Introdução: A correta localização do sítio de obstrução nas vias aéreas superiores (VAS) possibilita melhores resultados de tratamento para os pacientes com Síndrome da Apneia Obstrutiva do Sono (SAOS). A endoscopia com sono induzido (DISE) com propofol permite esta avaliação, mas o sono induzido pelo propofol altera a arquitetura do sono, abolindo a presença do sono REM (rapid eye movement). Objetivos: Avaliar as alterações promovidas pelo propofol nos principais parâmetros respiratórios por meio do exame de polissonografia (PSG) nos pacientes portadores de SAOS com predomínio no sono REM (SAOS-R). Descrever os achados da DISE nesses pacientes, comparando-os aos achados da manobra de Müller e às descrições na literatura. Casuística e Métodos: Foram estudados 12 indivíduos não obesos com SAOS-R (confirmado por PSG noturna diagnóstica recente), submetidos a dois exames polissonográficos diurnos, com e sem indução do sono com propofol. O propofol foi utilizado via endovenosa em infusão contínua e controlada por bomba de infusão alvocontrolada (Diprifusor®). Os parâmetros comparados entre os exames foram: IAH (índice de apneia e hipopneia), IA (índice de apneia), IH (índice de hipopneia) e saturação de oxi-hemoglobina (SaO2) mínima e média. Além desses parâmetros, os sítios de obstrução das VAS encontrados na DISE foram comparados com os observados na avaliação ambulatorial com os indivíduos em estado de vigília. Resultados: Não foi evidenciado sono REM em nenhum exame realizado com propofol. O IAH, IA e IH do exame com propofol não apresentaram diferença estatística quando comparados com os exames diurnos sem indução e PSG noturna. A SaO2 média apresentou diferença estatística entre os três exames, sendo menor nas PSGs com indução do sono utilizando propofol, tanto em relação ao exame sem sedação (p<0,0001) quanto ao noturno (p=0,004). A SaO2 mínima foi semelhante entre as PSGs com sedação e noturnas, mas foi significativamente menor nos exames com sedação em relação aos sem sedação diurnos (p=0,011). Quando houve diferença significativa, esta ocorreu em torno de 2 a 3%. A análise de concordância para a classificação de VOTE (velum, oropharynx, tongue base and epiglottis) na avaliação ambulatorial e na DISE não demonstrou nenhuma concordância para todas as estruturas avaliadas (Kappa = - 0,029 em palato, 0,1 em orofaringe, 0,16 em base da língua e 0,0 em epiglote). Os resultados demonstraram que, apesar de o propofol influenciar a arquitetura do sono, abolindo o sono REM, os principais parâmetros utilizados na avaliação dos pacientes com SAOS-R, permaneceram inalterados, ou foram clinicamente irrelevantes. Conclusão: Assim, quando utilizado por infusão contínua, o propofol demonstrou ser uma droga segura na avaliação endoscópica dos indivíduos com SAOS-R para a determinação dos sítios de obstrução, acrescentando informações importantes para o correto tratamento. Ainda, a PSG sob sono induzido com propofol manteve os principais parâmetros ventilatórios em comparação à PSG sob sono espontâneo. / Introduction: The correct localization of upper airway obstruction induces the patients with obstructive sleep apnea syndrome (OSAS) to present better treatment results. Drug induced sleep endoscopy (DISE) with propofol allows this evaluation, but changes the sleep architecture, abolishing the presence of REM sleep. Objecives: To evaluate the changes promoted by propofol on the main respiratory parameters of polysomnography (PSG) in patients with REM-related OSAS (REM-OSAS). To describe the endoscopic findings in these patients, and to compare them to the outpatient Müller\'s maneuver and to the findings described in literature. Casuistic and Methods: In this study, 12 non-obese subjects with REM-OSAS (confirmed by recent nocturnal PSG) underwent two polysomnographic examinations during the day, with and without sleep induction with propofol. Propofol was used intravenously in continuous infusion controlled by target-controlled infusion pump (Diprifusor®). The parameters compared between the examinations were: AHI (apnea-hypopnea index), AI (apnea index), HI (hypopnea index) and both minimal and mean oxihemoglobin saturation (SaO2). Besides these parameters the sites of upper airway obstruction found in DISE were compared with those found in awake outpatient evaluation. Results: REM sleep was not achieved in any moment, in any patient, when propofol was infused. The AHI, AI and HI during infusion with propofol showed no statistical difference when compared with both diurnal test without propofol and diagnostic nocturnal PSG. Mean SaO2 showed statistical difference between the 3 tests, being lower in PSG with sleep induction with propofol, both for the exam without sedation (p<0.0001) as for and the diagnostic PSG (p=0.004). Minimum SaO2 was similar between examinations with sedation and diagnostic nocturnal PSG, but it was significantly lower in tests with propofol infusion compared with the diurnal exam without sedation (p=0,011). Mean difference, when significant, was about 2 to 3%. The analysis of agreement for the VOTE classification by patient evaluation and DISE showed no agreement in any measured structure (kappa = -0.029 for velum, 0,1 for oropharynx, 0,16 for tongue base and 0,0 for epiglottis). The results demonstrate that although propofol influences sleep architecture, abolishing REM sleep, the main respiratory parameters remained unchanged in patients with REMOSAS. Conclusions: Thus, target-controlled infusion of propofol is a safe method for endoscopic evaluation of patients with REM-OSAS, in order to determine the sites of obstruction, and it adds important information for proper treatment. Yet, PSG during DISE with propofol was related to manteinance of the most important ventilatory parameters when compared with PSG under spontaneous sleep.

A apneia obstrutiva do sono é uma síndrome que produz múltiplas comorbidades, aumentando significativamente a taxa de mortalidade dos seus portadores. A atresia maxilar vem sendo descrita como um dos fatores etiológicos da SAOS, entretanto não existem estudos que demonstrem a eficácia no tratamento em adultos com consequente redução dos eventos obstrutivos durante o sono. Este trabalho tem como objetivo principal a verificação da expansão rápida da maxila cirurgicamente assistida (ERMCA), nos eventos obstrutivos do sono e demais parâmetros polissonográficos, na sonolência diurna e no comportamento morfométrico da via aérea. A amostra foi realizada em indivíduos adultos com apneia obstrutiva do sono (SAOS), atresia maxilar e mordida cruzada. O método adotado foi um ensaio clínico prospectivo com 16 participantes (7 mulheres / 9 homens) com idade de 40,23 ± 10,23, todos portadores de SAOS comprovada por polissonografia (PSG) de noite toda (IDR superior a 5), atresia maxilar e mordida cruzada posterior. Previamente todos participantes foram submetidos a uma tomografia computadorizada (TC) da via aérea superior e foi aplicado o teste da Escala de Sonolência de Epworth (ESE). Todos os pacientes foram então submetidos à ERMCA, e posteriormente, todos os exames foram refeitos para comparação. Foi constatada uma redução no IDR de 35,46 ± 38,54 para 16,07 ± 19,73, uma redução média de 54,68% (p=0,0013) e no IAH em 56,24% (33,23 ± 39,54 para 14,54 ± 19,48: p=0,001), uma redução dos índices de microdespertares e dessaturação, além da melhora de diversos parâmetros polissonográficos. O ESE apresentou uma melhora de 12,50 ± 5,32 para 7,25 ± 3,53 (p<0,001). A via aérea total ampliou em média 23,99% (p=0,016), mas de uma maneira mais expressiva na sua metade inferior (28,63% p=0,008). Em relação aos resultados obtidos por meio da ERMCA observou-se uma melhora da SAOS, redução dos índices relacionados aos distúrbios respiratórios durante o sono, de microdespertar e de dessaturação, ampliação da via aérea, principalmente na metade inferior, além de melhorar a sonolência diurna, devolvendo- a para a normalidade. / Obstructive sleep apnea syndrome (OSAS) is a condition that produces multiple comorbidities, significantly increasing the mortality rate of affected individuals. Maxillary atresia is being described as one of the etiological factors of OSAS, although there are no studies demonstrating the efficacy of treatment in adults with a consequent reduction of obstructive events during sleep. The main objective of the present study was to determine the effects of surgically assisted rapid maxillary expansion (SARME) on obstructive sleep events and all other polysomnography (PSG) parameters, on daytime sleepiness and on the morphometric behavior of the airways. The study was conducted on adult individuals with OSAS, maxillary atresia and crossbite. The method involved a prospective clinical assay with 16 participants (7 women/9 men) aged 40.23 ± 10.23 years, with OSAS confirmed by all-night PSG (respiratory disorder index (RDI) higher than 5), maxillary atresia and posterior crossbite. All participants were first submitted to computed tomography of the upper airways and to the Epworth Sleepines Scale (ESS) test. All patients were then submitted to SARME and all exams were later repeated for comparison. RDI was reduced from 35.46 ± 38.54 to 16.07 ± 19.73, (a mean reduction of 54.68%, p=0.0013), the apnea-hypopnea index (AHI) was reduced from 33.23 ± 39.54 to14.54 ± 19.48 (a mean reduction of 56.24%, p=0.001), and micro-awakenings and desaturation were also reduced. The ESS score improved from 12.50 ± 5.32 to 7.25 ± 3.53 (p<0.001). Mean total airway area was increased by 23.99% (p=0.016), although in a more expressive manner in the lower half (28.63%, p=0.008). The results obtained by SARME revealed an improvement of OSAS, a reduction of the indices related to respiratory disorders during sleep, of micro-awakennings and of desaturation, as well as airway expansion, especially in the lower half, and improvement of daytime sleepiness with a return to normality.

Made available in DSpace on 2016-01-26T12:51:26Z (GMT). No. of bitstreams: 1 carolinegabrielemarques_tese.pdf: 1078800 bytes, checksum: 0c7b0504e85857d877828a3f432fe74e (MD5) Previous issue date: 2006-09-25 / This study aims to identify associated characteristics of craniofacial skeletal and pharyngeal soft tissues, in lateral cephalometric teleradiography and their possible association with clinical and polyssonographic findings, observing anatomical areas which most influenced the upper airway obstruction. To evaluate a predicting cephalometric pattern for Sleep Apnea Hipopnea Obstructive Syndrome (SAHOS), a sample of 40 subjects was divided into two experimental groups: patients with mild to moderate and severe SAHOS, previously submitted to polyssonographic study, according to their Apnea or Hipopnea Índex (AHI), comparing them with a control group, 10 subjects, with no sleep disorder. The first experimental group had an AHI=15 <30 (moderate sleep apnea). The second group, an AHI> or = 30 (severe sleep apnea). After the results and the statistical methods used to compare the different studied groups, the conclusion was that the SAHOS patients when compared with the control group presented: some positional alterations in their skeletal anatomical structures, mainly a lowering of the hyoide bone in relation to the cervical vertebrae; mandilbular retrusion, increased dimensions of the pharyngeal soft tissues, increased length and width of the soft palate with a decrease of the posterior and superior airway space. / O propósito deste estudo é identificar associação entre as características craniofaciais esqueletais e de tecidos moles em telerradiografias cefalométricas laterais com os dados clínicos e polissonográficos, verificando as áreas anatômicas que mais contribuem para a obstrução das vias aéreas superiores nos pacientes com Síndrome da Apnéia Hipopnéia Obstrutiva do Sono (SAHOS). Para avaliar se existe um padrão cefalométrico previsível para a Síndrome da Apnéia Hipopnéia Obstrutiva do Sono, foram comparadas as diferenças das médias das dimensões esqueléticas craniofaciais e dos tecidos moles da faringe, em norma lateral, de uma amostra de 40 indivíduos, divididos em 2 grupos-teste, com da Síndrome da Apnéia Hipopnéia Obstrutiva do Sono Moderada e Síndrome da Apnéia Hipopnéia Obstrutiva do Sono Grave, previamente submetidos ao estudo polissonográfico e um grupo controle de 10 indivíduos sem a doença. Pertenciam ao primeiro grupo teste os pacientes com Índice de Apnéia e Hipopnéia (IAH) > 15 < 30 (apnéia do sono moderada) e ao segundo grupo teste os pacientes com Índice de Apnéia e Hipopnéia (IAH) &#8805; 30 (apnéia do sono grave). Diante dos resultados obtidos e após a aplicação dos métodos estatísticos usados para comparação dos diferentes grupos estudados, concluiu-se que os pacientes apnéicos quando comparados com o grupo controle apresentaram: alterações no posicionamento das estruturas anatômicas esqueletais, principalmente um posicionamento inferior do osso hióide em relação às vértebras cervicais, retrusão mandibular, dimensões aumentadas dos tecidos moles faringeanos, aumento no comprimento e largura do palato mole com diminuição do espaço aéreo póstero-superior.

Face aux problématiques d’accès, de désertification médicale et de qualité des soins, la loi « Hôpital, Patients, Santé, Territoires » (HPST), votée en 2009, représente un socle pour la réorganisation des soins primaires en France. L’accent est mis sur la collaboration entre les professionnels de santé et l’optimisation des compétences de chacun. Le pharmacien d’officine se trouve au coeur de cette loi. Grâce à son accessibilité, sa formation et sa proximité avec les patients sains comme malades, il voit l’opportunité d’étendre ses pratiques au-delà de la simple dispensation des médicaments en fournissant directement des soins au patient. Cette proposition n’est pas une exception française mais s’inspire des expériences internationales et du concept de « soins pharmaceutiques ». Le pharmacien écossais peut désormais être payé à la capitation pour délivrer des consultations pharmaceutiques lors du renouvellement d’ordonnance au patient atteint de maladie chronique; le pharmacien anglais peut prescrire des médicaments dans le cadre d’un plan de gestion clinique et recevoir un honoraire de dispensation; le pharmacien suisse peut organiser des réunions de discussion avec les médecins; et le pharmacien portugais peut vacciner son patient au sein de l’officine. Les illustrations de la diversification des pratiques du pharmacien d’officine sont donc variées et se replacent dans leur contexte national. L’enjeu est aujourd’hui de comprendre les conditions et les effets d’un ensemble d’innovations techniques, organisationnelles et sociales qui pourraient être en faveur du développement des soins pharmaceutiques en France. Ce travail de thèse a pour objectif de nourrir les débats autour de cette problématique. Un état des lieux de la profession en France et une enquête d’opinion auprès des futurs pharmaciens montrent que le contexte sanitaire, professionnel, économique est propice au développement des pratiques du pharmacien et que l’avenir des soins pharmaceutiques trouve un écho favorable auprès des pharmaciens de demain. Cependant, nombreux sont les facteurs qui peuvent constituer des obstacles à leur diffusion (Chapitres 1 et 2). D’un point de vue économique, d’après une revue de littérature systématique sur l’efficience des soins pharmaceutiques en Europe, les services de surveillance médicamenteuse, de médication officinale, de collaboration entre les professionnels de santé et de promotion de la santé pourraient être, dans certaines conditions, des interventions coût-efficaces d’un point de vue collectif (Chapitre 3). Mais qu’en est-il en France ? On ne dispose pas de travaux sur le sujet. Deux travaux originaux - une étude de cohorte (exposés/non exposés) et une analyse coût-efficacité -, que nous avons menés, se focalisant sur l’implication du pharmacien d’officine dans le dépistage d’une maladie chronique (le syndrome d’apnées du sommeil) montrent que les coûts engendrés par la mise en place d’une telle intervention sont sous certaines conditions compensés par les gains générés, et les résultats sont en faveur de l’implantation du service en pratique de routine (Chapitre 4). / Facing the issues of access, quality and proximity, the "Hospital, Patients, Health and Territories" (HPST) law, passed in 2009, constitutes a basis for the reorganization of primary care in France. The healthcare reform emphasizes on the collaboration between healthcare professionals and the optimization of their skills. The community pharmacist is on the forefront of this reform. Through its accessibility, its training and its proximity with healthy and sick patients, community pharmacists have the opportunity to broaden the scope of their practices beyond the merely dispensing of medication by delivering patient care. This proposal is not a French exception but takes inspiration from international experiences and the concept of "pharmaceutical care." The Scottish pharmacist can now be paid by capitation to renew a prescription for a patient with chronic illness; the English pharmacist can prescribe medication as part of a clinical management plan and receive a dispensing fee, the Swiss pharmacist can organize meetings with general practitioners and in Portugal, pharmacists can vaccinate a patient in the pharmacy. Pharmaceutical care practices are diversified and depend on national context. The challenge today is to understand the conditions and consequences of technical, organizational and social innovations that could be in favor of the development of pharmaceutical care in France. The objective of the thesis is to feed into the debates around this problematic. An overview of profession in France and an original opinion survey of future pharmacists show that the healthcare, professional and economic contexts are suitable to develop pharmaceutical care and future pharmacists are in favor of it. However, there are many barriers to their spread in routine practice (Chapters 1 and 2). From an economical perspective, a systematic review of the literature on the efficiency of pharmaceutical care in Europe show that drug monitoring services, prescription for minor ailments, collaboration between health professionals and health promotion interventions could be cost-effective from a collective point of view under certain conditions (Chapter 3). What about France? There is no study on this topic. We conducted two original studies - a cohort study (exposed / unexposed), and a cost-effectiveness analysis which focused on the involvement of the pharmacist in screening for chronic disease (sleep apnea syndrome). We show that the costs of implementing such an intervention are offset by the gains under certain conditions, and the results are in favor of the implementation of the service in routine practice (Chapter 4).

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Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Le syndrome d’apnées obstructives du sommeil (SAOS) est associé à de nombreuses co-morbidités métaboliques et cardiovasculaires. L’hypoxie intermittente chronique, une des composantes du SAOS, induit des mécanismes intermédiaires délétères tels que stress oxydatif, inflammation, insulino-résistance ou encore dyslipidémie, à l’origine de ces comorbidités. Ces mécanismes intermédiaires sont également communs à d’autres pathologies respiratoires chroniques telles que la bronchopneumopathie chronique obstructive (BPCO) et le syndrome d’obésité hypoventilation (SOH).L’hypoxie intermittente et les mécanismes intermédiaires associés sont aussi à l’origine de l’existence et de la progression de la stéatopathie métabolique (« non alcoholic fatty liver disease »). Ce lien entre pathologies respiratoires chroniques et atteinte hépatique est un mécanisme essentiel mais plus récemment étudié des co-morbidités dans le SAOS et la BPCO. Différents biomarqueurs cardiométaboliques ont donc été étudiés dans ces pathologies respiratoires chroniques à la fois pour caractériser les co-morbidités et l’atteinte systémique et pour apprécier l’impact de différentes thérapeutiques. La première partie de cette thèse sera consacrée à une revue systématique des différents biomarqueurs cardio-métaboliques liés à chacune de ces 3 pathologies respiratoires chroniques : SAOS, BPCO et SOH.Le traitement du SAOS par pression positive continue (PPC) a un effet bénéfique sur les symptômes fonctionnels liés à cette pathologie. Cependant, l’impact de la PPC sur d’autres conséquences cardio-métaboliques délétères du SAOS reste encore à démontrer par des essais randomisés contrôlés, notamment sur l’atteinte hépatique.Dans la seconde partie de cette thèse, nous détaillerons l’impact de la PPC sur les différents marqueurs cardiométaboliques du SAOS à l’aide d’une revue systématique puis d’une étude randomisée contrôlée sur l’impact de la PPC sur les marqueurs d’atteinte hépatique.Par ailleurs, les patients atteints de SAOS, BPCO ou SOH reçoivent du fait de leur polypathologie (multimorbidité) des traitements médicamenteux multiples qui visent à contrôler au mieux les co-morbidités. Il est donc primordial de considérer la prise en charge globale de ces patients du point de vue de leurs traitements instrumentaux (PPC et ventilation non invasive) mais aussi en considérant l’impact des traitements médicamenteux associés. En effet, les traitements médicamenteux peuvent interférer avec la sévérité de la pathologie elle-même et impacter les biomarqueurs liés aux comorbidités associées. La troisième partie de cette thèse sera consacrée à l’étude d’un antihypertenseur chez le patient SAOS et envisagera l’influence des médicaments sur la pertinence de l’usage des bicarbonates comme marqueurs diagnostiques du SOH.En conclusion, nous insisterons sur la nécessité d’une prise en charge intégrée multi systémique et d’une prise en charge personnalisée de ces patients. / Obstructive sleep apnea (OSA) is associated with related metabolic and cardiovascular comorbidities. Chronic intermittent hypoxia the hallmark of OSA induces deleterious intermediary mechanisms such as oxidative stress, systemic inflammation, insulin resistance and dyslipidemia. Cardiovascular and metabolic comorbidities are also key features of other chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and obesity hypoventilation syndrome (OHS). Chronic hypoxia and deleterious intermediary mechanisms also trigger occurrence and progression of non alcoholic fatty liver disease. This link between chronic respiratory diseases and liver injury is observed through modifications of specific liver biomarkers in OSA and COPD. A variety of cardiometabolic biomarkers have been studied for stratification of cardio-metabolic risk and assessing treatment impact in chronic respiratory diseases. The first part of this PhD thesis is a systematic review of cardio-metabolic biomarkers in 3 respiratory diseases: OSA, COPD and OHS.Continuous positive airway pressure (CPAP) the first line therapy for OSA improves symptoms and quality of life. However, CPAP effects on cardio-metabolic consequences remains still debated. In the second part of the PhD thesis, we will address CPAP impact on different cardiometabolic biomarkers and more specifically in markers of liver injury by reporting original results of a randomized controlled trial (RCT).Polypharmacy is usual in patients with OSA, COPD or OHS. Beyond CPAP or non invasive ventilation treatment, it is essential address the contribution of associated medications. Indeed, pharmacological treatments can interfere with the severity of the disease and control of associated comorbidities. The third part of the thesis will present a RCT evaluating Bosentan in hypertensive OSA patients and will present how medications for comorbidities decrease bicarbonate diagnosis value for OHS.We will conclude by underlining the crucial importance of personalized medicine and integrated care in chronic respiratory diseases.

Le syndrome d’apnées obstructives du sommeil (SAOS) est associé à la survenue de neuropathies optiques, en particulier la neuropathie optique ischémique antérieure aigue non artéritique (NOIAA-NA). Parmi les mécanismes d’apparition de cette neuropathie et potentiellement associés au SAOS, la dysrégulation et l’inflammation vasculaires pourraient jouer un rôle. Il n’existe aucune donnée dans la littérature sur l’effet de l’hypoxie intermittente (HI) chronique sur la fonction vasculaire de l’œil.Le but de ce travail était de développer des techniques d’évaluation de la fonction vasculaire oculaire chez le rat et de les appliquer à l’étude des conséquences vasculaires oculaires de l’HI. Ainsi, deux approches complémentaires ont été développées : 1) un prototype de fluxmètre laser Doppler (LDF) adapté au rongeur pour l’évaluation in vivo de la perfusion sanguine rétinienne et de la tête du nerf optique (TNO) et 2) le modèle d’étude de l’artère ophtalmique (AO) du rat par myographie vasculaire, in vitro.La mise au point du LDF chez le rat sain a permis de valider la pertinence du signal provenant des artères rétiniennes. A l’inverse, nos données invalident l’intérêt de la mesure au niveau de la TNO. En réponse à l’inhalation d’oxygène pur, nous observons une diminution de 17,0 ± 13,7 % de la vélocité artérielle rétinienne (VelART). Nous n’observons pas de variation significative de VelART lors d’injection intra-carotidienne d’endothéline 1 (ET-1) malgré une forte vasoconstriction des vaisseaux rétiniens. Les perspectives consistent à associer une caméra de haute résolution à un système bidirectionnel de LDF. L’étude de la réactivité de l’AO par myographie chez le rat soumis à 14 jours d’HI a mis en évidence une augmentation de la contraction à l’ET-1, associée à une augmentation de la réponse médiée par les récepteurs de type A (ETRA)et à une surexpression des ETRA au sein de l’AO. La relaxation NO-dépendante était diminuée chez le rat HI, et associée à un effet prédominant des produits vasoconstricteurs du cytochrome P450. Ces réponses étaient associées à une augmentation de la présence d’anions superoxyde dans la paroi de l’AO. Des études complémentaires sont nécessaires pour explorer les mécanismes à l’origine des ces altérations vasculaires, en particulier le rôle du stress oxydant. / Obstructive sleep apnea (OSA) has recently been associated with the occurrence of optic neuropathies, especially acute non-arteritic anterior ischemic optic neuropathy (NAION). Among the mechanisms of NAION onset potentially associated with OSA, vascular dysregulation and inflammation may play a role. There is still no data on the effect of chronic intermittent hypoxia (IH) on vascular function of the eye. The purpose of this work was to develop techniques for assessing rat ocular vascular function and apply them to the study of the ocular vascular consequences of IH. Thus, two complementary models have been developed: 1) a laser Doppler flowmeter (LDF) prototype adapted for rodents, to evaluate in vivo retinal and optic nerve head (ONH) blood perfusion and 2) in vitro model of rat ophthalmic artery (OA) study by myography. Preliminary work on healthy rat enabled us to validate the relevance of retinal arteries LDF signal, but not that of the ONH. Retinal blood velocity (VelART) dropped by 17.0 ± 13.7% in response to pure oxygen inhalation. We did not observe any significant change in VelART signal after intracarotidian endothelin 1 (ET -1) injection, despite strong vasoconstriction of retinal vessels. OA reactivity study by myography in rats exposed to a 14-day IH showed increased contraction to ET-1, associated with an increased endothelin receptor A-mediated (ETRA) response and ETRA overexpression within the AO. NO-dependent relaxation is reduced in IH rats, and associated with a shift towards vasoconstrictive effects of cytochrome P450 products. These responses were associated with an increase in superoxide anions in the OA wall. Further studies are needed to explore the underlying mechanisms of these vascular changes, particularly the role of oxidative stress. Understanding of the LDF signal is partial and should be further explored to permit application to the study of IH rat.

Made available in DSpace on 2016-12-23T13:54:31Z (GMT). No. of bitstreams: 1 Nathalia Silveira Finck.pdf: 1726183 bytes, checksum: 40947138e78192ac535b3646b56a67ab (MD5) Previous issue date: 2013-08-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O objetivo dessa dissertação foi investigar as alterações temporomandibulares, craniofaciais e posturais associadas à respiração bucal, além de avaliar a relação entre sinais clínicos e sintomas de distúrbios respiratórios do sono (DRS) em escolares respiradores bucais, na faixa etária de 7 a 14 anos. Trata-se de um estudo caso-controle, com amostra de 147 escolares, sendo 73 com respiração bucal (RB) e 74 com respiração nasal (RN), avaliados através de anamnese, exame clínico e testes respiratórios. Os escolares diagnosticados como respiradores bucais responderam a um questionário sobre a autopercepção de sintomas de DRS na infância, com foco em problemas do sistema mastigatório, nasais e do sono. A presença de respiração bucal foi estatisticamente significativa para as seguintes alterações: ausência de selamento labial (OR= 29.70); desvio durante abertura da boca (OR= 24.63); palato atrésico (OR= 5.07); assimetria facial (OR= 5.06); índice de Mallampati III e IV (OR= 2.85); má oclusão Classe II (OR=2.67); hipertrofia de conchas nasais (OR= 2.19). Não houve diferença significativa entre os grupos para as alterações posturais. Nos escolares RB, problemas na ATM e acordar com dor de cabeça foram associados à má oclusão Classe II e à falta de selamento labial. Dor na nuca e torcicolo foram associados à sobremordida alterada e à anteriorização da cabeça. Problemas com o sono, sonolência diurna, acordar à noite, roncar e dormir de boca aberta foram associados à hipertrofia das tonsilas palatinas e ao índice de Mallampati obstrutivo. A chance de alterações temporomandibulares e craniofaciais ocorrerem em escolares com padrão de respiração bucal foi elevada. O aparecimento de sintomas de DRS na infância parece estar associado à persistência da respiração bucal e suas consequentes alterações craniofaciais, oclusais, posturais e nas vias aéreas superiores / The aim of this study was to investigate the temporomandibular, craniofacial and postural changes associated with mouth breathing and also evaluate the relationship between clinical signs and SDB symptoms in children 7 to 14 years of age. A case-control study with a sample of 147 children, 73 mouth breathers (MB) and 74 nasal breathers (NB), were evaluated by anamnesis, clinical examination and respiratory tests. The schoolchildren diagnosed as MB answered a questionnaire on self-perceived symptoms of SDB, focusing on the masticatory system, nasal and sleep problems. The presence of mouth breathing was statistically significant with the following changes: a lack of lip seal (OR=29.70), a deviation during the opening of the mouth (OR=24.63), an atresic palate (OR=5.07), a facial asymmetry (OR=5.06), an obstructive Mallampati scores (OR=2.85), a Class II malocclusion (OR=2.67) and a turbinate hypertrophy (OR=2.19). No significant difference in postural pattern was found between groups. In the MB group, TMJ problems and wake up with headache were associated with a Class II malocclusion and a lack of lip seal. Stiff neck or neck pain were associated with an altered overbite and a forward head position. Sleep problems, daytime sleepiness, waking at night, snoring and sleeping with the mouth open were associated with a tonsillar hypertrophy and obstructive Mallampati scores. The chances of occurrence of temporomandibular and craniofacial changes were high in the MB schoolchildren. The emergence of the SDB symptoms in childhood appears to be associated with the persistency of the mouth breathing and their consequent craniofacial, occlusal, postural and upper airway s abnormalities