Orientador: Alfio Jose Tincani / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Mèdicas / Made available in DSpace on 2018-08-17T20:11:17Z (GMT). No. of bitstreams: 1 Servin_SilvioOscarNoguera_D.pdf: 954922 bytes, checksum: 98d734a92e137d605954e5dfefe3a20a (MD5) Previous issue date: 2011 / Resumo: Introdução: Pacientes que necessitam permanecer sob intubação endotraqueal por longos períodos ou que são submetidos à anestesia geral, poderão ter lesão na luz da traquéia devido a pressões exercidas pelo balonete terminal do tubo endotraqueal (TET). Em alguns casos, estas lesões no epitélio poderão evoluir para estenose ou ocasionalmente necrose. Objetivo: Apresentar um modelo de tubo endotraqueal modificado (TETM) em que a pressão do balonete é variável com o ciclo da ventilação mecânica, sendo o mesmo avaliado em simulador pulmonar e animal. Método: Em simulador pulmonar acoplado a ventilador mecânico (VM) ajustado para dois volumes correntes (VC) de 10 e 15 mL/Kg e complacência de 60 mL/cmH²0, foram utilizados dois modelos de tubos endotraqueais para avaliar a eficiência da ventilação do TETM. O primeiro, identificado como modificado (TETM), e o segundo como convencional (TETC) ambos de número 7,5 mm e 8,0 mm. Foi ainda realizado comparação entre os dois modelos de tubos em suinos da raça Large White sob anestesia geral e VM por período de 48 horas contínuas, sendo os animais posteriormente eutanasiados para análise histopatológica das traquéias. Resultados: Ambos TETM (7,5 e 8,0 mm) apresentaram escape de ar no simulador pulmonar. O menor escape (13%) foi observado no TETM de 7,5 mm com VC = 15 mL/Kg e o maior escape (32%) no TETM de 8,0 mm com VC = 10 mL/Kg. Apesar disto, ambos TETM apresentaram boa eficiência no simulador pulmonar. Na avaliação do uso dos TET em porcos, a análise histopatológica dos cortes seriados de suas traquéias foi observado que o TETM causou menos áreas traumáticas em seu epitélio tanto macro como microscopicamente, quando comparado com o TETC. Conclusão: O uso de novo modelo de TET poderá diminuir o risco da ocorrência de lesão traqueal sem prejuízo relevante para a mecânica respiratória / Abstract: Introduction: Patients who need to undergo endotracheal intubation for a long periods or who are under general anesthesia, may have damage in the trachea light due to pressure from the cuff end. In some cases, the lesions in the tracheal epithelium may progress to stenosis or occasionally necrosis. Objective: Show a modified endotracheal tube (TETM) in both a lung simulator and animals in which the cuff pressure is variable according to the mechanical ventilation cycle. Method: In a lung simulator coupled to a mechanical ventilator (MV) fitted with two tidal volumes (Vt) (10 and 15mL/Kg) and compliance of 60mL/cmH20, two types of endotracheal tubes were used: modified (TETM) and conventional (TETC) with numbers 7.5 and 8.0 in order to evaluate the efficiency of TETM ventilation. There was also a comparison between two pipe models in MV anesthetized pigs for a period of 48 hours after which the animals were put down and a histopathology of the tracheas was carried out. Results: Both TETMs (7.5 and 8.0) had air leaks in the lung simulator. The smallest air leak (13%) was observed at 7.5 with TETM VC = 15 mL / kg and the highest (32%) at 8.0 with TETM VC = 10 mL / kg. In spite of that, both TETM showed good efficiency at lung simulator. From histopathological evaluation, in serial sections of the animals' trachea, we observed that TETM caused less traumatic areas in their epithelium, both macro and microscopically, when compared to TETC. Conclusion: The use of this new TETM may decrease the risk of occurrence of tracheal injury without relevant damage in respiratory mechanics / Doutorado / Fisiopatologia Cirúrgica / Doutor em Ciências da Cirurgia

Stroke is ranked as the number one cause of death in Vietnam and the second leading cause of death in the world. Stenosis in the carotid arteries is one of the major risk factors for stroke, making it extremely important to confirm the diagnosis. Duplex ultrasound including measurements of the peak systolic velocity is considered the most accurate method when it comes to screening of carotid stenosis. However, the survey method is user dependent and differences in the results related to the scanning technique of the examiner may occur. The aim of this study was to determine the diagnostic variability for measuring peak systolic velocity in the common carotid artery in order to investigate whether the obtained results differ depending on the examiner. 30 healthy volunteers underwent carotid duplex ultrasound performed by two different examiners. Peak systolic velocity was measured with pulsed waved Doppler caudally of the carotid bifurcation. A T-test and a Bland-Altman plot were later applied in order to determine interobserver variability between the examiners. Results showed no significant difference in the measurements, with a mean difference of -0.01 m/s. Despite low interobserver variability, reliable conclusions cannot be drawn from the results since both examiners lacked adequate experience.

BACKGROUND Aortic stenosis affects not only the valve but also the myocardium. In response to the increased afterload, left ventricular hypertrophy initially occurs as a compensatory response to maintain wall stress and cardiac output but ultimately, decompensation and heart failure ensues. The transition from adaptation to decompensation is driven by myocyte death and myocardial fibrosis. The aims of the thesis are to investigate cardiovascular magnetic resonance assessment of disease severity and myocardial fibrosis, and explore its relationship with other biomarkers of disease activity and clinical outcome in patients with aortic stenosis. METHODS AND RESULTS The conventional assessment of aortic stenosis relies heavily on two-dimensional and Doppler echocardiography but there are inherent limitations in echocardiography that can affect the severity classification. I demonstrated that cardiovascular magnetic resonance offered a more accurate estimation of left ventricular volumes and mass, and excellent myocardial characterization. Indeed, inaccurate stroke volume estimation by Doppler echocardiography and inconsistent thresholds in current guidelines accounted for more than 40% of patients with discordant small-area, lowgradient aortic stenosis. These data may explain the variable prognosis reported in this unique group of patients, and argue for more accurate assessment of borderline cases with cardiovascular magnetic resonance. Late gadolinium enhancement imaging detects focal areas of established myocardial fibrosis. In many conditions, including aortic stenosis, a more diffuse form of fibrosis predominates, which is potentially reversible and not readily identified by late gadolinium enhancement. Recently several myocardial T1 mapping approaches have been developed to quantify diffuse fibrosis. Using a standardized and systematic approach, I compared several commonly used T1 mapping techniques and identified that extracellular volume had the best profile (reproducibility and discriminatory potential) for the identification of diffuse fibrosis in patients with aortic stenosis. Cardiac troponin is a structural protein present in the cardiac myocytes. Recent advances in assay technology have substantially improved sensitivity, allowing quantification of troponin concentrations with a high degree of precision in everyone. In more than 250 patients with aortic stenosis, I demonstrated that cardiac troponin I concentrations were independently associated with markers of left ventricular decompensation (hypertrophy and fibrosis) and predicted clinical outcome in patients with aortic stenosis. This suggests that myocardial fibrosis detected by cardiovascular magnetic resonance is consequent on myocardial injury secondary to left ventricular decompensation. Left ventricular hypertrophy with strain pattern on a 12-lead electrocardiogram is associated with poor outcome in patients with aortic stenosis, but the mechanism of this electrocardiographic pattern has not been described. In more than 300 patients with aortic stenosis, I demonstrated that these characteristic repolarization abnormalities were a highly specific marker of focal mid-wall myocardial fibrosis (specificity of 99% and sensitivity of 54%). Moreover, the prognostic value of this electrocardiographic pattern was again confirmed with markedly worse long-term outcomes in these patients. CONCLUSION I have demonstrated that cardiovascular magnetic resonance can assist in the assessment of disease severity in patients with aortic stenosis and discordant echocardiographic findings. Moreover, I have validated the assessment of diffuse myocardial fibrosis, as well as, demonstrated the close association between myocardial fibrosis and biomarkers of myocardial injury and electrocardiographic strain pattern that predicted an adverse outcome in patients with aortic stenosis.

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13421号 / 論医博第2229号 / 新制||医||1052(附属図書館) / (主査)教授 伊達 洋至, 教授 大鶴 繁, 教授 中山 健夫 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23607号 / 医博第4794号 / 新制||医||1055(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 溝脇 尚志, 教授 木村 剛, 教授 濵﨑 洋子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Objective: Aortic stenosis (AS) patients with eccentric hypertrophy (Ecc-LVH) have increased left ventricular (LV) size and possibly reduced ejection fraction (EF). However, previous studies suggest worse outcomes with concentric remodeling and hypertrophy. We hypothesized that Ecc-LVH pattern in AS patients will also be associated with greater heart failure (HF) and all-cause mortality (ACM). Methods: We queried the electronic medical record from a community-based university practice for all AS patients. We included patients with >60 days follow-up and interpretable Doppler echocardiograms. We recorded demographics, Doppler-echo parameters, laboratories, HF readmission and ACM with follow-up to 2083 days. There were 329 patients divided into 4 groups based on the presence of LV hypertrophy (LVH) and relative wall thickness (RWT) by echocardiography. Ecc-LVH had RWT<0.43 and LVH. Results: Patients with severe AS were older, had greater coronary disease prevalence, lower hemoglobin, greater LV mass index, more abnormal diastolic function, greater HF and ACM. Multivariate Cox proportional analysis revealed that valvulo-arterial impedance (p=0.017) and Ecc-LVH (p=0.033) were HF predictors. Brain natriuretic peptide>100 pg/ml (p<0.001) and Ecc-LVH (p=0.019) were ACM predictors. ACM was increased in Ecc-LVH patients with both moderate (HR=3.67-8.18 vs other geometries, p=0.007-0.0007) and severe AS (HR=3.94-9.48 vs normal and concentric remodeling, p=0.0002). In patients with HF, Ecc-LVH was associated with greater HF in moderate AS vs normal geometry (HR=3.28, p=0.0135) and concentric remodeling (HR=2.66, p=0.0472). Conclusions: Patients with AS and Ecc-LVH have greater ACM than other LV geometries with both moderate and severe AS and greater HF in moderate AS.

No description available.

Le rétrécissement aortique calcifié (RAC) est une maladie calcifiante de la valve aortique caractérisée par un remodelage fibro-calcique lentement progressif des feuillets valvulaires, et par un remodelage du ventricule gauche (VG). Il n’existe à ce jour aucun traitement pharmacologique capable de prévenir la maladie, et le seul traitement consiste en un remplacement valvulaire chirurgical ou percutané. Les objectifs de cette thèse étaient d’identifier des déterminants de la progression du RAC et du remodelage VG, d’étudier une nouvelle modalité d’évaluation de la sévérité du RAC, et d’analyser par une approche expérimentale les mécanismes initiateurs de la calcification valvulaire aortique. Les résultats de ce travail peuvent être résumés comme suit : - Le taux plasmatique de galectine-3 n’était pas associé au degré de sévérité du RAC ou au statut fonctionnel des patients. La galectine-3 n’avait pas de valeur pronostique sur la survenue d'événements liés au RAC. Les résultats observés sont en défaveur de l'utilisation de ce biomarqueur au cours de la prise en charge des patients ayant un RAC asymptomatique. - Dans une cohorte prospective de patients ayant un RAC au moins minime, le volume de graisse épicardique était indépendamment associé à un remodelage péjoratif du VG. Ce résultat suggère que la graisse épicardique pourrait être un déterminant du remodelage pathologique du VG via une interaction locale. - L’utilisation de l’imagerie de fusion a entrainé une augmentation du taux de discordance entre les paramètres de sévérité du RAC. Ce résultat était plus marqué chez les patients ayant une valve aortique bicuspide. Au regard de la classification et des seuils définissant actuellement la sévérité du RAC, et du fait de leur valeur pronostique bien démontrée, les résultats de cette étude sont en défaveur de l'utilisation de l’imagerie de fusion pour évaluer la sévérité du RAC. - L’accumulation dans le feuillet valvulaire aortique d’érythrocytes sénescents, suite à la survenue de lésions endothéliales non cicatrisées, constitue une situation délétère favorisant la différenciation des cellules valvulaires interstitielles vers un phénotype ostéoblastique et in fine le dépôt de calcium conduisant au RAC. La physiopathologie d’initiation des calcifications valvulaires et de progression du RAC est complexe et multifactorielle. La découverte de cibles thérapeutiques potentielles et l’optimisation de la prise en charge des patients ayant un RAC nécessite de combiner des études cliniques pour identifier les déterminants de la progression et de la réponse myocardique au cours du RAC, et une approche fondamentale pour caractériser les mécanismes impliqués dans la maladie. / Calcific aortic stenosis (AS) is characterized by a slowly progressive fibrocalcific remodeling of aortic valve leaflets, and by a left ventricular (LV) remodeling. There is currently no effective medical treatment capable of preventing disease progression, and the only treatment is surgical or percutaneous valve replacement. The objectives of this thesis were to identify determinants of AS progression and LV remodeling, to study a new modality of evaluation of AS severity, and to analyze through an experimental approach the initiating mechanisms of valve calcification. The results of this work can be summarized as follows: - The plasmatic level of galectin-3 was not associated with the degree of AS severity or the functional status of patients. Galectin-3 had no prognostic value for the occurrence of AS-related events. The results observed are not in favor of the use of this biomarker for the management of patients with asymptomatic AS. - In a prospective cohort of patients with at least mild AS, epicardial fat volume was independently associated with an adverse remodeling of the LV. This result suggests that epicardial fat may be a determinant of pathological LV remodeling through a local interaction. - The use of fusion imaging increased the rate of discordant AS severity parameters. This result was more pronounced in patients with a bicuspid aortic valve. Considering current classification and thresholds defining AS severity, and their well-proven prognostic value, the results of this study do not favor the use of fusion imaging to assess AS severity. - The accumulation of senescent erythrocytes in aortic valve leaflets, consecutive to unhealed endothelial injury, is a noxious condition that promotes the differentiation of valvular interstitial cells towards an osteoblastic phenotype and favor calcium deposition leading to AS. The pathophysiology of initiation of valvular calcification and AS progression is complex and multifactorial. The discovery of potential therapeutic targets and the optimization of the management of patients with AS require the combination of clinical studies to identify the determinants of AS progression and myocardial response, and a fundamental approach to characterize mechanisms involved in the disease.

Indiana University-Purdue University Indianapolis (IUPUI) / While computed tomographic angiography (CTA) has emerged as a powerful noninvasive option that allows for direct visualization of arterial stenosis(AS), it cant assess the hemodynamic abnormality caused by an AS. Alternatively, trans-stenotic pressure gradient (TSPG) and fractional flow reserve (FFR) are well-validated hemodynamic indices to assess the ischemic severity of an AS. However, they have significant restriction in practice due to invasiveness and high cost. To fill the gap, a new computational modality, called InVascular has been developed for non-invasive quantification TSPG and/or FFR based on patient's CTA, aiming to quantify the hemodynamic abnormality of the stenosis and help to assess the therapeutic/surgical benefits of treatment for the patient. Such a new capability gives rise to a potential of computation aided diagnostics and therapeutics in a patient-specific environment for ASs, which is expected to contribute to precision planning for cardiovascular disease treatment. InVascular integrates a computational modeling of diseases arteries based on CTA and Doppler ultrasonography data, with cutting-edge Graphic Processing Unit (GPU) parallel-computing technology. Revolutionary fast computing speed enables noninvasive quantification of TSPG and/or FFR for an AS within a clinic permissible time frame. In this work, we focus on the implementation of inlet and outlet boundary condition (BC) based on physiological image date and and 3-element Windkessel model as well as lumped parameter network in volumetric lattice Boltzmann method. The application study in real human coronary and renal arterial system demonstrates the reliability of the in vivo pressure quantification through the comparisons of pressure waves between noninvasive computational and invasive measurement. In addition, parametrization of worsening renal arterial stenosis (RAS) and coronary arterial stenosis (CAS) characterized by volumetric lumen reduction (S) enables establishing the correlation between TSPG/FFR and S, from which the ischemic severity of the AS (mild, moderate, or severe) can be identified. In this study, we quantify TSPG and/or FFR for five patient cases with visualized stenosis in coronary and renal arteries and compare the non-invasive computational results with invasive measurement through catheterization. The ischemic severity of each AS is predicted. The results of this study demonstrate the reliability and clinical applicability of InVascular.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20231号 / 医博第4190号 / 新制||医||1019(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 湊谷 謙司, 教授 山下 潤, 教授 川村 孝 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM