Turbulent blood flow is involved in the pathogenesis of several cardiovascular diseases. While it is known that turbulence is present in patients with obstructive disease in the major vessels, the magnitude and impact of turbulence in the normal heart and aorta is still relatively unexplored. Besides, existing analysis method of the blood flow is a labour intensive process and requires excessive amount of time. A method to automatically create hemodynamic atlases has been developed, using 4D Flow magnetic resonance imaging (MRI), a powerful tool to measure blood flow characteristics. The resulting atlases show the expected blood flow characteristics in the aorta for a group of similar subjects. Application of the method in healthy young and healthy old has shown significant differences in kinetic energy and turbulent kinetic energy in the aortic flow.

Cardiovascular diseases form one of the most dangerous events that affect human life. They are usually the result of high blood pressure. Thus controlling blood pressure within patient specific healthy limits is a goal that we must target. There are two control loops for blood haemostasis inside the body either long term or short term. Baroreceptors control the short term blood pressure regulation. They are nerve endings that exist in certain locations within the blood vessel walls and they report blood pressure into the brain and the central nervous system. However the basics of their function are not yet known. We propose here that the baroreceptors work by converting circumferential and axial pressure into a stress into their respective direction and they start to send nerve signals based on a threshold of strain energy of the location they are embedded in. Thus baroreceptors A fibre is highly likely to exist in the stiffer adventitia, while the media will contain C fibres. This explains the reason behind having identical fibres with different threshold. We were able to arrive to this solution by getting a relationship between stress–strain relationship for the whole wall and for the arterial vessels. These findings are quiet significant as they allow a method to identify different stress in the arterial wall layers using whole wall experimental data and also as they were able to differentiate between different fibres based on their locations inside the arterial wall. A complete modelling of the baroreceptors function might lead to the formation of biosynthetic material that could interact with the body on the cellular level, so as to give humans the mean to the control of short term blood regulation thus preventing hypertension and its accompanying diseases such as atherosclerosis.

Abstract Chlamydia pneumoniae is a common human pathogen worldwide, which causes both upper and lower respiratory tract infections. In addition, C. pneumoniae infections have been associated with atherosclerosis and other chronic diseases, and successful treatment and eradication of the organism from tissues would therefore be desirable. The purpose of this study was to assess the effects of C. pneumoniae inoculations on the development of chronic infection and atherosclerotic changes in normocholesterolemic, wild-type mice. We also aimed to elucidate the effects of antibiotic and other treatments on the eradication of chlamydia and on the reduction of the pathologic sequelae induced by these infections. Female C57BL/6J mice were fed either normal chow when assessing the effects of acute infection, or a diet supplemented with 0.2% cholesterol when evaluating the atherosclerotic changes. Primary or repeated inoculations with C. pneumoniae isolate K7 were given to the mice intranasally, and the effects of treatments with telithromycin, levofloxacin and erythromycin antimicrobial agents and with the phenolic compounds quercetin, luteolin and octyl gallate were evaluated. The following methods were used to measure infection and treatment effects and the presence of chlamydia in tissue: chlamydia culture, PCR and RT-PCR methods, histology of lung, heart and aortic tissue, serologic methods and measurements of aortic contractility responses. Repeated C. pneumoniae inoculations induced persistent chlamydial DNA and inflammation in lung tissue and development of mouse Hsp60 autoantibodies. Infection was shown to influence aortic endothelial function, and repeated inoculations significantly increased subendothelial lipid accumulation in the aortic sinus area. A flavonoid, luteolin, was shown to effectively decrease the chlamydial load and inflammatory reactions in lung tissue. All antimicrobial agents eradicated the presence of viable chlamydia effectively; however, PCR positivity persisted in lung tissue despite the treatments. Only immediate treatment after each inoculation was able to decrease aortic sinus lipid accumulation. In conclusion, these data support the role of C. pneumoniae in promoting atherosclerotic development via autoimmune responses and also via direct effects on aortic tissue. Conventional antimicrobial treatments may not effectively eradicate persistent infection, and further studies are warranted to seek for alternative treatment options.

L'aorte conduit le sang oxygéné aux organes et amortit l'onde pulsatile cardiaque. Au cours du vieillissement, elle est exposée à des altérations hémodynamiques et à une rigidité augmentée, elle-même associée à la mortalité.L'objectif de ma thèse est de proposer, à partir de l'IRM et des simulations, des indices non-invasifs de l'hémodynamique aortique locale, qui soient simples, rapides et complémentaires aux indices IRM de géométrie et de fonction aortiques établis.Un premier volet est consacré au développement et la personnalisation d'un modèle 1D de l'aorte descendante, validé qualitativement et quantitativement avec des données IRM sur 7 sujets, afin d'extraire des paramètres de pression, vitesse et surface.Un second volet, dédié aux données IRM, est centré sur :la comparaison de 7 méthodes d'évaluation de la pulsatilité aortique et leur validation avec la référence sur 70 sujets sainsla quantification du flux réverse aortique et l'étude de sa variation avec l'âge, ainsi que l'identification de ses déterminants sur 96 sujets sainsl'estimation automatique d'indices hémodynamiques de la sténose valvulaire aortique (SVA) et leur comparaison à l'échocardiographie Doppler sur 53 patients avec une SVA et 21 contrôles.Ainsi, le modèle aortique pourrait aider à identifier les déterminants des altérations aortiques et à consolider les observations in vivo. Par ailleurs, les outils mis au point pour l'analyse reproductible des données d'IRM fournissent des indices caractéristiques du vieillissement, qui pourraient être étudiés vis-à-vis des organes cibles (coeur, cerveau, rein, etc.) dans les pathologies cardiovasculaires (hypertension artérielle, drépanocytose). / The aorta conducts oxygenated blood to organs and also cushions the cardiac pulse wave. Such artery is exposed to age-related hemodynamic alterations and increased stiffness, which is associated with mortality. The objective of my PhD thesis is to propose, using MRI and numerical simulations, non-invasive indices of local aortic hemodynamics, which would be simple, fast and complementary to established aortic geometry and function MRI indices. A first work aims at developing and personalizing a 1D model of the descending aorta, as well as validating such model both qualitatively and quantitatively against MRI data acquired in 7 subjects, to eventually extract pressure, velocity and area parameters. A second work, which is based on MRI data, focuses on: the comparison of 7 methods for the evaluation of aortic pulsatility and their validation against the reference method in 70 healthy subjects, the quantification of aortic reverse flow and its variation with age, as well as the identification of its prime determinants in 96 healthy subjects, : the automated estimation of hemodynamic indices in aortic valve stenosis (AVS) as well as their comparison with the reference Doppler echocardiography, in 53 patients with AVS and 21 controls. Thus, the aortic model could help to identify determinants of aortic alterations and to strengthen in vivo observations. Besides, software tools developed for the reproducible analysis of MRI data provide indices that are characteristic of aging, and which could be studied in relation to end-target organs damage (heart, brain, kidney, etc.) in the setting of cardiovascular pathologies (hypertension, sickle cell disease).

Endothelial cells, EC, are the cell type closest to the blood stream in vessel walls. These cells can affect the origin of atherosclerosis, plaques clogging the vessels. The behaviour of EC is affected by neighbouring smooth muscle cells and shear stress from the blood flow. The aim with this thesis was to fabricate a structure for an aorta-on-a-chip that can be used to study these two parameters and their influence on EC and vascular diseases. Previous research using a two-channel system resulted in leakage and low viability of the muscle cells. A three-channel system has therefore been made to include a middle channel with the muscle cells incorporated in a gel. Cell medium is flowed in the outer channels to provide the cells with nutrition. The flow in the channel with EC has been calculated to correspond to the shear stress in an aorta. Membranes of polyethylene terephthalate and polycarbonate were used to divide the channels and both were shown to be compatible with EC. Different bonding procedures were investigated to manufacture leakage-free chips. In the study, adhesive bonding clogged the channels and the parameters for thermal bonding of COC, cyclic olefin copolymer, were not fully optimised. This made chemical bonding with layers of PDMS, polydimethylsiloxane, the best alternative. APTES, (3-Aminopropyl)triethoxysilane, treatment in addition to plasma treatment on the surfaces improved the bonding strength. Polycarbonate membranes got better results in the bonding tests than polyethylene terephthalate. The resulting aorta-on-a-chip was therefore successfully fabricated in PDMS and polycarbonate membranes using plasma and APTES treatment for bonding.

O pinçamento e o despinçamento da aorta abdominal infra-renal são procedimentos de rotina em ctrurgta vascular, sendo utilizados muitas vezes em pacientes portadores de aterosclerose difusa e sujeitos ao risco de complicações hemodinâmicas durante os eventos da abordagem desse segmento. O objetivo deste trabalho era analisar as alterações da pressão arterial média, pressão de oclusão da artéria pulmonar, resistência vascular sistêmica e índice cardíaco, antes e após o pinçamento e o despinçamento da aorta abdominal de suínos portadores e isentos de uma estenose acentuada implantada na aorta abdominal infra-renal, durante a cirurgia de substituição do segmento aórtico comprometido por uma prótese de politetrafluoretileno. Foram estudados 14 suínos de raça mista (White x Landrace) com idade próxima a 4 semanas, divididos em dois grupos. O grupo I era constituído de 6 animais e foi submetido à colocação de um anel sintético na aorta abdominal infra-renal, formando uma estenose acentuada. O grupo li era formado por 8 animais e foi utilizado como controle. Os animais foram submetidos à reintervenção 12 a 16 semanas após o procedimento através de laparotomia mediana sob anestesia geral. A aorta abdominal foi abordada e o pinçamento estabelecido em posição transversal infra-renal, permitindo a substituição do segmento estenosado por uma prótese de politetrafluoretileno As variáveis hemodinâmicas foram medidas através de um cateter de termodiluição 7F e cateteres inseridos no átrio direito e artéria carótida esquerda, conectados a um monitor de pressão adaptado a um computador de débito cardíaco. As medidas das variáveis foram realizadas 3 minutos antes e após o pinçamento e 3 minutos antes e após o despinçamento da aorta abdominal, associado a um período de isquemia de 25 minutos. Para a análise estatística, utilizou-se o teste de Mann - Whitney - Wilcoxon para a comparação entre os grupos e o teste de Friedmann para testar o efeito do tempo entre as variáveis do mesmo grupo. Os resultados obtidos nas quatro medidas não apresentaram diferenças significativas na comparação das variáveis entre os dois grupos, mas na análise individual de cada grupo, apenas a pressão arterial média e a resistência vascular sistêmica aumentaram significativamente ao final do período de isquemia (medida 3) no grupo de animais isentos de estenose da aorta abdominal (grupo II). É possível concluir-se que o pinçamento da aorta abdominal infra-renal promove repercussões hemodinâmicas significativas em suínos cuja via troncular comum aos membros inferiores encontra-se isenta de uma obstrução severa crônica. / The clamping and unclamping are routine procedures in vascular surgery and are frequently performed in patients with difuse atherosclerotic disease. The risk of hemodynamic complications is present in this population during these events. The purpose of this study is to assess the changes in mean arterial pressure, pulmonary wedge pressure, systemic vascular resistance and cardiac index in pigs with and without a severe abdominal aortic stenosis. Fourteen Landrace x White pigs were studied, 3 to 4 months old, and divided in two groups. Six animais were submitted to an abdominal aortic constriction and eight pigs were used as control. The abdominal aorta was clamped transversaly and the stenosed segment was substituted by a PTFE prothesis 12 to 16 weeks after the first surgery. The cardiac output were measured with a computer using a 7 French thermodiluition catheter. The central venous pressure and mean arterial pressure were measured through an right atrial and left carotid lines. Variables were collected 3 minutes before and after clamping and unclamping. Statitical analysis was performed with the Mann - Whitney - Wilcoxon test to compare the data between groups and the Friedmann test to analyze the reponse to different times in the same group. The results showed insignificant changes on data analysis between the groups. The mean arterial pressure and systemic vascular resistance raised significantly before the unclamping only in group caracterized by the unconstricted abdominal aorta. We conclude that significant hemodynamic changes can occur in pigs without severe abdominal aortic constriction undergoing infrarenal aortic clamping.

Les maladies cardiovasculaires représentent la première cause de mortalité dans le monde. L’hypertension artérielle et l’hypertrophie du ventricule gauche en constituent deux facteurs de risque souvent asymptomatiques. Dans ce contexte, la pression aortique s’impose comme un indicateur de la santé cardiovasculaire reflétant non seulement les propriétés biomécaniques des artères centrales mais aussi la post-charge ventriculaire. La mesure de ce paramètre hémodynamique est donc cruciale pour le diagnostic et la prise en charge thérapeutique. L’objectif de ce travail est d’estimer non-invasivement la pression aortique en couplant l’Imagerie par Résonance Magnétique Cardiovasculaire (IRM-CV) à la modélisation de l’écoulement sanguin. Nous avons ainsi opté pour un modèle biomécanique unidimensionnel (1D) réduit, prenant en compte l’interaction du sang avec la paroi élastique de l’aorte. Ce segment 1D est couplé en sortie à un modèle Windkessel, dit 0D, modélisant l’ensemble du réseau vasculaire en aval de l’aorte. Les paramètres locaux du modèle 1D ainsi que ses conditions aux limites (conditions d'entrée et paramètres du modèle 0D) sont déterminés à partir des données acquises non-invasivement par IRM-CV. Cela permettrait des prédictions 1D spécifiques à chaque sujet/patient. Nous avons évalué la validité du modèle sur des fantômes d’aorte saine et pathologique. Un banc expérimental compatible avec l’IRM a été mis en œuvre; il reproduit au mieux l’écoulement aortique in vivo. Des mesures de pression invasives ont été confrontées à celles prédites par le modèle 1D. Nous avons également évalué la sensibilité du modèle 1D aux paramètres d’entrée. / Cardiovascular (CV) diseases remain the most common cause of death worldwide. Hypertension and left ventricle hypertrophy are two major risk factors associated to such diseases. In this context, aortic blood pressure is considered as a biomarker of increased CV risk and, more generally, a CV health indicator. In fact, it encodes information about biomechanical properties of central elastic arteries and represents left ventricle afterload. Assessment of this hemodynamic parameter is thus crucial for CV disease diagnosis and for evaluating therapeutic benefits. The aim of this work is to non-invasively assess the aortic blood pressure by coupling CV Magnetic Resonance Imaging (CV-MRI) to blood flow modeling. We thus developed a reduced one-dimensional (1D) flow model taking into account the fluid-structure interaction. A Windkessel (or zero-dimensional (0D)) model describing the arterial tree downstream of the aorta was coupled to the 1D segment. Both 1D model parameters and boundary conditions (inlet condition and 0D model parameters) were non-invasively determined using CV-MRI data. This gives the opportunity of deriving subject- or patient-specific blood flow models. To validate our approach, we applied our model to both healthy and pathologic aorta phantoms. Each phantom was mounted in an experimental setup reproducing as well as possible in vivo aortic flow and compatible with the MRI environment. Invasive pressure recording was compared to predicted pressure waves. We also performed a sensitivity analysis of our reduced 1D model.

The thesis is focused on the intra-aortic balloon counterpulsation (IABP) from the perspective of nurses in the cardiac intensive care. It consists of two parts. Theoretical and empirical. The theoretical part will deal with the intra-aortic balloon counterpulsation, including basic anatomy of the heart and blood vessels, the principle of IABC, its indications, contraindications, technology IABC and specific nursing care of patients with established IABC. The empirical part is treated as quantitative research, which is used for the data collection method anonymous questionnaire. The aim of the thesis is to determine nurses' knowledge of IABC in the cardiac intensive care and subsequent drafting of guidance for postoperative cardiac surgery department KARIM University, Prague. In this section are also included important questions and answers from the perspective of the specified variables obtained from the questionnaire and subsequent actions arising in practice. Key words Counterpulsation, Cardiac cycle, Aorta, Heart, Nursing care

<div><div><div><p>The aorta has many complex features including valve and vessel wall geometry, blood flow, and wall composition. Diseases such as aortic aneurysms and aortic valve lesions affect vessel function and may even lead to rupture, which can be fatal. However, current clinical diagnoses of aortopathies mainly rely on simple parameters such as diameter and growth rate. To better understand aortopathies and ultimately improve patient diagnoses and treatments, it is important to investigate disease progression as well as the effect of vessel wall composition changes and hemodynamic forces on aortic biomechanics, such as strain and wall shear stress distribution. Preclinical research using small animals allows for disease progression to be studied while controlling outside factors. The next important step is to apply the methods used in the preclinical studies to human patient data. Both preclinical and clinical studies often focus on noninvasive, patient-specific methods for further characterizing the biomechanics of the aorta using advanced techniques such as 4D flow magnetic resonance imaging, 4D ultrasound, computational fluid dynamics (CFD), and fluid structure interaction (FSI) modeling. Yet the challenge of bridging these research techniques to a clinical setting remains. Factors such as financial costs, acquisition time, and ease of analysis must be considered. Therefore, the following document highlights two specific aims to extend our knowledge about the effects of aneurysms and aortic valve lesions. We will 1) characterize the regional effects of murine abdominal aortic aneurysms on strain over time, and 2) use CFD and FSI to simulate the hemodynamic effects on the thoracic aorta using both murine and human patient imaging data. Conducting research using clinically translatable methods of biomechanical characterization that consider the complexity of the aorta on a patient-specific basis will contribute to our understanding and lead to better patient outcomes.</p></div></div></div>

The molecular weight of the vasoactive intestinal peptide (VIP) receptor was assessed in bovine aorta, and rat liver, lung, and brain by covalent cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The receptor in all four tissues was found to be a single polypeptide of approximate Mr 54,000, contradicting previous claims for substantial heterogeneity in the molecular weight of this receptor. Guanine nucleotides inhibit cross-linking of 125I-VIP to its receptor, and cross-linking with ethylene glycolbis(succinimidylsuccinate) provides further evidence for complex formation between VIP, its receptor and a guanine nucleotide-binding regulatory protein (G-protein). The precise mechanism of receptor-G-protein coupling may differ between the aorta and other tissues.