Thesis (Ph.D.) - University of Queensland, 2005. / Includes bibliography.

There is growing interest in using large-scale observational data collected through national disease registries to develop clinical prediction models (CPMs) that use the experiences of past patients to make predictions about risks of outcome in future patients. CPMs are often developed in isolation across different populations, with repetitive de novo development a common modelling strategy. However, this fails to utilise all available information and does not respond to changes in health processes through time/space. Using the UK transcatheter aortic valve implantation (TAVI) registry as motivation, this thesis aimed to develop methods that improve the development of CPMs within local populations. Three research questions (RQs) were considered: (1) what are the challenges of mortality risk prediction in TAVI due to changes in procedure knowledge and the patient population? (2) Can we use a combination of baseline patient characteristics to predict the risk of mortality post TAVI? (3) How can we exploit multi-dimensional information about patients to inform clinical decision-making at a local-level? Chapter 2 demonstrates potential to simplify the procedure by removing pre-dilation of the aortic valve, thereby altering the underlying treatment pathway, and Chapter 3 shows that mortality rates from registries should be reported in the context of the underlying patient population. Despite Chapter 2 and 3 presenting potential challenges to TAVI risk prediction (RQ 1), CPMs are fundamental to support benchmarking/audit analyses. To this end, Chapter 4 found that the performance of existing TAVI CPMs was inadequate for use in UK patients. Through the discovery of new risk factors (e.g. frailty) in Chapter 5, the thesis derived a UK-TAVI CPM for audit analyses within the UK cohort (Chapter 6). While Chapters 4-6 present the classic framework of CPM development (RQ 2), this cannot overcome the challenges of mortality prediction in the TAVI setting (RQ 1) and is not suited to support local healthcare decision-making (RQ 3). Thus, Chapter 7 found that local model development could be supported through aggregating existing models rather than re-development. Existing methods of model aggregation were extended in Chapter 8 to allow prior research and new data to be utilised within the modelling strategy; application of the herein derived method to the UK TAVI registry indicated that it could facilitate the choice between model aggregation and de novo CPM derivation. Generally, this thesis has the potential to improve the implementation of CPMs within local populations by moving away from the iterative process of re-development. Practically, the thesis derived a UK-TAVI CPM for audit analyses, using classic and novel methodology.

Le traitement endovasculaire est devenu en deux décennies le traitement de première intention pour les DAB aiguës compliquées. Cependant, le traitement endovasculaire des DAB aiguës n’est pas optimal et comporte des limitations, tant au niveau proximal que distal, sources de complications précoces et tardives.Notre travail proposait d’évaluer des techniques endovasculaires novatrices permettant d’optimiser le traitement au niveau de la crosse et en distalité au niveau de l’aorte thoraco-abdominale.Nous avons créé un modèle de dissection de type B sur aorte humaine cadavérique extensif et reproductible, se rapprochant au plus près des conditions cliniques et permettant l’évaluation in vitro des dispositifs prothétiques conçus pour aorte humaine.Nous avons évalué sur ce modèle in vitro de DAB aiguë le stenting nu extensif de l’aorte disséquée qui permettait de réaccoler le flap intimal de dissection de manière expérimentale mais entrainait une sténose dans 54% des cas sur les artères viscérales naissant de l’aorte lorsque celles-ci naissaient du faux chenal. Ces artères pouvaient être cathétérisées à travers les mailles du stent.Nous avons ensuite évalué les résultats cliniques de cette technique, associé à un ballonnement du stent, dans le traitement des DAB aiguës compliquées avec un remodelage complet immédiat de l’aorte thoraco-abdominale stentée, persistant à moyen terme et permettant de limiter l’évolution anévrysmale à moyen terme.Enfin nous avons montré sur modèle in vitro la faisabilité et la précision au largage d’une endoprothèse avec échancrure proximale créée par le chirurgien pour avancer la zone d’ancrage dans la crosse, permettant un traitement endovasculaire exclusif en urgence des DAB aiguë compliquée avec un collet court ou une atteinte de la crosse aortique.Ces résultats offrent des perspectives d’évolutions du traitement des dissections aortique de type B au stade aigu, mais aussi plus largement des perspectives d’évolution pour le traitement des dissections de type A, des dissections chroniques, et plus généralement des pathologies de la crosse. / Thoracic endovascular aortic repair (TEVAR) is considered as the first line therapy for complicated acute type B aortic dissection (cABAD). However, current endovascular treatment has limitation regarding the proximal anchoring when aortic arch is involved and regarding the dissected aorta distally to the stent graft leading to early and late complication.The aim of this work was to assess new endovascular techniques to optimise endovascular treatment of ABAD in the aortic arch and in the thoraco-abdominal aorta.We reported the first model of ABAD in human cadaveric aorta, which was reproducible, extended to the infra-renal aorta and close to clinical pattern, allowing for human aortic devices assessment.We assess on this model extensive bare metal stenting of the dissected aorta, which was effective in true lumen reexpansion but induced a drop in pressure in the visceral arteries in 54% when they were supplied by the false lumen.Then, we assessed the results of this technique, associated with balloon inflation of the bare stent in clinical practice, which allowed an immediate and mid-term persisting complete remodelling of the stented thoraco-abdominal aorta, with a low dissecting aneurysmal evolution at one year of follow-up.Finally we reported a model of physician modified scalloped stent graft on currently available thoracic aortic device to extend the proximal landing zone in the arch while preserving the supra aortic trunks.These finding allow for potential improvement of endovascular treatment of ABAD but also of acute type A dissection, chronic dissection and some other acute aortic arch diseases.

OBJECTIVE: This study aims to corroborate recent research demonstrating that patients with low body mass indexes tend to have worse postoperative survival outcomes compared to normal BMI patients. It also intends to compare survival outcomes and postoperative complications in transcatheter and surgical aortic valve replacement patients to determine which procedure, TAVR or SAVR respectively, is better for this challenging low BMI patient population. METHODS: This is a retrospective, single-center study comparing patient data collected from 2000-2013 at New York Presbyterian Hospital/Columbia University Medical Center. Patients were dividing into three groups on the basis of BMI and aortic valve procedure: low BMI SAVR (BMI < 22 kg/m2; n = 148; 20.36%), normal BMI SAVR (22-25 kg/m2; n = 458; 63.00%), and low BMI TAVR (< 22 kg/m2; n = 121; 16.64%). There is a total of 606 SAVR patients and 121 TAVR patients. To corroborate recent research that low BMI patients tend to fare worse than normal BMI patients, an unadjusted comparison were used to compare baseline demographics and postoperative outcomes of 148 low BMI patients who underwent SAVR with 458 normal BMI patients who underwent isolated SAVR. These cohorts were then compared via a Kaplan-Meier survival analysis and the log-rank test for 30 days, 6 months, 1 year and 3 years survival outcomes. The 148 low BMI SAVR patients were then compared to 121 low BMI patients who underwent TAVR on baseline demographics and preoperative risk factors. The two cohorts were compared using the Kaplan-Meier analysis and postoperative complications were compared utilizing a multivariable logistic regression after adjustment for age, gender, BMI and STS Scores. RESULTS: The unadjusted analysis of the low BMI and normal BMI SAVR cohorts displayed similar patient demographics and preoperative risk factors. The normal BMI group demonstrated higher EF (55% vs. 51.5%; p = 0.002) and incidence of HLD (47.68% vs. 37.76%; p = 0.038). Conversely, the low BMI cohort had more females (61.49% vs.42.79%; p < 0.001) and individuals with a history of Afib (27.78% vs.16.96%; p = 0.004). As shown in the Kaplan Meier curve, the normal BMI SAVR patients exhibited superior 6 months, 1 year and 3 years survival rates and low BMI was shown to be a significant independent predictor of mortality (HR 2.56; 95% CI: 1.47 – 4.47; p = 0.0009 at 1 year). The two groups had similar postoperative outcomes, however, the low BMI cohort had longer overall hospital stays (8 vs. 6.5 days; p = 0.0003). The low BMI SAVR and TAVR patient cohorts varied significantly on most patient demographics and preoperative risk factors. The low BMI TAVR patients tend to be older (95.04% vs. 55.41% of patients > 75 years old) and had higher STS Scores (10.41 vs. 3.88; p < 0.0001). They also demonstrated significant increases in all the preoperative risk factors excluding DM and prior CVA. The SAVR patients had significantly longer overall hospital stays (8 vs. 6 days; p < 0.0001), more re-exploration for bleeding (5.41% vs. 0.85%; p = 0.0411) and more patients discharged to home (68.24% vs. 50.85%; p = 0.0039) while the TAVR patients demonstrated higher rates of GI bleed (3.39% vs. 0.00%; p = 0.0240) and new PPM (10.17% vs. 0.68%; p = 0.0004). The low BMI SAVR cohort demonstrated better survival rates at 1 year and 3 years and low BMI TAVR was determined to be a significant independent predictor of mortality (HR 0.51; 95% CI: 0.30 – 0.88; p = 0.0146 at 1 year). After controlling for specific covariates in the multivariate logistic regression analysis, the low BMI SAVR had 1.73 times longer ICU stays, 1.90 times longer hospital stays and the odds of being discharged home was 17% less than the TAVR group (p = 0.0005, <0.0001, 0.5665). CONCLUSION: Although the rates of postoperative complications are fairly similar, patients with low BMIs demonstrated worse survival outcomes when compared to the normal BMI SAVR patients. With the current analysis, low BMI TAVR patients had a significantly worse preoperative profile compared to the corresponding SAVR cohort which explains the worse survival and postoperative outcomes. Despite this, the multivariable analysis showed that the low BMI SAVR patients had longer ICU and hospital stays as well as fewer discharges to home. As this is an ongoing study, steps should be made to balance the preoperative profile such that the low BMI SAVR and TAVR groups are comparable prior to survival and postoperative assessment. However, at the current status, TAVR has proven itself to be the preferred treatment for low BMI patients. / 2018-07-13T00:00:00Z

Un substitut fiable est nécessaire après résection circonférentielle étendue de la trachée. La transplantation trachéale (TT) s’est heurtée à l’impossibilité d’une revascularisation directe et au rejet. Ayant démontré chez l’animal la faisabilité du remplacement trachéal (RT) par allogreffe aortique (AA) sans immunosuppression, nous avons conduit une étude clinique à partir de 2005. Six patients atteints de cancer étaient inclus (27% des cas de la littérature) ; actuellement 3 sont en vie et en rémission (suivi moyen 81 mois). Cependant, contrairement à l’animal, nous n’avons pas observé chez l’homme de régénération trachéale des greffons, probable conséquence de leur ischémie initiale. Pour résoudre ce problème, nous avons conduit 5 séries d’investigations sur modèle lagomorphe : Etude de l’efficacité de l’enveloppement fascial (EF) sur la néo angiogenèse de l’AA. EF appliqué à un greffon composite (AA entourée d’anneaux cartilagineux allogéniques). RT avec ce greffon.Quarante neuf lapins étaient donneurs et 74 étaient receveurs de sexe opposé. Il n’y avait pas d’immunosuppression. Lors des EF, les greffons étaient enveloppés dans un lambeau de fascia latéro-thoracique, puis implantés sous la peau. Lors des RT et TT en 2 temps, la résection de la trachée du receveur était suivie d’une rotation au cou du greffon enveloppé, qui était suturé à la trachée native. Lors des RT en 1 temps, le greffon était directement interposé après résection de la trachée du receveur. Les lapins ont été suivis jusqu’au décès ou sacrifiés. Les études microscopiques, la détection des chromosomes X et Y (FISH) et des cellules en apoptose (APOSTAIN) ont permis d’étudier la revascularisation, la viabilité et le rejet des greffons.L’EF de l’AA (n=19) a permis de construire un nouvel organe tubulé et revascularisé. La FISH a démontré la migration de cellules de l’hôte au sein de l’AA, et la persistance de cellules du donneur, témoignant d’une ischémie minimale après EF. Mais ce greffon n’avait pas la rigidité requise pour un RT.• L’EF du greffon composite (n=9) a permis de construire un substitut trachéal rigide, à la structure cartilagineuse préservée. • Après RT avec greffon composite (n=10) les lapins sont décédés d’obstruction de la voie aérienne. Sept greffons sur 10 avaient une rigidité satisfaisante par calcification des cartilages, mais tous présentaient des lésions ischémiques (résultats insuffisants pour une application clinique).• Après EF, les segments d’ATDC (n=13) étaient viables. L’infiltration inflammatoire était minime, sans lymphocyte. L’apoptose observée évoquait une réaction de rejet à minima.• Après TT par longs segments d’ATDC (n=7), 6 lapins sont décédés de sténose par prolifération endoluminale fibroblastique de J3 à J48. Après TT par segments courts (n=7), 3 lapins sont décédés et 4, sacrifiés de J33 à J220, présentaient une perméabilité et une morphologie normale du greffon. Tous les greffons, présentaient des signes de néo angiogenèse. L’infiltration inflammatoire était variable, sans lymphocyte. Les cartilages se calcifiaient, de 90% à 100% après 30 jours. Enfin, la régénération épithéliale était observée dès J20. [...] / After extended circumferential resection of the trachea, a reliable substitute is needed. Tracheal transplantation (TT) failed because of impossibility for direct revascularization, and rejection. On the other hand, our animal studies have demonstrated the feasibility of tracheal replacement (TR) with aortic allografts (AA). Since 2005, we performed this procedure in 6 cancer patients (accounting for 27% of cases in the available literature), and 3 are alive with no evidence of disease (mean follow-up: 81 months). The graft of patients did not display, however, cartilage regeneration as shown in animal models, possibly due to critical ischemia prior to neoangiogenesis. To solve this issue, investigations were conducted in rabbit models: • Study of the efficacy of the lateral thoracic fascial flap wrap (FW) for neoangiogenesis of AA. FW applied to a composite graft (AA with external cartilage-ring support). Staged TR using the composite graft.FW applied to segments of tracheal allograft, epithelium-denuded and cryopreserved to reduce immunologic reaction. Staged, and then direct TT using these tracheal segments.Forty-nine rabbits were used as donors and 74 sex-mismatched as recipients. No immunosuppressive therapy was given. During FW, grafts were wrapped using a lateral thoracic fascial flap, and then implanted under the skin of the chest wall. During staged TR or TT, tracheal resection was followed by rotation of the flap-wrapped graft to the neck, and anastomosis to the native trachea. During direct TT, the allograft segment was interposed between the stumps of the resected trachea.Rabbits were followed-up to death or sacrifice. Microscopic examination, FISH analysis for detection of both X and Y chromosomes, and detecting apoptotic cells (APOSTAIN), were used to study the morphology, revascularization, viability, and determine rejection. The FW applied to AA (n=19) ensured the construction of a novel well-vascularized tube-shaped organ. FISH analysis showed migration of recipient cells into the AA, and persistence of normal cells from the donor suggestive of minimal ischemia. This construct, however, did not show stiffness sufficient to ensure TR. • The 9 animals in which FW was applied to composite graft showed a rigid tracheal substitute with preserved histological structure of cartilages.• The 10 rabbits undergoing TR with this composite graft died of central airway obstruction. Despite severe ischemic lesions, satisfactory graft stiffness was shown in 7 out of 10 animals, due to cartilage calcifications. The results did not allow, however, the use of the construct in the clinical setting.• The 13 animals in which FW was applied to epithelium-denuded-cryopreserved tracheal segments maintained viability. The inflammatory reaction was minimal, with no lymphocytes. Apoptosis events were suggestive of minimal immunological response.• The results of TT using long segments of epithelium-denuded-cryopreserved allografts were disappointing, since 6 rabbits sustained a graft stenosis because of intraluminal fibroblastic proliferation. Of 7 rabbits undergoing TT with short segments, 4 were euthanized between 33 and 220 days. They showed patency and satisfactory strain abilities of their graft due to cartilage calcification deposits; and microscopically, neoangiogenesis, non-specific inflammatory infiltrate with no lymphocytes and satisfactory epithelial cell ingrowths from day 20 [...]

Intra-aortic balloonpump (IABP) counterpulsation therapy is a volume displacement device designed to provide partial assistance to the left ventricle of the heart. Critical care nurses are expected to manage IABP therapy. It is therefore important that the critical care nurse has the knowledge to manage IABP therapy in a safe and therapeutic manner. The question arises: does the critical care nurse have the knowledge to manage IABP therapy? The purpose of this research study is to explore and describe the knowledge of the critical care nurse regarding the management of IABP therapy. The design of this research study is a quantitative, descriptive and contextual study, in which a sample survey was performed, using a questionnaire (based on a literature study) under controlled conditions. The knowledge of the majority of critical care nurses tested was found to be insufficient. Safe management guidelines and in-service training have been proposed to improve the situation. / lntra-aortiese ballonpomp (IABP) teenpulsasie terapie is 'n volume verplasings apparaat, antwerp om gedeeltelike ondersteuning aan die linker ventrikel van die hart te bied. Kritiekesorgverpleegkundiges is verantwoordelik vir die hantering van rASP terapie. Die vraag ontstaan: beskik die kritiekesorgverpleegkundige oor voldoende kennis rakende die hantering van IABP terapie? Die doel van hierdie studie is om die kennis van kritiekesorgverpleegkundiges te ondersoek en te beskryf rakende die hantering van IABP terapie. Die resultate van hierdie navorsingstudie dui daarop dat die meerderheid kritiekesorgverpleegkundiges wat getoets was oor onvoldoende kennis beskik ten opsigte van IABP terapie. Formulering van riglyne en indiensopleiding is aanbeveel om hierdie situasie te verbeter. Die navorsingsontwerp is kwantitatief, beskrywend en kontekstueel van aard, waartydens 'n gerieflikheidsteekproeftrekking gedoen is, met gebruik van 'n vraelys (gebasseer op 'n literatuurstudie) onder gekontrolleerde toestande. / Health Studies / M.A. (Nursing Science)

Made available in DSpace on 2016-07-01T13:10:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-09-12. Added 1 bitstream(s) on 2016-07-01T13:14:12Z : No. of bitstreams: 1 000866809.pdf: 1747343 bytes, checksum: 1bd62536c1ab61130611dd2e937d842f (MD5) / Os mecanismos envolvidos na remodelação cardíaca por sobrecarga de volume e o momento que a hipertrofia excêntrica apresenta prejuízo da função cardíaca são pouco conhecidos. Objetivos: a) Comparar alterações morfofuncionais, celulares (hipertrofia) e intersticiais (fibrose) em diferentes momentos da evolução da insuficiência aórtica; b) Verificar quais dos seguintes mecanismos estão envolvidos na remodelação cardíaca induzida pela IAo e em qual momento esta alteração acontece: alteração na metaloprotease 2 (MMP2) e do inibidor tecidual de metaloprotease 1 (TIMP1), alterações dos RNAs mensageiros específicos para a codificação das proteínas envolvidas na homeostase do cálcio (Fosfolambam, Ryr e Serca2a), alterações da expressão de proteínas fosfolambam e Serca2a do trânsito de cálcio. Casuística e Métodos: Estudo experimental com 64 ratos Wistar machos, 32 animais submetidos à insuficiência aórtica aguda (grupo IAo) e 32 animais a procedimento simulado (grupo Controle). Todos os animais foram seguidos com 1, 4, 8 e 12 semanas através de ecocardiogramas seriados e, após eutanásia, foram analisada morfometria do tecido cardíaco, atividade da MMP2 e TIMP-1, expressão gênica por Reação em Cadeia da Polimerase em Tempo Real das proteínas do trânsito de cálcio, expressão das proteínas Serca2a e fosfolambam pela técnica Western Blot. A análise estatística foi efetuada pela ANOVA de dois fatores; o pós teste de Holm Sidak; teste t grupo a grupo; Anova de 1 via, complementada por Tukey; correção por Bonferroni; teste de correlação de Spearman e teste de correlação de Pearson. Em todos os casos, o nível de significância adotado foi p<0,05. Resultados: Observou-se, na primeira semana, que o peso do VE e a pressão diastólica foi maior no grupo IAo. Na quarta semana, MMP2, TIMP-1, iMVE e fração de colágeno foram maiores no grupo IAo. A área do miócito e DDVE foram maiores... / The mechanisms that are involved in cardiac remodeling by volume overload and the moment the eccentric hypertrophy has impaired cardiac function are largely unknown. Objectives: a) to compare morphological, cell (hypertrophy) and interstitial (fibrosis) changes at different times of the evolution of aortic regurgitation (AR); b) to analyze which of the following mechanisms are involved in cardiac remodeling induced by aortic failure and at what moment this change takes place: change in the metalloprotease 2 (MMP 2) and tissue inhibitor of metalloproteinase 1 (TIMP1); changes of messenger RNAs to code proteins involved in calcium homeostasis (phospholamban, Ryr and SERCA2a), changes in expression of phospholamban and SERCA2a in the calcium transit. Methods: Experimental study with 64 male Wistar rats, 32 animals submitted to acute aortic regurgitation (AR group) and 32 animals sham procedure (Sham group). All animals were followed with 1, 4, 8 and 12 weeks by serial echocardiography and after euthanasia, were analyzed morphometry of cardiac tissue, the activity of MMP2 and TIMP-1, gene expression by RT-PCR of calcium homeostasis protein, SERCA2a and phospholamban expression by Western Blotting. Statistical analysis was performed by two-way ANOVA; the Holm Sidak post test; t test group to group; Anova one way, complemented by Tukey; Bonferroni correction; Spearman correlation test and Pearson's correlation test. In all cases, the significance level was set at p <0.05. Results: In the first week it was observed that weight of the LV and diastolic blood pressure were higher in the AR group. In the fourth week, MMP 2, TIMP-1, and collagen fraction were higher in the AR group. The myocyte area and left ventricle diastolic diameter (LVDD) were higher in the AR group compared to the sham group, from the eighth week. At weeks 8 and 12, the wall thickness (WT) was higher in the AR group than the...

Orientador: Paula Schmidt Azevedo Gaiolla / Coorientador: Marcos Ferreira Minicucci / Banca: Meliza Goi Roscani / Banca: Bertha Furlan Polegato / Banca: Paula Felippe Martinez / Resumo: Os mecanismos envolvidos na remodelação cardíaca por sobrecarga de volume e o momento que a hipertrofia excêntrica apresenta prejuízo da função cardíaca são pouco conhecidos. Objetivos: a) Comparar alterações morfofuncionais, celulares (hipertrofia) e intersticiais (fibrose) em diferentes momentos da evolução da insuficiência aórtica; b) Verificar quais dos seguintes mecanismos estão envolvidos na remodelação cardíaca induzida pela IAo e em qual momento esta alteração acontece: alteração na metaloprotease 2 (MMP2) e do inibidor tecidual de metaloprotease 1 (TIMP1), alterações dos RNAs mensageiros específicos para a codificação das proteínas envolvidas na homeostase do cálcio (Fosfolambam, Ryr e Serca2a), alterações da expressão de proteínas fosfolambam e Serca2a do trânsito de cálcio. Casuística e Métodos: Estudo experimental com 64 ratos Wistar machos, 32 animais submetidos à insuficiência aórtica aguda (grupo IAo) e 32 animais a procedimento simulado (grupo Controle). Todos os animais foram seguidos com 1, 4, 8 e 12 semanas através de ecocardiogramas seriados e, após eutanásia, foram analisada morfometria do tecido cardíaco, atividade da MMP2 e TIMP-1, expressão gênica por Reação em Cadeia da Polimerase em Tempo Real das proteínas do trânsito de cálcio, expressão das proteínas Serca2a e fosfolambam pela técnica Western Blot. A análise estatística foi efetuada pela ANOVA de dois fatores; o pós teste de Holm Sidak; teste t grupo a grupo; Anova de 1 via, complementada por Tukey; correção por Bonferroni; teste de correlação de Spearman e teste de correlação de Pearson. Em todos os casos, o nível de significância adotado foi p<0,05. Resultados: Observou-se, na primeira semana, que o peso do VE e a pressão diastólica foi maior no grupo IAo. Na quarta semana, MMP2, TIMP-1, iMVE e fração de colágeno foram maiores no grupo IAo. A área do miócito e DDVE foram maiores... / Abstract: The mechanisms that are involved in cardiac remodeling by volume overload and the moment the eccentric hypertrophy has impaired cardiac function are largely unknown. Objectives: a) to compare morphological, cell (hypertrophy) and interstitial (fibrosis) changes at different times of the evolution of aortic regurgitation (AR); b) to analyze which of the following mechanisms are involved in cardiac remodeling induced by aortic failure and at what moment this change takes place: change in the metalloprotease 2 (MMP 2) and tissue inhibitor of metalloproteinase 1 (TIMP1); changes of messenger RNAs to code proteins involved in calcium homeostasis (phospholamban, Ryr and SERCA2a), changes in expression of phospholamban and SERCA2a in the calcium transit. Methods: Experimental study with 64 male Wistar rats, 32 animals submitted to acute aortic regurgitation (AR group) and 32 animals sham procedure (Sham group). All animals were followed with 1, 4, 8 and 12 weeks by serial echocardiography and after euthanasia, were analyzed morphometry of cardiac tissue, the activity of MMP2 and TIMP-1, gene expression by RT-PCR of calcium homeostasis protein, SERCA2a and phospholamban expression by Western Blotting. Statistical analysis was performed by two-way ANOVA; the Holm Sidak post test; t test group to group; Anova one way, complemented by Tukey; Bonferroni correction; Spearman correlation test and Pearson's correlation test. In all cases, the significance level was set at p <0.05. Results: In the first week it was observed that weight of the LV and diastolic blood pressure were higher in the AR group. In the fourth week, MMP 2, TIMP-1, and collagen fraction were higher in the AR group. The myocyte area and left ventricle diastolic diameter (LVDD) were higher in the AR group compared to the sham group, from the eighth week. At weeks 8 and 12, the wall thickness (WT) was higher in the AR group than the... / Doutor

Made available in DSpace on 2014-06-11T19:30:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-09-15Bitstream added on 2014-06-13T19:19:08Z : No. of bitstreams: 1 almeida_mj_dr_botfm.pdf: 527680 bytes, checksum: b40e49ce6cd134912d0e53aa6e29defc (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A migração da endoprótese é uma complicação do tratamento endovascular definida como deslocamento de sua ancoragem inicial. Para avaliação da migração verifica-se a posição da endoprótese em relação à determinada região anatômica. Considerando o aneurisma da aorta abdominal infra-renal, a área proximal de referência consiste na origem da artéria renal mais baixa e, na região distal, situa-se nas artérias ilíacas internas. Os pacientes deverão ser monitorizados por longos períodos a fim de serem identificadas migrações visto que estas ocorrem normalmente após 2 anos de implante. Para se evitarem migrações, forças mecânicas que propiciam fixação e determinadas por características dos dispositivos e a incorporação da endoprótese, devem predominar sobre forças gravitacional e hemodinâmica que tendem a arrastar a prótese no sentido caudal. Angulação, extensão e diâmetro do colo, além da medida transversa do saco aneurismático, são importantes aspectos morfológicos do aneurisma relacionados à migração. Com relação à técnica, o implante de endopróteses com sobredimensionamento excessivo (>30%) não é recomendado por provocar dilatação do colo do aneurisma, além de dobras e vazamentos proximais que também contribuem para migração. Por outro lado, endopróteses com mecanismos adicionais de fixação (ganchos, farpas e fixação supra-renal) parecem estar menos associadas às migrações. O processo de incorporação das endopróteses ocorre parcialmente e parece não ser suficiente para impedir migrações tardias. Neste sentido, estudos experimentais com endopróteses de maior porosidade e uso de substâncias que permitam maior fibroplasia e aderência da prótese à artéria vem sendo realizados e parecem ser promissores. Nesta revisão estes aspectos serão discutidos, em especial o uso da cola de fibrina. / Migration of the endoprosthesis is a complication of the endovascular treatment defined as misplacement of its initial fixation. In order to assess such migration, one shall verify the position of the endoprosthesis in relation to the determined anatomic site. Considering the aneurysm of the infra-renal abdominal aorta, the proximal area of reference consists on the origin of the lowest renal artery and, at the distal region, it is located next to the internal iliac arteries. Patients shall be monitored for long periods so that migrations can be spotted; these migrations usually occur 2 years after the implant. To avoid migration mechanical forces that enable fixation and that are determined by features of devices as well as the incorporation of the endoprosthesis have to predominate over gravitational and hemodynamic forces, which tend to drag the prosthesis toward to caudal direction. Angulation, extension and diameter of the neck, and transversal measure of the aneurysmatic sac, are important morphological aspects related to migration. In relation to technique, the implant of endoprosthesis with excessive oversizing (>30%) is not recommended because it leads to aortic neck dilatation, folds and proximal leaking witch contribute to its migration. On the other hand, endoprosthesis with additional fixation devices (hooks, barbs and supra-renal fixation) seem to be less associated with migration. The process of incorporation of the endoprosthesis occurs partially and does not seem to be enough to prevent later migrations. In this sense, experimental assessment with higher porosity endoprosthesis as well as the use of substances that allow higher fibroplasia and adherence of the prosthesis to the artery have been made and look promising. In this review, such aspects are discussed, specially the use of fibrin glue.

Orientador: Wilson Nadruz Júnior / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-22T22:15:29Z (GMT). No. of bitstreams: 1 Cipolli_JoseAlexandreAddeo_D.pdf: 1894085 bytes, checksum: feaa70799935fe151af270ee9d8ad0af (MD5) Previous issue date: 2013 / Resumo: A dilatação da raiz da aorta é observada mais frequentemente em indivíduos hipertensos e está associada de modo independente à hipertrofia do ventrículo esquerdo. Embora a estrutura do ventrículo esquerdo tenha determinantes gênero-específicos, ainda se desconhece a existência de diferenças ligadas ao sexo nos preditores do diâmetro da raiz da aorta em indivíduos portadores de hipertensão arterial. Nós avaliamos 438 pacientes hipertensos com hipertrofia do ventrículo esquerdo (266 mulheres e 172 homens) através de exame clínico, antropometria, parâmetros laboratoriais, hemodinâmicos e inflamatórios, exame de fundo de olho e ecocardiograma. Mulheres com dilatação da raiz da aorta tiveram maior débito cardíaco (p=0,0004), menor resistência vascular periférica (p=0,009), maior prevalência de regurgitação aórtica leve (p=0,02) e maior circunferência abdominal (p=0,04), enquanto homens com dilatação da raiz da aorta apresentaram maior prevalência de hipertrofia concêntrica do ventrículo esquerdo (p=0,0008), de regurgitação aórtica leve (p=0,005) e maiores níveis de Proteína C-reativa (p=0,02), quando comparados com sujeitos do mesmo sexo e sem dilatação da raiz da aorta. Entre as mulheres, a dilatação da raiz da aorta associou-se ao débito cardíaco, circunferência abdominal e regurgitação aórtica moderada, em um modelo de análise multivariada que incluía como variáveis independentes: idade, superfície corpórea, altura, índice de massa ventricular, HOMA (homeostasis model assessment), pressão arterial diastólica, menopausa e uso de anti-hipertensivos. Por outro lado, a dilatação da raiz da aorta associou-se a espessura relativa da parede do ventrículo esquerdo, Proteína C-reativa e regurgitação aórtica leve, sem contribuição de pressão arterial diastólica, altura, superfície corpórea, índice de massa ventricular, resistência vascular periférica e uso de anti-hipertensivos em homens. Em conjunto, esses resultados sugerem que a sobrecarga de volume e a obesidade central podem desempenhar um papel significativo na fisiopatogênese da dilatação da raiz da aorta nas mulheres hipertensas com hipertrofia de ventrículo esquerdo, enquanto o aumento da raiz da aorta nos homens hipertensos com hipertrofia de ventrículo esquerdo está mais associado a parâmetros inflamatórios e ao crescimento das células miocárdicas / Abstract: Aortic root (AoR) dilatation is more frequently observed in hypertensive individuals and is independently associated with left ventricular (LV) hypertrophy. Although the LV structure has sex-specific predictors, it remains unknown whether there are gender-related differences in the determinants of AoR size. We carried out a cross-sectional analysis of clinical, laboratory, anthropometric, funduscopic and echocardiographic features of 438 hypertensive patients with LV hypertrophy (266 women and 172 men). Women with enlarged AoR had higher cardiac output (P=0.0004), decreased peripheral vascular resistance (P=0.009), higher prevalence of mild aortic regurgitation (P=0.02) and increased waist circumference (P=0.04), whereas AoR-dilated men presented with a higher prevalence of concentric LV hypertrophy (P=0.0008) and mild aortic regurgitation (P=0.005) and increased log C-reactive protein levels (P=0.02), compared with sex-matched normal AoR subjects. In women, AoR dilatation associated with cardiac output, mild aortic regurgitation and waist circumference in a multivariate model including age, body surface area, height, homeostasis model assessment index, LV mass index, diastolic blood pressure, menopause status and use of antihypertensive medications as independent variables. Conversely, AoR dilatation associated with LV relative wall thickness, log C-reactive protein and mild aortic regurgitation without contributions from diastolic blood pressure, height, body surface area, LV mass index, peripheral vascular resistance and antihypertensive medications in men. Taken together, these results suggest that both volume overload and abdominal obesity are related to AoR dilatation in hypertensive women, whereas AoR enlargement is associated more with inflammatory and myocardial growth-related parameters in hypertensive men with LV hypertrophy / Doutorado / Clinica Medica / Doutor em Clínica Médica