Objectifs: Malgré beaucoup de progrès dans la gestion médico-électrique, certains problèmes demeurent et plusieurs patients souffrant d'insuffisance cardiaque sont encore dans l'impasse. Ainsi, les dispositifs d'assistance ventriculaire gauche (LVAD) ont été développés pour réduire les conséquences de l'insuffisance cardiaque et améliorer la qualité de vie. Malgré les avantages évidents, plusieurs complications : thrombo-embolie, infection dû au câble d'alimentation externe, dépendance aux batteries demeurent. L'ICOMS est un nouveau concept de LVAD mélangeant une pompe entièrement intraventriculaire, synchronisé avec le cœur et relié à une batterie interne. Méthodes et résultats : L'intervalle de fonctionnement prévu est un débit de 0.8 to 6.7 10-5 m3/s à une vitesse de rotation de 733 to 942 rad/s, avec des pressions physiologiques. Le point de fonctionnement choisi pour la conception est un débit de 3.3 10-5 m3/s et 10.6 103 Pa . Dans cette étude, Une simulation numérique est réalisée avec des profils de lames différents pour chaque région de fluide étudié. Les performances telles que l'efficacité, la contrainte de cisaillement sont analysée pour vérifier l'efficacité pour les patients atteints d'insuffisance cardiaque. Afin d'obtenir le meilleur résultat avec le logiciel ANSYS, le modèle k-ε turbulent a été appliquée pour obtenir des caractéristiques d'écoulement entre l'entrée et à la sortie de l'évacuateur du redresseur de la pompe. Les résultats numériques montrent une performance acceptable pour les adultes pour délivrer des pressions physiologiques avec une efficacité hydraulique de 10 à 37% ainsi qu'un niveau acceptable de stress de cisaillement maximale le long de la surface de la partie mobile de la pompe. La deuxième partie de l'étude est une étude expérimentale où un prototype a été testé sur banc d'essai. Les résultats ont montré que la pompe pourrait fonctionner et améliorer le débit cardiaque de 1.7 à 6.7 10-5 m3/s. Les résultats in vitro convergent vers les résultats numériques. Pour les tests in vivo, 6 moutons ont été opérés pour l'implantation du LVAD. L'ICOMS a été implanté dans l'apex du ventricule gauche. Plusieurs paramètres hémodynamiques et échocardiographiques ont été stockés dans des conditions normales ou pathologiques. Conclusion: Nous avons montré que l'ICOMS pourrait présenter un effet potentiel pour réduire les conséquences de l'insuffisance cardiaque. De nouvelles expérimentations sont nécessaires pour confirmer notre résultat et optimiser ce nouveau LVAD / Objectives: Despite much progress in medical-electrical management, some problems remain and several heart failure patients are still in a no option solution. In this way, artificial hearts as Left Ventricular Assist Device (LVAD) have been developed. Despite evident benefits, several complications as thromboembolism, driveline infection, batteries dependency remain. ICOMS is a new LVAD concept mixing a fully intraventricular pump, heat rate-synchronized and connected with intracorporeal batteries. Methods and Results : It is expected to deliver 0.8 to 6.7 10-5 m3/s at rotational speeds of 733 to 942 rad/s over physiologic pressures and has a selected design point of 3.3 10-5 m3/s and 10.6 103 Pa . In this study, the axial blood pump with motor connected to impeller has been selected to numerical simulation. This selection is based on axial flow pump with different blade profile for each fluid region and studied on its performance such as efficiency, wall shear stress and considering effective operation for cardiac failure patients. In order to achieve the best result with the ANSYS software, k-ε turbulent model has been applied to obtain the flow characteristics from inducer inlet to straightener outlet of the pump. Numerical results show acceptable performance to deliver physiologic pressures with hydraulic efficiency of 10 to 37 % as well as acceptable maximum shear stress level along the blade tip surface of the impeller. The second part of the study is an experimental investigation where a prototype device was tested in a test bench circulation loop have shown that the pump could operate and improve the cardiac output of 1.7 to 6.7 10-5 m3/s. In vitro results converge to numerical results. For test vivo 6 sheep were operated for the LVAD implantation with the support of cardiopulmonary by-pass. The ICOMS was implanted into the LV apex. Several hemodynamic and echocardiographic parameters were stored as well as in normal or pathological conditions and analyzed. Conclusion: We showed that the ICOMS could present a potential effect in the LV support reducing the heart failure criteria. As evidence, further experimentations are necessary to confirm our result and to optimize this new LVAD

Diabetes Mellitus is a group of complex and heterogeneous metabolic disorders characterized by hyperglycemia. Even though the condition has been extensively studied, its causes and complex pathologies are still not fully understood. The occurring damage to the pancreatic islets is strikingly heterogeneous. In type 1 diabetes, the insulin producing beta cells are all destroyed within some islets, and similarly in type 2 diabetes, some islets may be severely affected by amyloid. At the same time other islets, in the near vicinity of the ones that are affected by disease, may appear fully normal in both diseases. Little is known about this heterogeneity in susceptibility to disease between pancreatic islets. This thesis examines the physiological and pathophysiological characteristics of islet subpopulations. Two subpopulations of islets were studied; one constituting highly vascularized islets with superior beta cell functionality, and one of low-oxygenated islets with low metabolic activity. The highly functional islets were found to be more susceptible to cellular stress both in vitro and in vivo, and developed more islet amyloid when metabolically challenged. Highly functional islets preferentially had a direct venous drainage, facilitating the distribution of islet hormones to the peripheral tissues. Further, these islets had an increased capacity for insulin secretion at low glucose levels, a response that was observed abolished in patients with recent onset type 1 diabetes.  The second investigated islet subpopulation, low-oxygenated islets, was found to be an over time stable subpopulation of islets with low vascular density and beta cell proliferation. In summary, two subpopulations of islets can be identified in the pancreas based on dissimilarities in vascular support and blood flow. These subpopulations appear to have different physiological functions of importance for the maintenance of glucose homeostasis. However, they also seem to differ in vulnerability, and a preferential death of the highly functional islets may accelerate the progression of both type 1 and type 2 diabetes.

Résumé: Comparées aux classiques insulines humaines régulières (IHR), les insulines analogues ultrarapides (IAUR) ont été conçues pour mieux synchroniser le pic insulinémique avec l’absorption du repas. Le progrès a été démontré chez les patients diabétiques de type 1, mais le contrôle glycémique s’est peu ou pas amélioré chez les patients diabétiques de type 2 (DT2), qu’ils soient sous IAUR ou IHR. Or ces patients constituent 75 % des utilisateurs d’insuline. L’utilité des IAUR est donc toujours débattue. La dose (donc le volume) injectée et le flot sanguin dans le tissu adipeux sous-cutané (FSTA) sont les facteurs majeurs de l’absorption de l’insuline. Les patients DT2, résistants à l’insuline, s’injectent des doses importantes et leur FSTA est de 50 à 70 % plus faible que celui des sujets sains de poids normal (PN). Nous avons montré que l’absorption sous-cutanée des IAUR est diminuée chez les sujets obèses et DT2 (ODT2) par rapport aux sujets PN, que le volume injecté avait un effet délétère additionnel et que le FSTA peut être augmenté de façon pharmacologique avec un agent vasoactif (AV) chez des sujets résistants à l’insuline. Nous suggérons que l’ajout d’un AV à une IAUR va augmenter le FSTA au site d’injection et donc améliorer sa pharmacocinétique (PK) et sa pharmacodynamie (PD). Pour vérifier cette hypothèse, nous avons 1) évalué la réponse du FSTA à 4 AV chez des sujets PN, obèses non-diabétiques et ODT2; 2) évalué la PK/PD et la biodisponibilité de l’IAUR lispro ± AV chez des sujets ODT2; et 3) caractérisé l’expression des cibles des AV dans le tissu adipeux sous-cutané chez les sujets énumérés en 1). Les 4 AV ont augmenté le FSTA des sujets ODT2, mais moins que celui des autres sujets. L’occurrence de la raréfaction et/ou dysfonction microvasculaire chez les sujets ODT2 pourrait expliquer l’hyporéactivité vasculaire aux AV testés. Le plus actif des AV chez les sujets ODT2 a été ajouté à l’IAUR lispro pour améliorer sont absorption sc. Les PK/PD ont été améliorées seulement chez les sujets ODT2 avec une hémoglobine glycosylée A1c ≥ 8 %; c’est-à-dire 4 sujets sur 8. Chez ces derniers, l’absorption de 30 U + AV a été plus rapide de 14 et 71 min à 20 et 80 % de l’aire sous la courbe totale de la lispro plasmatique, respectivement. Chez les 4 autres sujets ODT2, l’absorption de la lispro semble s’être détériorée avec l’AV. Une interaction chimique a peut-être eu lieu entre l’AV et la lispro, ce qui aurait perturbé son absorption. Selon nos résultats, le niveau de contrôle du diabète, le volume d’injection et les caractéristiques chimiques de l’AV seraient des modulateurs de l’efficacité du concept IAUR + AV. Il nous faut maintenant déterminer l’impact de ces facteurs sur la capacité d’un AV à améliorer l’absorption sc de l’IAUR chez les sujets ODT2. / Abstract: Compared to classic regular human insulin (RHI), short-acting insulin analogues were designed to better synchronize plasma insulin increase to food absorption. Although improvements were noted in subjects with type 1 diabetes, slight to no improvement in glycemic control were observed in subjects with type 2 diabetes (T2D) using SAIA instead of RHI. Nevertheless, they represent 75 % of all insulin users. Consequently, the relative useful-ness of SAIA in T2D patients is currently hotly debated. Injected volume and subcutaneous (sc) adipose tissue blood flow (ATBF) are two main factors involved in insulin absorption. In fact, T2D patients use large doses of insulin because of their resistance to insulin and have an ATBF 50 to 70 % lower than lean healthy subjects. We already showed that SAIA absorption is decreased in obese T2D (OT2D) subjects compared to normal weight healthy subjects and that volume has additional detrimental effects. We also showed that ATBF can be increased pharmacologically with vasoactive agents (VA) in healthy and insulin-resistant subjects. Then we suggest that in OT2D subjects, addition of VA to SAIA preparations will locally increase ATBF, improve insulin sc absorption (Pharmacokinetic - PK) and bioavailability, thus insulin hypoglycemic effect (Pharmacodynamic - PD). To test this hypothesis, we 1) assessed ATBF response of 4 selected VA within three experimental groups (normal weight, obese non-diabetic and OT2D subjects); 2) evaluated insulin PK/PD and bioavailability improvement in OT2D subjects after the addition of the best VA to SAIA lispro and 3) characterized expression of selected VA targets in sc adipose tissue biopsies, within equivalent experimental groups, and compared results with ATBF responses. All 4 VA were able to increase ATBF of OT2D subjects but in a less extend than other subjects. The occurrence of microvascular rarefaction and/or dysfunction in OT2D subjects can explain the hyporeactivity to tested VA. Nevertheless, one VA among others was shown more effective to increase ATBF in OT2D subjects and was then tested (mixed) with SAIA lispro. With the AV, PK/PD were improved only in OT2D subjects with A1c glycated hemoglobin ≥ 8 %; 4 subjects on 8. The sc absorption of 30 U + VA was faster by 14 and 71 min for respectively 20 and 80 % of the total area under the lispro plasmatic curve. But the sc absorption with VA appeared blunted with the other subjects. Maybe detrimental chemical interactions occurred between the VA and lispro, which could impede absorption. Our results suggest that diabetes control state, injection volume, and VA chemical characteristics influence the efficacy of our SAIA + VA concept. Further tests are needed to seize the impact of these factors on VA effectiveness in sc absorption improvement of SAIA in OT2D subjects.

Atherosclerosis is an arterial disease that occurs due to the build-up of lipids, cholesterol and other substances in the arterial wall, collectively called plaque, leading to narrowing of the vessel lumen and, in time, disruption to the blood supply. The study of flow through atherosclerotic vessels is especially important since plaques not only cause a reduction in the vessel lumen but can rupture from the arterial wall, causing a blood clot in the vessel that may ultimately lead to heart attack or a stroke. Elevated level of oxidated low density lipoprotein (LDL) is a known risk factor associated with the genesis of atherosclerosis in arterial walls. Previous studies reported in literature have explored the transport of LDL through the arterial wall using analytical and mathematical models. In this work, we have presented a computational framework for the study of LDL transport in the lumen and the porous arterial wall. We have employed a four-layer arterial wall model and used governing equations to model the transport of LDL. We have used physiological parameters for the wall layers from literature and have validated the model based on the calculated filtration velocities and LDL concentration profiles in the arterial wall. We have further used this established model to study the effect of change in permeability and pressure on the LDL concentration. We have also studied the effect of pulsatile flow on the transport of LDL through the porous walls to examine the validity of the initial assumption of steady state and have seen that pulsation increases the time averaged net flux of LDL species by about 20%. We have next modeled a drug-eluting stent (DES), which is one of the popular remedies to cure atherosclerosis. The validation of DES model is followed by a combined study to analyze the effect of stent placement on LDL transport. Although there is no chemical reaction between the drug and LDL, we have noticed recirculation zones near the stent strut which result in accumulation of LDL molecules in the arterial wall. Future studies are aimed at incorporating variable porosity and permeability and a stenosed region in the geometry. The deformation of arterial wall due to pulsatile blood flow may lead to alteration of wall properties, which can give a realistic view of macromolecular transport.

O objetivo deste estudo foi comparar a resposta do vascular durante o teste de estresse mental em adultos sedentários (SED) e fisicamente ativos (FA) com apneia obstrutiva do sono (AOS). Os pacientes não tratados com AOS e sem outras comorbidades foram classificados em SED e FA de acordo com o Questionário Internacional de atividade física. A pressão sanguínea, a freqüência cardíaca, o fluxo sanguíneo do antebraço (FSA) (pletismografia) e a condutância vascular do antebraço (CVA = FSA/pressão sanguínea x 100) foram medidas continuamente em repouso (4 min), seguidas de 3 min do teste Stroop Color Word Test (SCWT) também conhecido como teste de estresse mental. Quarenta pacientes com AOS (homens = 24, idade = 50 ± 1 anos, índice de massa corporal = 29 ± 0,5 Kg/m2, índice de apneia hipopnéia = 39 ± 4 eventos/h) divididos em SED (n = 21) e FA (n = 19) apresentaram diferença significativa na quantidade de tempo gasto em atividade física (17 ± 9 vs. 245 ± 33 minutos/semana, respectivamente). Os grupos foram semelhantes em relação ao sexo, idade, índice de massa corporal, frequência cardíaca do nível educacional e pressão arterial média em repouso, bem como percepção de estresse no final do SCWT. Em contraste, FSA basal (1,7 ± 0,08 mL/min/100mL vs 2,5 ± 0,19 mL/min/100mL) e CVA (1,7 ± 0,07 vs 2,5 ± 0,2) foram significativamente menores no grupo SED quando comaprados a FA, respectivamente (p <0,05). A resposta de frequência cardíaca e pressão arterial ao SCWT foram semelhantes e aumentou em ambos os grupos. O FSA (3,5 ± 0,2 mL/min/100mL vs 2,4 ± 0,14 mL/min/100mL) e a CVA (3,5 ± 0,2 vs 2,3 ± 0,1) durante SCWT foi significativamente menor no grupo SED quando comparados ao grupo FA (P <0,05). Houve uma correlação significativa entre a atividade física no tempo de lazer e FSA (r = 0,57; P <0,05) e CVA (r = 0,48; P <0,05). Conclui-se, que, a resposta vascular nos pacientes com AOS é influenciada pelo nível de atividade física de lazer. O alto nível de atividade física pode proteger a disfunção cardiovascular em repouso e na condição de estresse mental em pacientes com AOS moderado a severo / The objective of this study was to compare a vascular response during the mental stress test in sedentary (SED) and physically active (PA) patients with obstructive sleep apnea (OSA). Patients not treated with OSA and without other comorbidities were classified in SED and PA according to the International Questionnaire of Physical Action. Blood pressure, heart rate, forearm blood flow (plethysmography) and forearm vascular conductance (FVC = FBF / blood pressure x 100) were measured continuously at rest (4 min), followed by 3 min of the test Stroop Color Word Test (SCWT) also known as mental stress test. Forty patients with OSA (men = 24, age = 50 ± 1 years, body mass index = 29 ± 0.5 kg / m2, apnea hypopnea index = 39 ± 4 events / h) divided in SED (n = 19) and PA (n = 19) presented a significant difference in the amount of time spent in physical activity (17 ± 9 vs. 245 ± 33 minutes / week, respectively). The groups are similar in relation to gender, age, body mass index, heart rate at educational level, and mean resting blood pressure, as well as perceived stress at the end of SCWT. In contrast, baseline FBF (1.7 ± 0.08 mL/min/100mL vs 2.5 ± 0.19 mL/min/100mL) and FVC (1.7 ± 0.07 U vs 2.5 ± 0.2 U) were significantly lower without SED group when compared to PA, respectively (p <0.05). The heart rate and blood pressure response to SCWT were similar and increased in both groups. The FBF (3.5 ± 0.2 mL/min/100mL vs 2.4 ± 0.14 mL/min/100mL) and the FVC (3.5 ± 0.2 U vs 2.3 ± 0.1 U) during SCWT was much lower in the SED group when compared to the group PA (P <0.05). There was a significant correlation between physical activity without leisure time and FBF (r = 0.57, P <0.05) and FVC (r = 0.48, P <0.05). In conclusion, the vascular response in OSA patients is influenced by the level of leisure physical activity. The high level of physical activity may protect a cardiovascular dysfunction at rest and mental stress condition in patients with moderate to severe OSA

Introdução: Os distúrbios respiratórios do sono são comuns em pacientes com insuficiência cardíaca. Estudos recentes mostram que pacientes com insuficiência cardíaca apresentam resposta vasoconstritora muscular paradoxal durante a estimulação dos quimiorreceptores centrais e periféricos e que essa resposta está associada à disfunção endotelial e à exacerbação nervosa simpática. Porém, o que não se conhece é se essa resposta está intensificada em pacientes com a coexistência de insuficiência cardíaca e distúrbio respiratório do sono. Objetivos: Testar a hipótese de que: 1) A resposta de fluxo sanguíneo muscular (FSM) durante a hipercapnia e a hipóxia seria menor em pacientes com insuficiência cardíaca e distúrbio respiratório do sono que em pacientes com insuficiência cardíaca sem distúrbio respiratório do sono; e 2) A resposta vasoconstritora mais exacerbada em pacientes com a coexistência de insuficiência cardíaca e distúrbio respiratório do sono estaria associada à disfunção endotelial e/ou à resposta exagerada da atividade nervosa simpática muscular (ANSM). Métodos: Foram avaliados, consecutivamente, 90 pacientes com insuficiência cardíaca, classe funcional II-III (New York Heart Association). Destes, 41 preencheram os critérios de inclusão e, após o exame de polissonografia, foram alocados em dois grupos, de acordo com o índice de apneia e hipopneia (IAH): Grupo IC (IAH < 15 eventos/hora; n=13; 46 (39-53) anos) e Grupo IC+DRS (IAH >= 15 eventos/hora; n=28; 57 (54-61) anos). O consumo de oxigênio no pico do exercício ( 2 pico) e a fração de ejeção do ventrículo esquerdo (FEVE) foram avaliados pelo teste cardiopulmonar em esforço e pela ecocardiografia transtorácica basal, respectivamente. Os FSM do antebraço e da panturrilha (FSMab e FSMp, respectivamente) foram avaliados pela pletismografia de oclusão venosa e a ANSM pela técnica de microneurografia. A pressão arterial média (PAM) e a frequência cardíaca (FC) foram avaliadas batimento a batimento de forma não invasiva (Finometer® PRO). O quimiorreflexo central foi estimulado por meio da inalação de uma mistura gasosa hipercápnica (7% CO2 e 93% O2) e o quimiorreflexo periférico por meio da inalação de uma mistura gasosa hipóxica (10% O2 e 90% N2), com isocapnia mantida, durante 3 minutos. Resultados: Os grupos foram semelhantes em relação à etiologia da insuficiência cardíaca 2 pico, índice de massa corpórea e medicações. No basal, não houve diferença entre os grupos quanto ao FSMab e FSMp, condutância vascular do antebraço (CVab) e panturrilha (CVp). Entretanto, a ANSM foi maior no grupo IC+DRS (P<0,05). Durante a hipercapnia, as respostas vasculares (FSMab, CVab, FSMp, CVp) foram significativamente menores no grupo IC+DRS quando comparadas com o grupo IC (P<0,001, para todas as comparações). De forma semelhante, durante a hipóxia, as respostas vasculares (FSMab, CVab, FSMp, CVp) foram significativamente menores no grupo IC+DRS quando comparadas com o grupo IC (P<=0,001, para todas as comparações). A ANSM, em resposta à hipercapnia e à hipóxia, foi maior no grupo IC+DRS. Durante a hipercapnia, as respostas de FC e PAM não foram diferentes entre os grupos. Durante a hipóxia, as respostas de FC não foram diferentes entre os grupos, enquanto a resposta de PAM foi maior nos pacientes do grupo IC+DRS. Não houve diferença na resposta ventilatória entre os grupos estudados. Conclusão: Pacientes com a coexistência de insuficiência cardíaca e distúrbio respiratório do sono apresentam vasoconstrição muscular paradoxal mais exacerbada que pacientes sem o distúrbio respiratório do sono, durante a hipercapnia e a hipóxia, o que parece estar associada, pelo menos em parte, à maior resposta de ANSM / Background: Sleep disordered breathing is common in heart failure patients. Recent studies show that patients with heart failure have paradox muscle vasoconstriction during the central and peripheral chemoreceptors stimulation, which is associated with endothelial dysfunction and exaggerated sympathetic nerve activity. However, whether this vascular response is more pronounced in patients with the coexistence of heart failure and sleep disordered breathing is unknown. Objectives: To test the hypothesis that: 1) The muscle vasoconstriction responses to hypercapnia and hypoxia would be more pronounced in heart failure patients with sleep disordered breathing than in heart failure patients without sleep disordered breathing; 2) This alteration in vascular responses would be associated with endothelial dysfunction and/or exaggerated muscle sympathetic nerve activity (MSNA) responses. Methods: Ninety consecutive heart failure patients, functional class II-III (New York Heart Association), were screened for the study. Forty-one patients who fulfilled all the inclusion criteria were enrolled and allocated into two groups according to apnea-hypopnea index (AHI): HF (AIH < v15 events/hour; n=13, 46 (39-53) years) and HF+SDB (AIH >=15 events/hour; n=28, 57 (54-61) years). Peak oxygen uptake (Peak 2) and left ventricular ejection fraction (LVEF) were evaluated by maximal incremental exercise test and by echocardiography, respectively. Forearm and calf blood flow (FBF and CBF, respectively) were evaluated by venous occlusion plethysmography and MSNA by microneurography technique. Mean blood pressure (MBP) and heart rate (HR) were evaluated by beat-to-beat noninvasive technique (Finometer® PRO). Central chemoreceptors were stimulated by inhalation of a hipercapnic gas mixture (7% CO2 and 93% O2) and peripheral chemoreceptors by inhalation of a hypoxic gas mixture (10% O2 and 90% N2), with maintenance of isocapnia, for 3 minutes each one. Results: Both groups were similar regarding to heart failure etiology, LVEF, Peak 2, body mass index, and medications. At baseline, there were no differences in FBF and CBF, forearm and calf vascular conductance (FVC and CVC, respectively) between groups. However, the MSNA was greater in HF+SDB group (P < 0.05). During hipercapnia, the vascular responses (FBF, FVC, CBF, CVC) were lower in HF+SDB group when compared to HF group (P < 0.001, to all comparisions). Similarly, during hypoxia, the vascular responses (FBF, FVC, CBF, CVC) were lower in HF+SDB group when compared to HF group (P <= 0.001, to all comparisions). The MSNA in response to hypercapnia and hypoxia was greater in HF+SDB group. During hypercapnia, the HR and MBP responses were not different between groups. During hypoxia, the HR responses were similar between groups, while the MBP responses were greater in HF+SDB group. There was no difference in ventilatory response between groups. Conclusion: Patients with the coexistence of heart failure and sleep disordered breathing have more intense muscle vasoconstriction than patients without sleep disordered breathing, during hypercapnia and hypoxia, which seems to be due, at least in part, to increased responsiveness of MSNA

La pratique d’exercices intenses répétés, entrecoupés de faibles temps de récupération, est susceptible d’engendrer une altération de l’homéostasie et une diminution de la performance chez les sportifs soumis à ce type de contraintes. Dans ce contexte, l’optimisation des processus de récupération est une possibilité forte d’amélioration de la performance et de sa reproduction. Une des principales limites au maintien de la performance de type haute intensité, répété à court terme, est attribuée à la fatigue périphérique, inhérente à l’ensemble des mécanismes de l’excitabilité et de la contraction du muscle squelettique. Cette fatigue périphérique engendre une inadéquation entre les apports et les besoins cellulaires, en oxygène et en nutriments, ainsi qu’une incapacité à éliminer et/ou recycler les produits métaboliques issus de la contraction musculaire. Afin de limiter ces effets, l’augmentation du flux sanguin lors de l’exercice et de la récupération apparaît indispensable au bon rétablissement de l’état d’équilibre de l’organisme et au maintien de la performance sportive. A ce titre, l’électrostimulation neuromusculaire semble être un mode de récupération théoriquement efficace pour augmenter le flux sanguin. Cette présente thèse, comprenant trois études, visait à connaître précisément les effets de l’électrostimulation neuromusculaire - par l’utilisation d’un nouvel appareil issu du domaine médicale - sur la cinétique de récupération de marqueurs de performance, de marqueurs physiologiques et de perception, dans le contexte d’exercices intenses, répétés à court terme. Nous avons émis l’hypothèse qu’une stimulation efficace, induisant une augmentation du flux sanguin, permettrait d’optimiser la récupération à court terme, entre deux exercices de haute intensité. Ces résultats devraient permettre d’optimiser, dans le futur, les stratégies de récupération mises en place après un exercice intense, répété dans de brefs délais / The practice of intense and repeated exercises, interrupted with short recovery times, may induce alterations in homeostasis and a decrease of the performance for athletes who are subject to this type of constraints. In this context, the optimization of the recovery processes is a strong possibility to improve performance and the maintain of it all along the competitive period. One of the main limits in the preservation of performance in type high-intensity, repeated at small interval of time, is attributed to the peripheral fatigue, inherent to all the mechanisms implied in the skeletal muscle excitability and contraction. This peripheral fatigue induces an inadequacy between the contributions and the cellular needs of oxygen and nutrients, and also a disability for disposal or recycling the metabolic by-products stemming from the muscular contraction. In order to limit these effects, the increase in blood flow during exercise and recovery seems essential for the good restoring of the state of physiological balance for the body and the preservation of sport performance. Therefore, the neuromuscular electrical stimulation seems to be, in theory, an effective recovery mode to improve the blood flow. This present thesis, comprising three studies, aimed to know precisely the effects of the neuromuscular electrical stimulation - by the use of a new device stemming from the medical field - on the kinetics of recovery of performance, physiological and perceptual markers, in the context of intense exercises repeated in the short terms. We hypothesized that an effective stimulation, increasing the blood flow would allow to optimize short-term recovery between two high-intensity exercises. These results should contribute to optimize, in the future, the strategies of recovery organized after an intense exercise

A esquizofrenia continua sendo um dos transtornos mais desafiadores para a clínica psiquiátrica, apesar dos estudos atuais que tentam elucidar sua fisiopatologia e buscar novas opções de tratamento. A n-acetilcisteína (NAC) é uma droga utilizada há mais de 30 anos na clínica médica no tratamento da intoxicação por acetaminofeno e como mucolítico na DPOC, entre outros. Evidências recentes apoiam o seu uso no tratamento de diversos transtornos neuropsiquiátricos, como depressão, transtorno afetivo bipolar, dependência química e esquizofrenia. A droga tem como provável mecanismo de ação um aumento na atividade antioxidante através do aumento nos níveis de glutationa (GSH) e modulação da neurotransmissão glutamatérgica. Nas duas últimas décadas, o estudo dos mecanismos neurobiológicos subjacentes aos transtornos psiquiátricos, bem como a investigação dos possíveis mecanismos e regiões cerebrais influenciados por substâncias psicofarmacológicas, recebeu importante contribuição das técnicas de neuroimagem funcional. Apesar disto, até o momento existem poucos estudos que avaliaram os mecanismos centrais relacionados às propriedades antipsicóticas da NAC em humanos. Este estudo tem o objetivo de investigar os efeitos da NAC em indivíduos portadores de esquizofrenia refratária em uso exclusivo de clozapina através de medidas de sintomas positivos e negativos e da avaliação da perfusão cerebral através de ressonância magnética nuclear utilizando a técnica de arterial spin labeling (ASL). Foram avaliados 20 sujeitos com esquizofrenia refratária em uso de clozapina em um estudo com distribuição aleatória, duplo-cego e controlado por placebo, utilizando a dose de 2000mg por dia de NAC. Do total da amostra, 14 tiveram as imagens perfusão sanguínea cerebral analisadas. O estudo teve a duração de oito semanas, com avaliações a cada quatro semanas e realização das RMN no início e ao final do período. Não foram observadas diferenças estatisticamente significativas entre os grupos placebo e NAC nas escalas BPRS e PANSS-N. O grupo que recebeuNAC apresentou mais efeitos colaterais, porém no geral a medicação foi bem tolerada. Também não se observou diferenças no FSC das diversas ROI analisadas. A NAC não produziu mudanças estatisticamente significativas nas escalas de sintomas e no FSC nesta amostra, apesar de outros estudos mostrarem diferenças significativas favorecendo a NAC. O presente estudo não mostrou melhora do FSC, mesmo após oito semanas, o que pode significar que a ASL pode não ser um método adequado para avaliar os efeitos cerebrais desta droga / Schizophrenia continues to be one of the most challenging psychiatric disorders in the clinical practice, despite recent studies that attempt to elucidate its pathophysiology and search for new treatment options. N-acetylcysteine (NAC) is a drug that has been used for more than 30 years in clinical medicine, in situations like acetaminophen intoxication and as mucolytic in COPD, among others. Recent studies support its therapeutic use in neuropsychiatric disorders such as depression, bipolar disorder, substance abuse and schizophrenia. The mechanism of action of NAC seems to occur in antioxidant activity, through the increase of glutathione levels (GSH) and in the modulation of glutamatergic neurotransmission. In the last two decades, the study of the neurobiological mechanisms underlying psychiatric disorders, as well as the investigation of the possible mechanisms and brain areas influenced by psychopharmacological substances received a significant contribution of functional neuroimaging techniques. Despite this, there are few studies that have evaluated the central mechanisms related to the antipsychotic properties of NAC in humans. This study aims to investigate the effects of NAC in subjects with refractory schizophrenia, exclusively on clozapine use, through measure of positive and negative symptoms and the evaluation of cerebral perfusion by magnetic resonance imaging, using the arterial spin labeling technique (ASL) . Twenty subjects with refractory schizophrenia were evaluated in a randomized, double-blind, placebo-controlled study using a dose of 2000mg per day of NAC. From the total sample, 14 had cerebral perfusion images analyzed. The study had a duration of eight weeks, with evaluations at each four weeks and MRI sessions before the beginning of NAC and at the end of the period. The results did not show statistically significant differences between placebo and NAC groups onthe BPRS and PANSS-N scales. The NAC group presented more side effects, although the medication was well tolerated in general. There were also no differences in the cerebral blood flow (CBF) among the regions of interest analyzed. Although there was no difference regarding symptoms scales the CBF in this sample, other studies found differences favoring NAC. The present study did not show changes of the CBF, which might mean that ASL is not an adequate technic to evaluate neurochemical effects of this drug

The inclusion of a new device in clinical practice requires an adequate validation. The original publication which introduced multichannel bioimpedance monitor MBM was focused on discribing its technical parameters and demonstration measurements. Further evaluation desires comparision with other standard measuring device. This thesis describes pulse wave measurement by MBM and by other medical devices used for establishing cardiovascular risk. It proposes the validation experiment with synchronized vascular ultrasonography as a reference method. The process of the experimental measurement, aquired data and following data analysis are described in detail. The outputs of the experiment are statistically evaluated. The MBM’s performance and design of the experiment are discussed.

The thesis deals with LSCI (Laser Speckle Contrast Imaging), an optical method utilizing laser speckle contrast for the estimation of blood flow changes. LSCI is non-invasive and technically not demanding approach, capabilities of which have not yet been fully exploited. The literature review part contains detailed description of the operating principle, imaging techniques, potential for medical applications with considering the limiting factors. The main aim of the thesis is to design and construct a complete LSCI system including appropriate phantoms able to simulate blood flow through the tissue. Imaging algorithms for the obtained data evaluation were implemented in Matlab® development enviroment. Finally, the created system was tested using different acquisition parameters as well as varying the image processing schemes. The resulting qualitative flow images were subsequently discussed and confronted with the theoretical assumptions.