Role of Nkx2.5 on development and electrophysiology of the mouse heart Prague 2015 Bc. Peter Hámor ABSTRACT The objective of this thesis is to investigate the role of Nkx2.5 gene dosage on electrophysiology of the mouse heart in prenatal stage of its development, in which the physiological functions of the heart fail to function properly. The main goal of this work is to search for differences in conduction of electric impulses through the embryonic mouse heart according to their genotype. Special method of capturing the conduction of electric impulse through myocardium was used for this purpose, called optical mapping. Thanks to this method I was able to construct images and videos capturing transition of the impulse with marked beginning of the activation and its direction in the heart. These outputs, or optical maps, help to define anomalies and defects compared with a normal functioning heart. The thesis focuses on the expression of the transcription factor Nkx2.5 and regulatory components related with the correct formation and physiology of the heart until 9.5 days post coitum. Individuals in this developmental stage were optically mapped and compared according to their genotypes - homozygous non-mutant, heterozygote and homozygous mutant mouse embryos exhibited some degree of similarity, while other...

Heart disease including ischemic heart disease is the highest contributor to death and morbidity in the western world. The studies presented were conducted to determine possible pathways of protection of the heart against ischemia/reperfusion. We employed adenovirus mediated over-expression of Methionine sulfoxide reductase A (MsrA) in primary neonatal rat cardiac myocytes to determine the effect of this enzyme in protecting against hypoxia/reoxygenation. Cells transfected with MsrA encoding adenovirus and subjected to hypoxia/reoxygenation exhibited a 45% decrease in apoptosis as compared to controls. Likewise total cell death as determined by levels of Lactate Dehydrogenase (LDH) release was dramatically decreased by MsrA overexpression. The initial hypothesis that led to our testing sulindac was based on the fact that the S epimer of sulindac was a substrate for MsrA and that this compound might function as a catalytic anti-oxidant based on a reaction cycle that involved reductio n to sulindac sulfide followed by oxidation back to sulindac. To test this we examined the protective effect of sulindac in hypoxia re-oxygenation in both cardiac myocytes in culture and using a Langendorff model of myocardial ischemia. Using this model of myocardial ischemia we showed that pre-incubation of hearts with sulindac, or the S and R epimers of sulindac resulted in protection against cell death. We present several lines of evidence that the protective effect of sulindac is not dependent on the Msr enzyme system nor does it involve the well established role of sulindac as a Cyclooxygenase (COX) inhibitor. Numerous signaling pathways have been implicated in myocardial protective mechanisms, many of which require fluctuations in ROS levels as initiators or mediators. / Sulindac shows very good potential as a preconditioning agent that could induce tissue protection against oxidative damage.Blocking of preconditioning pathways by administration of the PKC blocker chelerythine abrogated the ischemic protection afforded by sulindac. Secondly, an end-effector of preconditioning, inducible nitric oxide synthase (iNOS),was found to be induced by greater than 5 fold after 48 h prior feeding sulindac. / by Ian Moench. / Thesis (Ph.D.)--Florida Atlantic University, 2008. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2008. Mode of access: World Wide Web.

Positive associations between short-term exposure to ambient particulate matter (PM) pollution and cardio-respiratory morbidity and mortality have been established in epidemiologic studies. However, scientific uncertainties remain regarding which PM constituents and sources are most harmful to the exposed population. While tentative evidence of positive links between certain PM constituents and sources with specific health outcomes exists, significant heterogeneity in study findings remains. The chemical composition and emission source of air pollution vary not only temporally, but also geographically. Thus, substantial research on these characteristics under different atmospheres (e.g., Asian atmosphere) is warranted to enhance our understanding of PM-related health effects. / In Hong Kong, air pollution levels often exceed the World Health Organization’s air quality guidelines, posing serious public health threat. Although two decades of active research have associated PM mass (weights) concentration in Hong Kong with elevated risk of daily mortality and emergency hospital admissions, individual chemical constituents and sources responsible for the adverse health effects associated with PM mass have rarely been examined. This thesis attempted to reduce the current scientific uncertainty by making use of the speciation data for PM with aerodynamic diameter ≤ 10 μm (PM₁₀) to examine the associations between chemical constituents and daily cardio-respiratory emergency hospital admissions in Hong Kong between 2001 and 2008. It also capitalized on Positive Matrix Factorization (PMF) source apportionment model to create an alternative measure of PM concentrations that quantified the relative contribution of PM₁₀ sources. This enabled the assessment of health risks associated with exposure to particle mixture from specific sources. / Time-series analyses conducted in this work showed evidence of positive links of emergency hospitalizations with multiple PM₁₀ constituents for various exposure lags examined. In multipollutant models adjusting for gaseous co-pollutants, three groups of constituents were significantly associated with increased risk of cause-specific hospitalizations. They included: combustion-related constituents (i.e., elemental carbon, organic matter, potassium ion, manganese, nitrate ion, arsenic, lead), sea salt-related constituents (i.e., sodium ion, chloride ion, magnesium), and constituents related to soil/road dust (i.e., aluminum, iron). Significant associations were most evident between November to April. PMF model identified eight PM₁₀ sources: 1) vehicle exhaust, 2) soil/road dust, 3) regional combustion, 4) residual oil, 5) fresh sea salt, 6) aged sea salt, 7) secondary nitrate, and 8) secondary sulfate. Health effect analysis demonstrated that all PM₁₀ sources, except fresh sea salt, were positively associated with emergency hospitalizations. Combustion-related sources were positively associated with risk of cardiovascular hospitalizations at shorter cumulative lags than with respiratory hospitalization. Sources that primarily generate coarser particles (i.e., soil/road dust and aged sea salt) were linked to respiratory hospitalizations at shorter cumulative lags than combustion sources that emit fine particles, which were associated with respiratory hospitalization at delayed cumulative lags. / This work may help prioritize future toxicological research on the biologic mechanisms linking PM pollution to cardio-respiratory health. It also stresses the importance of regulation and reduction of traffic and other combustion-related emissions, reconfiguration of urban environment to reduce personal exposure to traffic emissions, as well as establishment of a coordinated and robust regional-scale air quality management plan. Constituent- and source-based air quality standards and policy strategies should be considered, supplementary to standards for total PM mass (e.g., PM₁₀ and PM₂.₅), to effectively protect the population from air pollution mixture. For example, policy measures aiming at controlling anthropogenic sources of coarse particles (e.g., soil/road dust, precursor gases for atmospheric conversion of aged sea salt) should be advisable. / 以往流行病學研究已經建立大氣懸浮顆粒（PM）污染短期暴露和心血管﹑呼吸系統疾病的發病率以及死亡率之間的關聯，但仍然不能確定究竟那種PM化學成分和排放源對暴露人群最有害。初步證據已經顯示了個別PM化學成分和排放源與某些疾病的相關聯，但是，現今研究結果之間依然存在顯著差異。此外，顆粒污染物的化學成分和排放源會隨地理空間不同而變化，因此有必要在不同地域的大氣環境下（如亞洲）進行研究，從而提高我們對PM影響健康的認識。 / 香港的空氣質量常超過世界衛生組織規定的可接受空氣質量標準，空氣污染已經成為一個嚴重的公共衛生問題。香港二十年的空氣污染研究已顯示PM質量濃度會增加死亡率和緊急入院的風險，然而仍然缺乏PM化學成分和排放源對健康影響的研究。本港環境保護署擁有十多年連續測量的可吸入懸浮粒子（PM₁₀）成分數據，因此本論文利用這數據與公共衛生數據來填補這個學術空白。具體的，本論文探索香港2001年至2008年間的PM化學成分與期間每日心血管和呼吸系統緊急入院的關聯。本論文還利用正交矩陣因子分解法（PMF），即大氣顆粒物的源解析技術，進行顆粒源分離，已建立替代單元以分別代表PM₁₀不同排放源的相對貢獻建立一個替代措施量化PM₁₀的成分中不同來源相對的貢獻，最終評估暴露於特定來源的PM₁₀混合成分的健康風險。 / 本文中的時間序列分析研究結果表明緊急入院率與多個PM化學成分在不同的暴露滯後時間上均存在正關聯。本論文的多種污染物時間序列的模型對氣體的共污染性進行了控制，研究發現以下三种顆粒物對某些具體疾病的緊急入院風險有顯著增加︰燃燒有關的顆粒（即︰碳元素，有機物，鉀離子，錳，硝酸根離子，砷，鉛），與海鹽有關的顆粒（即︰鈉離子，氯離子，鎂），以及與土壤/道路粉塵有關的顆粒（即︰鋁，鐵），這種相關性在寒冷的季節更為明顯（即每年的11月至4月）。PMF鑑定了八個PM₁₀的排放源或排放組合，包括︰1）汽車排氣，2）土壤/道路粉塵，3）區域燃燒產物，4）渣油，5）鮮海鹽，6）陳海鹽，7）二次硝酸鹽，和8）二次硫酸鹽。分析發現，除鮮海鹽外，其他PM₁₀的排放源與緊急入院呈正關係。研究顯示與燃燒有關的排放源能增加即時因心血管疾病緊急入院的風險，而主要含有粗顆粒的排放源能增加即時呼吸系統疾病緊急入院的風險，且在作用時間上比燃燒排放源（主要含有細顆粒）的危害更快。 / 本論文所提供的研究成果有助於重新定位未來有關空氣污染與心肺健康的生物學機制毒理學研究方向。研究結果強調監管和降低交通以及其他有關燃燒排放的重要性，利用合理城市環境結構及配置來減少居民暴露交通空氣污染的風險，以及建立區域性的空氣質量管理計劃。此外，本研究還建議除了PM質量濃度（如PM₁₀和PM₂.₅）的空氣質量標準以外，針對PM化學成分和排放源的空氣質量標準也應加以考慮，以有效地保護居民免受空氣污染的危害，例如，應考慮有關粗顆粒（如土壤/道路麈和前驅氣體）的人為來源的政策措施。 / Pun, Chit. / Thesis Ph.D. Chinese University of Hong Kong 2014. / Includes bibliographical references (leaves 108-133). / Abstracts also in Chinese. / Title from PDF title page (viewed on 18, October, 2016). / Pun, Chit. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

Οι καρδιαγγειακές παθήσεις αποτελούν την κύρια αιτία θανάτου στις αναπτυγμένες χώρες. Η στένωση σε μία αρτηρία, είτε αυτή προκαλείται από μία πάθηση όπως το ανεύρυσμα, είτε προκαλείται από μία περίδεση, όπως στις περιπτώσεις των συγγενών καρδιοπαθειών, μπορεί να μεταβάλλει σε σημαντικό βαθμό τα χαρακτηριστικά της ροής του αίματος. Η μελέτη της φυσιολογικής παλλόμενης ροής μέσα από στένωση είναι ιδιαίτερα σημαντική για τη διάγνωση και αντιμετώπιση των αγγειακών νόσων. Το ιατρικό πρόβλημα το οποίο εξετάζουμε στην παρούσα εργασία, είναι η στένωση της πνευμονικής αρτηρίας από περίδεση. Η περίδεση γίνεται προφανώς για να μειωθεί η υψηλή αρτηριακή πίεση και τελικά η ροή του αίματος προς τους πνεύμονες. Πρόκειται για μία χειρουργική μέθοδο αντιμετώπισης συγγενών καρδιοπαθειών. Η περίδεση της πνευμονικής αρτηρίας (pulmonary artery banding - PAB) είτε με συμβατικό τρόπο, ή με την πλέον σύγχρονη μέθοδο μέσω της συσκευής FloWatchTM προκαλεί τη στένωσή της. Με τον συμβατικό τρόπο η στένωση μπορεί να θεωρηθεί αξονικά συμμετρική, ωστόσο με τη χρήση του FloWatchTM είναι μη αξονικά συμμετρική. Έχει αποδειχθεί ότι τόσο η αξονικά συμμετρική, όσο και η μη συμμετρική περίδεση δημιουργεί διαφόρου βαθμού ίνωση του τοιχώματος της πνευμονικής αρτηρίας. Η αναδόμηση της πνευμονικής αρτηρίας είναι πολύ ηπιότερη στην περίπτωση της περίδεσης με το FloWatchTM. Η διαφοροποίηση αυτή έγκειται κυρίως στο ότι η συμβατική περίδεση προκαλεί για συγκεκριμένη μείωση της διατομής ισχυρότερη μείωση της περιμέτρου της διατομής από εκείνης της περίδεσης με το FloWatchTM. Στην παρούσα εργασία γίνεται αναφορά και ανάλυση των διαφόρων περιπτώσεων ροής σε στενώσεις αρτηριών, των συγγενών καρδιοπαθειών και των τεχνικών περίδεσης της πνευμονικής αρτηρίας. Επιπρόσθετα, μελετήθηκαν και υπολογίστηκαν η μόνιμη και η παλλόμενη ροή σε αξονικά συμμετρική 25% στένωση προκαλούμενη από συμβατική περίδεση, καθώς και η μόνιμη και παλλόμενη ροή σε μη συμμετρική 25% στένωση της πνευμονικής αρτηρίας όπως προκαλείται από το FloWatchTM, μέσω των πακέτων Fluent και Gambit. Η υπολογιστική μελέτη του πεδίου ροής περιλαμβάνει την κατανομή ταχυτήτων, τον προσδιορισμό των περιοχών ανακυκλοφορίας, την κατανομή των πιέσεων και την σύγκριση των παραπάνω μεγεθών με τα αντίστοιχα αποτελέσματα της βιβλιογραφίας. Τέλος, με βάση τα αποτελέσματα γίνεται η σύγκριση των δύο μελετούμενων μεθόδων περίδεσης. Αριθμητικά ρεαλιστικά δεδομένα ελήφθησαν από την καρδιοχειρουργική κλινική του νοσοκομείου Παίδων «Αγία Σοφία». / Cardiovascular diseases are the leading cause of death in developed countries. A stenosis in an artery , caused either by a disease such as an aneurism or by a banding (such as in congenital diseases) can change the characteristics of the blood flow very seriously. The study of the physiological pulsatile flow through a stenosis is very important for the diagnosis and treatment of the arterial diseases. The medical problem which is examined in this study is pulmonary artery stenosis caused by a banding. The banding takes place to reduce the high arterial pressure and finally the blood flow from the heart to the lungs. It is a surgical method used for treatment of congenital heart diseases. The pulmonary artery banding either with the use of the conventional method or the most modern with the use of the FloWatchTM technology causes stenosis of the artery. With the conventional method, stenosis can be considered axially symmetrical while with the use of FloWatchTM it is asymmetrical. It has been proven that both the axially symmetrical and asymmetrical banding cause fibrosis of the pulmonary artery walls of different degrees. The reconstruction of the pulmonary artery is milder where there is banding with FloWatchTM. This differentiation is based mainly on the fact that the conventional banding causes, for a specific decrease of the cross-section, a decrease in the perimeter of the cross-section higher than that of banding with FloWatchTM. In this assignment there is a report of different cases of flow in arterial stenosis, in congenital heart diseases and pulmonary banding techniques. In addition what was studied and appreciated was the steady and pulsatile flow in axially symmetrical 25% stenosis caused by the conventional banding, as well as the steady and pulsatile flow in asymmetrical 25% stenosis of pulmonary artery caused by FloWatchTM with the use of Fluent and Gambit. The numerical study of flow distribution includes velocity distribution, designation of back flow area, distribution of pressure and comparison of these quantities with the results in bibliography. Finally, based on the results, there is a comparison of the two banding methods under study. The numerical realistic data were received from the cardio-surgical clinic of children’s hospital “Aghia Sophia”.

Ventricular dysfunction and dilated cardiomyopathy (DCM) develop among untreated HIV-infected people at much higher rates than among HIV-negative individuals, resulting in significant contributions to morbidity and mortality. Mechanisms underlying development of HIV-associated cardiomyopathy (HIVCM) are as yet poorly understood. The well-characterized simian immunodeficiency virus (SIV) model of HIV infection provides a unique context for HIVCM pathogenesis studies in that SIV-infected rhesus monkeys develop myocardial lesions and contractile dysfunction similar to those described in HIV-infected people, suggesting a shared disease mechanism. Lymphocytic myocarditis is a commonly reported finding in AIDS patients at autopsy and constitutes one of several conditions known to predispose to development of DCM, irrespective of HIV-infection status. As lymphocytic myocarditis also occurs with high frequency among SIV-infected rhesus monkeys, a retrospective analysis of rhesus monkey cardiac tissue collected at necropsy was performed to examine viral and cellular correlates of lymphocytic inflammation within myocardial tissue. One subpopulation of macrophages, which has been reported by other groups to be associated with an anti-inflammatory phenotype, was found to correlate inversely with lymphocytic infiltration and positively with numbers of virus infected cells, suggesting effects of an anti-inflammatory cytokine production profile. In contrast, the detrimental effects of inflammatory cytokines on myocardial structure and function are well-recognized and HIV infection in general is characterized by chronic immune activation and inflammatory cytokine dysregulation. To further investigate a role for myocardial cytokine production in development of HIVCM, a prospective study was conducted in which SIV-infected rhesus monkeys and uninfected controls were treated with recurrent administration of inactivated Mycobacterium aviumcomplex bacteria (MAC). SIV-infected, MAC-treated animals rapidly developed significant ventricular systolic dysfunction and chamber dilatation not seen in control groups, suggesting an exaggerated myocardial sensitivity to exogenous antigenic stimulation. Concurrent treatment with the TNFα antagonist etanercept completely abrogated development of these changes, strongly implicating a causative role for TNFα in evolution of the contractile dysfunction and chamber remodeling. Findings reported from the current studies suggest that characteristics of local myocardial macrophage populations and the myocardial tissue cytokine milieu may play more important roles than lymphocytic infiltration, cardiomyocyte damage, or viral proteins in the pathogenesis of HIVCM.

Timely management in pre-hospital emergency care enhances the chances of patients' survival or clinical outcomes of an Acute Coronary Syndrome (ACS). In Botswana nurses serve in the frontline of pre-hospital emergency services as the initial recipients of the emergency reports and situations. Knowledge of the patient's characteristics will assist the nurses as well as the family/others to understand the patient's responses during an ACS situation and therefore enable prompt patient assessment and facilitation of early access to appropriate care. Patient and family involvement in care during cardiac emergencies also influences the patient outcomes. This is a non-experimental, quantitative, exploratory and descriptive study, designed to explore and describe the characteristics of patients with the experience of an ACS, and the available resources during the pre-hospital phase of emergency care, with the aim of improving patients' clinical outcomes. The results indicated that optimal care by nurses is essential in the chain of care influencing patients' chances of surviving ACS. / Health Studies / M.A. (Health Studies)

A quantitative research design for a descriptive and contextual study to determine the critical care nurses knowledge and data preferences regarding the central venous and pulmonary artery catheters management and decision making after coronary arte.y bypass graft operations and the utmzation period of the pulmonary artery catheter after coronary artery bypass graft operations. The data was collected through a questionnaire completed by critical care nurses and retrospective analysis of patient records through a structured checklist. Data analysis indicated the following: critical care nurses have a knowledge deficit in the management of the central venous and pulmonary artery catheters and felt more competent and confident in the central venous measurements. The utilization period of the pulmonary artery catheter was 48% compared to the 100% of the central venous catheter. / Advanced Nursing Science / M.A. (Advanced Nursing Science)

As doenças cardiovasculares acompanham o homem desde os tempos antigos. Mas foi apenas na sociedade moderna que elas se transformaram na principal causa de mortalidade no mundo. A manutenção da saúde é eixo central para se garantir o direito à vida, definido como direito fundamental pela nossa Constituição. Assim, desenvolver uma ferramenta específica para o atendimento aos pacientes de maior risco para estas doenças contribui para que este direito fundamental seja garantido na prática. Além disso, as doenças cardiovasculares são responsáveis por impactos negativos na economia, tanto pelos custos de atendimento como pelo potencial em incapacitar uma parcela da população que está em idade produtiva. Dadas estas características vem sendo desenvolvidas estratégias de saúde pública para sua prevenção e atendimento precoce. Este estudo se propôs a criar e avaliar a eficiência de um escore para estratificação de pacientes em espera para atendimento ambulatorial eletivo de cardiologia, com vistas a identificar aqueles de maior risco. Foi aplicado num ambulatório de cardiologia do Hospital de Clinicas da UFPR, com resultados iniciais promissores. O resultado da aplicação mostrou excelente sensibilidade/especificidade em identificar os pacientes de alto risco para eventos cardiovasculares, que deveriam ter seu atendimento ambulatorial priorizado, reduzindo assim a possibilidade de eventos cardiovasculares futuros. Entretanto, para sua completa validação deve ser testado em um universo maior de pacientes. / Cardiovascular diseases follow the man since ancient times. But, it was only in modern society that they have become the main cause of mortality worldwide. Maintaining health is the central axis to guarantee the right to life, defined as fundamental right by Brazilian Constitution. So, to develop a specific tool for the patient care at higher risk related to these diseases contributes to guarantee this fundamental right in practice. In addition, cardiovascular diseases are responsible for negative impacts on the economy, by both service costs and the potential to disable a portion of the working age population. Due to these characteristics, public health strategies have been developed for its prevention and early treatment. This study aimed to create and evaluate the efficiency of a score for stratification of patients waiting for elective outpatient cardiology, for identifying those at greatest risk situation. The SPECC was applied in an outpatient cardiology at Hospital de Clinicas, UFPR, with promising initial results. Result of its application showed excellent sensitivity/specificity in identifying patients at high risk for cardiovascular events, for whom outpatient care should be prioritized, thus, reducing the possibility for future cardiovascular events. However, for a complete validation, it should be tested in a larger patient population.

As doenças cardiovasculares acompanham o homem desde os tempos antigos. Mas foi apenas na sociedade moderna que elas se transformaram na principal causa de mortalidade no mundo. A manutenção da saúde é eixo central para se garantir o direito à vida, definido como direito fundamental pela nossa Constituição. Assim, desenvolver uma ferramenta específica para o atendimento aos pacientes de maior risco para estas doenças contribui para que este direito fundamental seja garantido na prática. Além disso, as doenças cardiovasculares são responsáveis por impactos negativos na economia, tanto pelos custos de atendimento como pelo potencial em incapacitar uma parcela da população que está em idade produtiva. Dadas estas características vem sendo desenvolvidas estratégias de saúde pública para sua prevenção e atendimento precoce. Este estudo se propôs a criar e avaliar a eficiência de um escore para estratificação de pacientes em espera para atendimento ambulatorial eletivo de cardiologia, com vistas a identificar aqueles de maior risco. Foi aplicado num ambulatório de cardiologia do Hospital de Clinicas da UFPR, com resultados iniciais promissores. O resultado da aplicação mostrou excelente sensibilidade/especificidade em identificar os pacientes de alto risco para eventos cardiovasculares, que deveriam ter seu atendimento ambulatorial priorizado, reduzindo assim a possibilidade de eventos cardiovasculares futuros. Entretanto, para sua completa validação deve ser testado em um universo maior de pacientes. / Cardiovascular diseases follow the man since ancient times. But, it was only in modern society that they have become the main cause of mortality worldwide. Maintaining health is the central axis to guarantee the right to life, defined as fundamental right by Brazilian Constitution. So, to develop a specific tool for the patient care at higher risk related to these diseases contributes to guarantee this fundamental right in practice. In addition, cardiovascular diseases are responsible for negative impacts on the economy, by both service costs and the potential to disable a portion of the working age population. Due to these characteristics, public health strategies have been developed for its prevention and early treatment. This study aimed to create and evaluate the efficiency of a score for stratification of patients waiting for elective outpatient cardiology, for identifying those at greatest risk situation. The SPECC was applied in an outpatient cardiology at Hospital de Clinicas, UFPR, with promising initial results. Result of its application showed excellent sensitivity/specificity in identifying patients at high risk for cardiovascular events, for whom outpatient care should be prioritized, thus, reducing the possibility for future cardiovascular events. However, for a complete validation, it should be tested in a larger patient population.

Bien que la lutte contre le tabagisme passif se soit récemment accentuée, la fumée de tabac demeure un des principaux polluants atmosphériques d’intérieur. Le tabagisme passif génère des réactions cardiovasculaires néfastes qui, lors d’expositions répétées, augmentent le risque de mortalité cardiovasculaire. Le but des travaux réalisés a été de repenser la toxicité cardiovasculaire aiguë de la pollution de l’air par la fumée de tabac, en analysant plus particulièrement le rôle joué par la nicotine sur les déterminants endothéliaux et sympathiques du tonus vasculaire.<p>Nous avons tout d’abord caractérisé, chez des volontaires sains non-fumeurs, les réactions vasculaires provoquées par une heure d’inhalation passive de fumée de tabac ou de fumée non tabagique.1 Nos résultats démontrent que le tabagisme passif provoque une réflexion plus précoce de l’onde de pouls au niveau aortique ainsi qu’une perte de la capacité vasodilatatrice microvasculaire dépendante de l’endothélium. De plus, nous avons observé que ces réactions sont spécifiques à la fumée de tabac, et perdurent plusieurs dizaines de minutes après l’arrêt de l’exposition. Le stimulus nicotinique exerce un rôle prédominant dans les changements de réflexion d’onde de pouls. Cependant, l’interprétation du rôle joué par la nicotine dans la toxicité endothéliale du tabagisme passif est limitée in vivo par les effets de la nicotine sur d’autres déterminants du tonus vasculaire, tel que le système orthosympathique. <p>Nous avons dès lors spécifiquement comparé, à l’aide d’un modèle d’aorte isolée de rats, les effets d’extraits de fumée de tabac, de fumée non tabagique et de nicotine pure sur la fonction endothéliale et la production radicalaire.2 Chaque type de fumée a entraîné une augmentation similaire de la production radicalaire au sein des vaisseaux, mais seul l’extrait tabagique a altéré la relaxation vasculaire dépendante de l’endothélium. Dans les mêmes conditions, la nicotine pure a respecté l’intégrité fonctionnelle de l’endothélium, ce qui permet d’exclure son implication dans les effets délétères aigus du tabagisme passif sur l’endothélium vasculaire. <p>Nous avons ensuite déterminé, par des mesures directes du trafic nerveux autonome sur une population de volontaires sains non fumeurs, les effets directs de la nicotine sur le contrôle chémoréflexe périphérique du système orthosympathique.3 Nos résultats démontrent que des taux de nicotine similaires à ceux générés par une heure d’exposition au tabagisme passif augmentent la sensibilité d’une importante boucle réflexe participant à l’homéostasie du système nerveux autonome. <p>Enfin, malgré tous ces effets délétères de la nicotine observés chez le non-fumeur, nous avons établi que la perfusion myocardique du patient à risque coronaire élevé n’est toutefois pas altérée par une prise de nicotine sublinguale.4 <p>Les effets cardiovasculaires du tabagisme passif sont rapides, spécifiques, et réunissent des conditions de stimulation orthosympathique et de dysfonction endothéliale potentiellement néfastes pour la perfusion coronaire. Les effets sympathicomimétiques de la nicotine représentent l’axe prédominant de la toxicité cardiovasculaire aiguë du tabagisme passif. Toutefois, la nicotine pure n’altèrant pas la perfusion myocardique du patient à risque coronaire, son utilisation peut donc être encouragée dans l’aide au sevrage tabagique. <p> / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished