life, physical capacity and forearm blood flow. There was no difference on the laboratorial measurements after an eight months physical training on patients with heart dysfunction

INTRODUÇÃO: A aspiração traqueal (ASP) é um procedimento de rotina em pacientes sob ventilação mecânica, porém em algumas situações pode não ser eficiente. Como adjuvante usa-se a técnica \"Bag-Squeezing\" (BS) que consiste na hiperinflação manual associada à compressão torácica manual expiratória seguida ASP. Embora efetiva esta técnica pode apresentar algumas limitações como a desconexão do ventilador mecânico, além do controle precário do pico de pressão inspiratória (PPI) e pico de fluxo inspiratório (PFI). Como opção, podemos substituir o ressuscitador manual pelo próprio ventilador mecânico, alterando seus parâmetros e evitando assim a desconexão. Propusemos padronizar esta técnica e denominá-la PEEP-ZEEP (PZ); realizando-se a inflação dos pulmões aumentando a PEEP em 10 cmH2O, por 5 ciclos respiratórios, seguido de rápida descompressão pulmonar pela redução abrupta da PEEP até 0 cmH20, simultâneo à compressão torácica manual. OBJETIVOS: Avaliar o comportamento hemodinâmico, da troca gasosa e da mecânica respiratória, na aplicação das técnicas ASP, BS e PZ e seus efeitos na remoção de secreções brônquicas em pacientes ventilados mecanicamente. MÉTODO: 1ª etapa - \"Pacientes sem secreção brônquica\" estudamos prospectivamente 45 pacientes, divididos aleatoriamente em 3 grupos iguais, avaliamos os efeitos da aplicação das técnicas ASP, BS e PZ nos parâmetros hemodinâmicos, na troca gasosa e na mecânica pulmonar antes, imediatamente após, do 1o ao 10o e 30o min. subseqüentemente à aplicação das técnicas. Na 2ª etapa - \"Pacientes com hipersecreção brônquica\" foram estudados prospectivamente 15 pacientes ventilados mecanicamente, que apresentavam hipersecreção brônquica submetidos às técnicas ASP, BS e PZ aleatoriamente em intervalos de 2 horas, avaliamos as mesmas variáveis da 1a etapa porém acompanhamos os pacientes até 120 min. após cada intervenção. Avaliamos também o peso úmido da secreção brônquica, bem como sua reologia. RESULTADOS: 1ª etapa - Semelhantes quanto aos dados antropométricos e tempos de CEC, nossos pacientes apresentavam 59±10anos, IMC 26±3,2 kg/m2 e tempo médio de CEC de 91±19min. Houve elevação da FC somente após aplicação de BS (98±8; 106±10). PAM e SpO2 não se alteraram, observamos elevação na ETCO2 (36±6; 37±6 e 37±7; 39±8) nas técnicas BS e PZ respectivamente. Não verificamos alteração na mecânica respiratória até 30 min. após aplicação das técnicas. Durante a execução das técnicas BS e PZ respectivamente observamos elevação significante do PPI (63±17 vs 17±3), PPLATÔ (22±5 vs 26±3), PFI (154±27 vs 20±5) e PFE (86±20 vs 64±10). 2ª etapa - Nossos pacientes apresentavam 66±14anos, IMC 24±3,2 kg/m2 e tempo médio de CEC de 113±54min. A FC e a SpO2 não se alteraram, porém houve elevação significante da PAM imediatamente após a aplicação de ASP, BS e PZ (85±12 vs 101±16, 90±12 vs 100±14, 84±10 vs 97±11). Na PZ houve diminuição na ETCO2 (36±6 vs 35±7). Não observamos alteração na mecânica respiratória até 120 min. após aplicação das técnicas. Durante a execução das técnicas BS e PZ respectivamente observamos elevação significante do PPI (45±22 vs 27±3) e PFI (91±21 vs 44±17), porém a PPLATÔ (27±15 vs 26±3) e o PFE (71±20 vs 64±13) foram semelhantes entre elas. Não encontramos diferença significante no peso úmido do muco ASP(0,91±1), BS(1,09±1) e PZ(0,53±0,5), nem na análise do deslocamento e da viscoelasticidade. CONCLUSÕES: As técnicas não alteraram significantemente o comportamento hemodinâmico, de troca gasosa e de mecânica respiratória. BS e PZ foram capazes de aumentar o PFE, porém a nova proposta PZ permite maior controle das variáveis de mecânica respiratória, possibilitando monitoramento das pressões e fluxos impostos ao sistema respiratório. Todas as técnicas foram capazes de remover secreções brônquicas de forma semelhante. / INTRODUCTION: Tracheal suction (TS) is a routine procedure in patients submitted to mechanical ventilation. In association, the bag-squeezing (BS) technique is described as a manual hyperinflation associated to a manually assisted coughing followed by TS. This technique might present few limitations as its mechanical ventilator disconnection and poor control of variables such as peak inspiratory pressure (PIP) and peak inspiratory flow (PIF). We might substitute the manual ressuscitator by the mechanical ventilator itself altering its parameters and avoiding its disconnection. We proposed to standardize this technique and named it PEEP-ZEEP (PZ); inflate the lungs increasing the PEEP in 10 cmH20, trough 5 respiratory cycles, followed by an abrupt pulmonary decompression bringing the PEEP to 0 cmH20, associated to the manually assisted coughing. OBJECTIVES: Assess the hemodynamic, gas exchange and respiratory mechanics variables during the use of TS, BS and PZ techniques and assess their effects in the removal of bronchial secretions in mechanically ventilated patients. METHODS: First step - \"Patients without bronchial secretions\" - We assessed 45 patients prospectively, divided randomically into three groups, evaluating the effects of TS, BS and PZ techniques in the haemodynamics, gas exchange and respiratory mechanics variables before, immediately after, in the 10th and 30th minute after the technique. Second step - \"Patients with bronchial secretions\" - We assessed 15 mechanically ventilated patients submitted to the TS, BS and PZ techniques within 2 hours, evaluating the same variables of the first step. However we followed-up the patients until 120 minutes in each technique. We also assessed the humid weight of the bronchial secretions as well as the mucus reology. RESULTS: Results were similar when related to antropometric data and ECC period. First step - There was a raise in the HR after the BS procedure (98±8; 106±10), MAP and SpO2 did not altered. Raise in ETCO2 (36±6; 37±6 and 37±7; 39±8) in the BS e PZ techniques respectively, without alteration in the respiratory mechanics until 30 minutes after the techniques. During the BS e PZ techniques, we observed a significant increase in PIP (63±17 vs 17±3), PPLATEU (22±5 vs 26±3), PIF (154±27 vs 20±5) and PEF (86±20 vs 64±10). Second step - HR and SpO2 did not altered, there was a significant increase in MAP immediately after the TS, BS and PZ techniques (85±12 vs 101±16, 90±12 vs 100±14, 84±10 vs 97±11). The PZ technique had lower ETCO2 (36±6 vs 35±7). We did not observed any respiratory mechanics alteration until 120 minutes after the techniques. During the BS e PZ techniques, respectively, we observed an increase in the PIP (45±22 vs 27±3) and PIF (91±21 vs 44±17), however the PPLATEU (27±15 vs 26±3) and PEF (71±20 vs 64±13) were similar. The PZ technique (0,54±0,5) remove less humid weight mucus when compared to TS (0,91±1) and BS (1,09±1), but the analysis by simulated cough machine PZ (25?11) was better then TS(33?13). CONCLUSION: All techniques remove bronchial secretions and did not altered the hemodynamic, gas exchange and respiratory mechanics significantly. BS and PZ were able to enhance the PEF, however the new proposition of the PZ technique allows a better control of the respiratory mechanics variables.

L’implantation valvulaire aortique percutanée (TAVI) a émergé comme une alternative à la chirurgie pour les patients avec sténose sévère et haut risque chirurgical. Cette technique s’étend à une population plus large (e.g. anatomie plus complexe, risque chirurgical plus bas), ainsi qu'au traitement Valve-in-Valve (ViV) des bioprothèses (BPs) chirurgicales défaillantes. Cependant, deux complications majeures en limitent la généralisation. En TAVI « classique », la présence de fuites péripothétiques a été associée à une mortalité augmentée. Les effets du surdimensionnement de la prothèse percutanée pour assurer son étanchéité, ou de la forme de l’anneau souvent non circulaire, sur la performance hémodynamique, sont mal connus. En ViV, la présence de hauts gradients est fréquente et associée à une mortalité augmentée. Les BPs de taille nominale ≤ 21 mm et le mode de dégénérescence par sténose, facteurs mis en cause dans la sténose résiduelle et associés à une mortalité augmentée, ne sont pas assez spécifiques et il n’existe actuellement aucune recommandation pour le traitement des petites BPs. Par ailleurs, le bénéfice hémodynamique réel du ViV par rapport aux statuts avant ViV n’a pas été étudié.L’objectif général de ce travail doctoral est de comprendre les interactions entre la prothèse percutanée et l’anneau aortique ou la BP à traiter, impliquées dans la performance hémodynamique, en particulier dans des conditions d’implantation complexes, afin d’étendre les indications du TAVI. En ViV, le défi est de préciser les facteurs associés à sa performance et son utilité hémodynamique et de proposer des stratégies d’implantation afin d’optimiser le succès de la procédure. / Transcatheter aortic valve implantation (TAVI) has emerged as an alternative to surgery for patients with severe aortic stenosis and high surgical risk. This technique is extending to a wider population (e.g. with more complex anatomy or lower surgical risk), as well as to patients with degenerated surgical bioprostheses (BPs). However, two major concerns remain limiting. Regarding “classical TAVI”, periprosthetic leaks have been associated with increased mortality. Oversizing is used to secure the device within the aortic annulus which is often non circular. The effects of oversizing and annulus shape on the hemodynamic performance are unknown. Regarding ViV implantations, elevated post-procedural gradients are common and have been associated with increased mortality. The principal factors associated with this residual stenosis as well as with increased risk of mortality, have been BPs label size ≤ 21 mm and mode of failure by stenosis. These factors are not specific enough and there is currently no recommendation for the treatment of small BPs. Besides, the actual hemodynamic benefit associated with ViV has not been evaluated (vs. pre ViV status).The general objective of this work is to understand the interactions between the transcatheter prosthesis and the aortic annulus or the BP to be treated, which impact the hemodynamic performance, especially in complex conditions of implantation, in order to extend the indications of TAVI. In the context of ViV, the objective is to specify the factors associated with the hemodynamic performance and utility of the treatment. The final aim is to provide strategies of implantation in order to optimize the success of the procedure.

Le cadre neuroconstructiviste du développement cognitif, en considérant la variabilité des contraintes qui agissent dès la conception et façonnent le développement, apparaît pertinent pour considérer l’influence des expériences sensorielles précoces sur le développement neurocomportemental des nouveau-nés prématurés. Ils évoluent dans un environnement particulier et ont une vulnérabilité aux troubles neurodéveloppementaux, auxquels des atypies du traitement tactile et temporel sont associées. L’objectif de ce travail de thèse est d’étudier les compétences tactiles et temporelles des nouveaux nés prématurés, et d’évaluer l’effet de l’environnement précoce sur ces perceptions. La perception tactile passive et la cognition ont été étudié auprès de 61 nouveau-nés prématurés (nés entre 32 et 34SA) à 35 semaines d’âge corrigé. Les réponses d’orientation manuelle lors de stimulations tactiles passives du membre supérieur ont été mesurées lors d'un paradigme d’habituation et de déshabituation (changement de localisation ou pause dans la séquence de stimulation). Les prématurés montrent une réponse d'orientation manuelle aux stimuli, qui diminue lors de la répétition, indépendamment de son emplacement sur le bras. L'habituation est retardée chez les sujets nés le plus tôt, à un petit poids et ayant vécu davantage d’expériences douloureuses. Enfin, les prématurés perçoivent les changements de localisation du stimulus et l'intervalle interstimulus, ce qui suggère un développement prénatal des capacités de traitement temporel. Ces capacités de traitement temporel et leur utilisation pour générer une prédiction sensorielle ont été évaluées au cours d’une seconde étude. 19 nouveau-nés prématurés (nés entre 31 et 32 SA) ont été soumis à une séquence tactile (régulière ou irrégulière) aux âges corrigés de 33 et 35 SA. Les variations de flux sanguin cérébral été mesurées. Aux deux âges corrigés, les stimuli tactiles sont associés à une réponse hémodynamique au sein du cortex somatosensoriel. À 33 semaines d’âge gestationnel corrigé les omissions dans la séquence sont associées à une augmentation du flux sanguin cérébral, qui indique que les prématurés forment des prédictions sensorielles, indépendamment du groupe expérimental. Ce travail de thèse permet de mieux caractériser les capacités de traitement tactile et temporel des nouveau-nés prématurés, qui manquent d’investigations récentes et approfondies. De plus, il apporte des arguments rationnels qui pourraient permettre de proposer des thérapies sensorielles à ces patients, basées sur leurs capacités de perception. / The neuroconstructivist theoretical framework of cognitive development, taking into account the variability of the constraints that act from the conception to shape development, is relevant to consider the early influence of sensory experiences on the neurobehavioral development of preterm neonates. They evolve in a particular environment and are vulnerable to neurodevelopmental disorders, to which atypical tactile and temporal processing are associated. The aim of the thesis is to study tactile and temporal abilities in preterm newborns and to evaluate the effect of the early environment on these perceptions. We included 61 preterm neonates (born between 32 and 34 weeks of gestational age (wGA)). At 35 weeks of corrected gestational age, we measured orienting responses (forearm, hand, and fingers movements) during vibrotactile stimulation of their hand and forearm, during a habituation and dishabituation paradigm, the dishabituation being either a location change or a pause in the stimulation sequence. Preterm newborns displayed a manual orienting response to vibrotactile stimuli which significantly decreased when the stimulus was repeated, regardless of the stimulated location on the limb. Habituation was delayed in subjects born at a younger gestational age, smaller birth weight, and having experienced more painful care procedures. Preterm neonates perceived changes in stimulus location and interstimulus time interval, suggesting a prenatal development of temporal processing capacities. These temporal processing abilities and their use to generate sensory prediction are being evaluated in a second study. 19 premature neonates (born between 31 and 32wGA) were presented with a tactile sequence (regular or irregular) at 33 and 35 weeks of corrected GA. Variations in cerebral blood flow were measured. At both corrected GA, tactile stimuli are associated with a hemodynamic response in the primary somatosensory cortex. At 33 weeks of corrected GA, omissions in the sequence are associated with an increase in cerebral blood flow, which indicates that premature neonates form sensory predictions, regardless of their experimental group. This thesis work allows to better characterize the tactile and temporal processing abilities in premature neonates, which lack recent and thorough investigation. In addition, it provides rational arguments that could help to propose sensory therapies to these patients, based on their perceptual abilities.