The purpose of this project was to assess techniques which could be implemented in clinical cardiac MRI using a moderate gradient performance imaging system in order to aid in the assessment of myocardial function. Possible improvements in image contrast were assessed using four different magnetisation preparation schemes applied prior to MR image acquisition in order to aid in the delineation of myocardial borders, and therefore improve cardiac image assessment quality. The usefulness of several novel T2*-weighted acquisition techniques were assessed in clinical cardiac applications in order to indirectly assess myocardial perfusion. Four magnetisation preparation schemes were applied in order to attempt to improve image contrast in short axis gradient-echo cardiac MRI; T2, T1, Magnetisation Transfer Contrast (MTC), and Double Inversion (DI). The T2, and preparation schemes proved to be the most effective, showing an initial improvement in image contrast by approximately 100% and proving effective in improving image contrast over the entire imaging duration {550 ms through the cardiac cycle). The MTC preparation scheme showed a 50% improvement in image contrast, again being effective over the entire imaging duration. The DI preparation scheme proved useful in creating a black blood gradient-echo image but showed no improvement in contrast throughout the imaging duration (since the DI preparation technique is essentially a 'snapshot' technique). Recent developments in cardiac MRI have moved towards assessment of myocardial perfusion, using first-pass contrast-enhancement imaging. This approach requires assessment of a large enough volume of the heart to allow assessment of perfusion as well as retaining a high temporal resolution of 7 or 2 seconds, and therefore a more modem high performance imaging system. For moderate performance gradient MR systems an alternative method of assessing myocardial perfusion is therefore required. Several novel techniques to assess myocardial T2* values in order to indirectly infer myocardial perfusion are introduced. The use of an original multi-echo gradient-echo imaging sequence to acquire T2* pixel-maps was investigated in phantoms and compared with commercially available sequences in order to validate its use.

Background: Histone deacetylases (HDACs) play a critical role in modulating myocardial protection and cardiomyocyte survivals. However, Specific HDAC isoforms in mediating myocardial ischemia/reperfusion injury remain currently unknown. We used cardiomyocyte-specific overexpression of active HDAC4 to determine the functional role of activated HDAC4 in regulating myocardial ischemia and reperfusion in isovolumetric perfused hearts. Methods: In this study, we created myocyte-specific active HDAC4 transgenic mice to examine the functional role of active HDAC4 in mediating myocardial I/R injury. Ventricular function was determined in the isovolumetric heart, and infarct size was determined using tetrazolium chloride staining. Results: Myocyte-specific overexpressing activated HDAC4 in mice promoted myocardial I/R injury, as indicated by the increases in infarct size and reduction of ventricular functional recovery following I/R injury. Notably, active HDAC4 overexpression led to an increase in LC-3 and active caspase 3 and decrease in SOD-1 in myocardium. Delivery of chemical HDAC inhibitor attenuated the detrimental effects of active HDAC4 on I/R injury, revealing the pivotal role of active HDAC4 in response to myocardial I/R injury. Conclusions: Taken together, these findings are the first to define that activated HDAC4 as a crucial regulator for myocardial ischemia and reperfusion injury.

No description available.

Assessment of left ventricular (LV) function is one of the most common requests made to cardiac imaging services. This demand stems from a large body of evidence that shows abnormal LV systolic and, more recently, diastolic function has important prognostic and treatment related implications for patients with a wide range of cardiovascular diseases. The vast majority of information supporting the use of conventional measures of LV function, such as ejection fraction, originates from population studies and large clinical trials. However, the application of these measurements to individual patients is far less defined, especially when used for serial evaluation. Central to these concerns is the relative paucity of data surrounding the test-retest reliability of conventional measures in clinical settings. Newer measures of LV function have been developed over recent years, with several techniques becoming widely used in clinical practice (i.e. tissue Doppler imaging) and others remaining largely research tools (i.e. 3D echocardiography, tissue strain/strain rate). Possible benefits of new technologies include improved identification and early detection of myocardial disease, improved reliability for monitoring progression of disease, and the development of novel methods to assess response to therapy. Despite this potential, the application and clinical utility of these techniques above and beyond more conventional measures remains in many cases to be adequately characterized. This thesis addresses several of these issues: from variability of novel and conventional measures of LV function in clinical practice, to new applications of novel functional measures in clinical settings.

Orientador: Aparecido Antonio Camacho / Resumo: O objetivo do presente estudo foi investigar a função miocárdica pela técnica de ecocardiografia bidimensional speckle tracking (2D STE) em pacientes submetidos à procedimentos anestésico prolongado, com a intenção de se detectar possível disfunção sistólica. Inicialmente para se determinar o intervalo normal da função sistólica na espécie, foram utilizados 31 coelhos da raça Nova Zelândia, adultos, hígidos, machos, com peso médio de 4,0 ± 0,53 kg, nos quais foram obtidos os índices sistólicos radiais como, velocidade rotacional e radial, deslocamento rotacional e radial, strain radial e strain rate radial. Posteriormente, para investigação da função sistólica sob diferentes modalidades ventilatórias, 32 coelhos foram distribuídos, aleatoriamente, em quatro grupos de modalidades ventilatórias diferentes constituídos de 8 animais cada, denominados grupo ventilação ciclada à pressão (GP), grupo ventilação ciclada à pressão associada à PEEP (GPP), grupo ventilação mandatória intermitente sincronizada (GM) e grupo ventilação espontânea (GE). Em todos os grupos, os parâmetros foram mensurados 40 minutos após a indução anestésica (M0) e reavaliados a cada vinte minutos, durante duas horas ininterruptas (M1, M2, M3 e M4). Portanto, o resultado demonstrados na presente investigação cientifica revelam que nenhuma modalidade ventilatória estudada proporcionou um quadro de disfunção sistólica a luz da técnica 2D STE quando foram comparados em cada momento de avaliação anestésica. / Abstract: The aim of this thesis was to investigate the cardiac function of patients undergoing prolonged anesthesia with the use of a two-dimensional speckle tracking (2D STE) technique to detect systolic dysfunction in order to maintain safety during anesthetic procedure. The study was carried out in healthy rabbits because this species is widely used as a model of experimentation for both humans and other animal species. Initially, the normal range of left ventricular radial systolic function was measured, for this purpose, 31 healthy male adults New Zealand rabbits were used, with average weight of 4.0 ± 0.53 kg, from a specialized producer; radial systolic indices were obtained, such as rotational and radial speed, rotational and radial displacement, radial strain and strain rate. Subsequently, 32 rabbits were randomly assigned to four groups of different ventilatory modalities consisting of 8 animals each, referred to as pressure-cycling ventilation group (GP), pressure-cycling ventilatory group associated with PEEP (GPP), synchronized intermittent mandatory ventilation group (GM) and spontaneous ventilation group (GE). In all groups, the parameters were measured 40 minutes after anesthetic induction (M0) and reevaluated every twenty minutes, for two uninterrupted hours (M1, M2, M3 and M4). Therefore, the results demonstrated in the present scientific investigation reveal that no studied ventilatory modality provided a picture of systolic dysfunction in light of the 2D STE techni... (Complete abstract click electronic access below) / Doutor

No description available.

Le diabète est aujourd’hui la 7ème cause de mortalité dans le monde. Dans cette population, la cardiomyopathie diabétique est la principale cause de morbi-mortalité. Le développement de cette complication débutant dès l’apparition du diabète, un dépistage et une prise en charge précoces de cette pathologie sont donc de première importance et sont les deux objectifs visés par ces travaux. La première étude que nous avons réalisée a permis de démontrer l’utilité d’une évaluation compréhensive de la fonction régionale myocardique gauche par 2D speckle-tracking imaging, en conditions de stress à la dobutamine, dans le dépistage précoce de la cardiomyopathie diabétique chez des patients diabétiques de type 2 asymptomatiques. La deuxième partie de ces travaux a, quant à elle, donné lieu à deux études. L’étude clinique a permis de mettre en évidence une amélioration de la réponse au stress de la fonction régionale myocardique après 3 mois de supplémentation en vitamine D3 chez des patients carencés. L’étude expérimentale a, pour sa part, souligné les effets bénéfiques sur le remodelage et la fonction cardiaques de cette supplémentation, en prévention secondaire, dans un modèle murin de diabète de type 2 induit par un régime gras et sucré. Par ailleurs, cette étude a mis en lumière l’implication potentielle d’une modulation des taux myocardiques en espèces lipotoxiques par la vitamine D3 dans ces effets. L’ensemble de ces travaux de thèse a ainsi permis, d’une part, de proposer une technique de dépistage des signes précoces d’altération de la fonction cardiaque chez le patient diabétique de type 2 et, d’autre part, de montrer les effets bénéfiques d’une supplémentation en vitamine D3 dans ce contexte. / Diabetes has reached the 7th place in the world’s top ten mortality causes. In this population, morbi-mortality mainly originates from diabetic cardiomyopathy. This complication evolving from the onset of diabetes, early diagnosis and care are of paramount importance and are the two purposes of this work. In our first study, we demonstrated the relevance of a comprehensive 2D speckle-tracking imaging analysis, under dobutamine stress, in unmasking early left ventricular regional myocardial dysfunction in a population of asymptomatic type 2 diabetic patients. In the second part of this work, we performed two studies. In the first one, we brought to light an improvement of regional myocardial function response to dobutamine stress after a three-month vitamin D3 supplementation protocol, in deficient patients. The second study was performed in a mouse model of diet-induced type 2 diabetes. In this last work, we put forward the beneficial effects of vitamin D3 supplementation, in secondary prevention, on cardiac remodeling and function. These cardioprotective effects may be, at least in part, on account of modulatory effects of vitamin D3 on myocardial lipotoxic species levels. This whole work allow us to propose a tool enabling recognition of early cardiac function impairments in type 2 diabetic patients and to demonstrate the beneficial effects of vitamin D3 supplementation in this context.