Heart disease is a major cause of death in western countries. In order to diagnose and monitor heart disease, 3D echocardiography is an important tool, as it provides a fast, relatively low-cost, portable and harmless way of imaging the moving heart. Segmentation of cardiac walls is an indispensable method of obtaining quantitative measures of heart function. However segmentation of ultrasound images has its challenges: image quality is often relatively low and current segmentation methods are often not fast. It is desirable to make the segmentation technique as fast as possible, making quantitative heart function measures available at the time of recording. In this thesis, we test two state-of-the-art fast segmentation techniques to address this issue; furthermore, we develop a novel technique for finding the best segmentation propagation strategy between points of time in a cardiac image sequence. The first fast method is Graph Cuts (GC), an energy minimisation technique that represents the image as a graph. We test this method on static 3D echocardiography to segment the myocardium, varying the importance of the regulariser function. We look at edge measures, position constraints and tissue characterisation and find that GC is relatively fast and accurate. The second fast method is Random Forests (RFos), a discriminative classifier using binary decision trees, used in machine learning. To our knowledge, we are the first to test this method for myocardial segmentation on 2D and 3D static echocardiography. We investigate the number of trees, image features used, some internal parameters, and compare with intensity thresholding. We conclude that RFos are very fast and more accurate than GC segmentation. The static RFo method is subsequently applied to all time frames. We describe a novel optical flow based propagation technique that improves the static results by propagating the results from well-performing time frames to less-performing frames. We describe a learning algorithm that learns for each frame which propagation strategy is best. Furthermore, we look at the influence of the number of images and of the training set available per tree, and we compare against other methods that use motion information. Finally, we perform the same propagation learning method on the static GC results, concluding that the propagation method improves the static results in this case as well. We compare the dynamic GC results with the dynamic RFo results and find that RFos are more accurate and faster than GC.

The principal aim of this work is to test the viability of Blood Oxygenation Level Dependent (BOLD) measurements in human myocardium, an experiment which has seen promising attempts in recent literature. A central challenge to the ~uccess of these experiments has been in the limited scale of the measured effect; this work therefore includes efforts to separate the BOLD effect from noise and confounding signals. BOLD is then measured by intensity in MR images produced using Steady State Free Precession (SSFP) acquisition, weighted by a T2 preparation module to introduce the target contrast. Two modelling sections are included: first, the changes in physiology which influence the signal intensity in the MR images via the T2 dependence; and secondly the factors upon which the preparation depends, which are not entirely limited to the T2 of the tissue. These models are investigated with the aim of increasing the BOLD contrast and removing any other dependencies. An empirical model is shown to be suitable for the relationship between oxygenation and T2, and improvements are suggested and explained by thorough simulation ofthe preparation module. Compensation for a further confounding effect is also investigated: that of the increase in heart rate which accompanies the adenosine infusion used in the BOLD experiment protocol to reveal differences in the response of ischaemic and healthy tissue. The compensation is shown to reduce temporal variance in SI measurements, and to increase the separation between distributions of SI in tissue classes. A process of registration and segmentation is refined for sampling BOLD information from the SS FP images, and tested to show a low failure rate. Finally, the BOLD process is then tested in a set of human subjects including healthy volunteers and patients with coronary artery disease, investigating the consequent difference in tissue oxygenation. A significant difference is shown in the responses to stress of BOLD SI three tissue classes in these subjects.

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Title page, table of contents and summary only. The complete thesis in print form is available from the University of Adelaide Library. / The results presented in this thesis show the existence of TREK-1(Twik-RElated K+ channel; KCNK2), variant A and C of TREK-2 (KCNK10) and TRAAK (Twik-Related Arachidonic Acid-stimulated K+ channel; KCNK4) in human heart; the localization of TREK-1 and variants of TREK-2 on the membrane and in cytoplasmic areas of human cardiomyocyte; the notably high-level expression of TREK-1 in diseased human heart; the reverse expression of variant A and C of TREK-2 in normal and diseased human heart. These observations strongly indicate TREK channels play important roles in arrhythmia genesis and TREK-sensitive cardiac remodelling within the development of cardiac hypertrophy, ischemia cardiomyopathy and idiopathic dilated cardiomyopathy. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1248412 / Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2006

The tenn Acute Coronary Syndrome (ACS) encompasses a spectrum of patients who present with chest discomfort or other symptoms caused by myocardial ischemia or infarction. Since critical or acute care nurses care for such patients, they should have a thorough knowledge of ACS pathophysiology and current treatments for ACS The purpose of this research study is to explore and describe the knowledge level that the critical care nurses in a state hospital in East Texas feel they have regarding ACS. This study was quantitative, descriptive and contextual in design, in which a sample survey was performed, using a questionnaire based on a literature study. The response of most ofthe critical care nurses tested was that they felt they had insufficient knowledge. An in-service training session has been proposed to help improve the nurses' knowledge and expertise on ACS. / Health Studies / M.A. (Nursing Science)

Orientador: Heitor Moreno Junior / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-13T16:25:53Z (GMT). No. of bitstreams: 1 GazzotoFilho_Ademir_M.pdf: 876670 bytes, checksum: e7b954abb9a6ffd97c187bf6ceadaa8a (MD5) Previous issue date: 2009 / Resumo: O óxido nítrico (NO) é um mediador biológico que atua como molécula chave em muitos processos fisiopatológicos, como a regulação do tônus vascular, neurotransmissão, aprendizado, memória, dentre outros. Por causa de sua importância e envolvimento nos mecanismos fisiológicos e patológicos, a sua regulação e síntese têm sido extensivamente estudadas. A inibição crônica do NO por administração via oral do inibidor inespecífico da NO-sintase, a nitro-L-arginina metil éster (L-NAME) resulta em cardiopatia hipertensiva em ratos. A hipertensão renovascular [dois rins e um clipe (2R1C)] e o diabetes melito (DM) associadas, induzem a anormalidades morfológicas semelhantes às descritas no modelo de cardiomiopatia induzida por L-NAME em ratos, mas seus efeitos hemodinâmicos ainda são controversos. O presente estudo avaliou a função cardíaca e vascular nestes dois modelos de cardiomiopatia após oito semanas de tratamento. Foram utilizados ratos Wistar, divididos em 5 Grupos: Grupo Controle; Grupo L-NAME: 60mg/kg/dia de L-NAME; Grupo 2R1C: com estenose cirúrgica de artéria renal para indução de hipertensão arterial renovascular; Grupo DM: animais que receberam estreptozotocina (60 mg/kg intra-venoso), Grupo 2R1C+DM: animais submetidos à cirurgia para indução de hipertensão arterial renovascular e que receberam estreptozotocina. Foram avaliados os seguintes parâmetros: pressão arterial média (PAM), débito cardíaco (DC), resistência vascular periférica total (RVPT), dP/dt positivo e dP/dt negativo em coração isolado. Em todos os grupos foram encontrados aumento na PAM, RVPT e redução do DC depois de oito semanas em relação ao Grupo Controle. Os grupos L-NAME e 2R1C+DM apresentaram aumento na PAM (175,4±29,7 e 158,7±16,7 mmHg, respectivamente) e redução do DC após a oitava semana. A RVPT aumentou em ambos os grupos. Uma diminuição da dP/dt positiva foi observada no grupo 2R1C+DM (1895±98 mmHg/s, p<0,05) vs. Grupo Controle (2534±120 mmHg/s, p<0,05). A dP/dt negativa diminuiu nos grupos L-NAME e 2R1C+DM vs. Grupo Controle (1490±104 e 1460±94 mmHg/s, respectivamente vs. 2080±92 mmHg/s, p<0,05). O presente estudo demonstrou que, apesar das semelhanças morfológicas entre os grupos 2R1C+DM e L-NAME, este último não mimetiza as alterações hemodinâmicas dos modelos diabético-hipertenso renovascular associados em ratos. / Abstract: Nitric oxide (NO) is a biological mediator that acts as a key molecule in many pathophysiological processes such as regulation of vascular tone, neurotransmission, learning, memory, and others. Because of its importance and involvement in physiological and pathological mechanisms, its regulation and synthesis have been extensively studied. Inhibition of NO by chronic oral administration of the nonspecific inhibitor of NO-synthase, the nitro-L-arginine methyl ester (L-NAME) results in hypertensive cardiomyopathy in rats. The renovascular hypertension [two kidneys and clip (2K1C)] and diabetes mellitus (DM) associated induce morphological abnormalities similar to those described in the model of cardiomyopathy induced by L-NAME in rats, but its hemodynamic effects are still controversial. This study evaluated the cardiac and vascular function in these two models of cardiomyopathy after eight weeks of treatment. We evaluate the following parameters: mean arterial pressure (MAP), cardiac output (CO), total total peripheral vascular resistance (TPVR), positive and negative dP/dt in isolated heart. In all groups were observed increased MAP, TPVR and reduced DC after eight weeks in the control group. Wistar rats were divided into the following groups: Control; L-NAME: 60mg/kg/day; 2K1C+DM: streptozotocin (60 mg/kg) and one renal artery clipped. The following parameters were measured: mean arterial pressure (MAP), heart rate, cardiac output (CO) and total peripheral vascular resistance (TPVR). Positive and negative dP/dt was also evaluated in an isolated heart. L-NAME and 2K1C+DM groups had increased MAP (175.4±29.7 and 158.7±16.7 mmHg, respectively) and reduced CO after the 8th week. TPVR was increased in both groups. A decrease in positive dP/dt was found in the 2K1C+DM (1895±98 mmHg/s, p<0.05) vs. Control group (2534±120 mmHg/s, p< 0.05). Negative dP/dt was decreased in the L-NAME and 2K1C+DM groups vs. Control group (1490±104 and 1460±94 mmHg/s, respectively vs. 2080±92 mmHg/s, p<0.05). Decrease in positive dP/dt 2R1C+DM group compared to Control. The negative dP/dt decreased in L-NAME and 2R1C+DM groups. This study demonstrated that despite the morphological similarities between 2K1C+DM and LNAME groups; the L-NAME group did not mimics the hemodynamic changes in hypertension n-diabetic- renovascular model associated in rats. / Mestrado / Mestre em Farmacologia

The isolated perfused working heart was used to study hypertensive- diabetes induced alterations in cardiac function at 6 and 12 weeks after the induction of diabetes. There was no difference in cardiac function between normotensive Wistar and spontaneously hypertensive (SHR) diabetic rats at 6 weeks after diabetes induction. Wistar-Kyoto (WKY) rats were also included as normotensive controls in our 12-week study. Successful induction of diabetes was confirmed by the presence of hyperglycemia, hypoinsulinemia, glycosuria and increased haemoglobin glycosylation in all three diabetic groups. However, quantitation of various parameters of heart function revealed highly significant differences between SHR diabetic animals and all other groups, associated with an increased mortality. Serum lipids were elevated in SHR and Wistar and unaffected in WKY diabetic rats. Furthermore, thyroid hormone levels were not depressed in WKY diabetic rats and could explain the lack of cardiac dysfunction in these animals. The data provide further evidence that the combination of hypertension and diabetes mellitus produces greater myocardial dysfunction than is seen with either disease alone and is associated with a significant mortality. The effects of hydralazine on blood lipids, systolic pressure and cardiac performance were assessed in male Wistar rats, 6 weeks after they were made diabetic with streptozotocin (STZ). When hydralazine was administered for a 6-week period to the diabetic rats, their blood lipids were not significantly different from that of non-diabetic rats despite a low serum insulin. In contrast, blood lipids were elevated in the diabetic rats that were not treated with hydralazine; these animals also had low insulin levels. Cardiac performance was depressed in the untreated diabetic animals, but the cardiac performance of the hydralazine-treated diabetic animals showed a definite improvement which could be partly explained by their normal thyroid status in contrast to the untreated diabetic animals which were slightly hypothyroid. Blood pressure was elevated only in the untreated diabetic animals. Thus hydralazine controlled the high serum lipids and blood pressure and improved cardiac performance in STZ diabetic rats. To examine the influence of sex differences in the STZ model of diabetes, we studied left ventricular function in hearts from 6 week male and female rats. Significantly lower values for +dP/dt occurred in male diabetic rats compared with their own controls or female diabetics at most left atrial filling pressures. Decreases in this value for female diabetic rats compared to their own controls occurred only at high left atrial pressures. It appears that diabetes mellitus produces greater myocardial dysfunction in male diabetic rats. / Pharmaceutical Sciences, Faculty of / Graduate

Antibodies to tropomyosin, cardiac troponin I, myosin, and the beta-adrenergic receptors have been implicated in myocarditis, dilated cardiomyopathy, and heart failure. However, in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), there are only a few studies on how autoantibodies play a role in autoimmune mediated heart disease, despite the prevalence of these conditions. Ro52 antibodies have been implicated in fetal heart block, but their role in adult myocarditis remains elusive. In this study, we look beyond Ro52 and characterized the relevant autoantibodies in adult patients with SLE and RA myocarditis. An optimized immunoprecipitation followed by liquid chromatography mass spectrometry methodology was performed to determine putative auto-antigens in the human heart. The quantity and specificity of auto-antibodies was correlated with clinical measures of myocardial cellular infiltration, as determined by fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients with SLE and RA. We created autoantibody profiles that are complimentary to SLE and RA patients' clinical profile. Autoantibodies that correlated with cellular infiltration included TPI1, TPM1, MYL2, XRCC6 and APOA4. We then explored methodologies for testing patient autoantibodies using engineered cardiac tissues derived from human induced pluripotent stem cells (iPSCs). These tissues are increasingly used for drug discovery, pharmacology and in models of development and disease. While there are numerous platforms with engineered cardiac tissues, they often require expensive and non-conventional equipment and utilize complex video processing algorithms. As a result, only specialized academic labs have been able to harness this technology. In addition, methodologies and tissue features have been challenging to reproduce between different groups and models. Here, we describe a facile technology (milliPillar) that covers the entire pipeline required for studies of engineered cardiac tissues: (i) platform fabrication, (ii) cardiac tissue generation, (iii) electrical stimulation, (iv) automated real-time data acquisition, and (v) advanced video analyses. We validate these methodologies and demonstrate the versatility of the platform by showcasing the fabrication of tissues in different hydrogel materials and by using cardiomyocytes derived from different iPSC lines in combination with different types of stromal cells. We also validate the long-term culture (100 days) of tissues within the platform and provide protocols for automated analysis of force generation and calcium flux using both brightfield and fluorescent imaging. Lastly, we demonstrate the compatibility of the milliPillar platform with electromechanical stimulation to enhance cardiac tissue function. milliPillar tissues were cultured in the presence of patient autoantibodies to recapitulate the phenotype of myocardial disease, and the calcium transients and force generation were measured. Our results indicated that milliPillar tissues exhibited a decrease in force generation after 6 days in culture with SLE autoantibodies. Separately, our results indicated a prolonged calcium transient after 7 days in culture with SLE and RA autoantibodies. Changes to the downstroke of the calcium transient correlated most with patients’ autoantibody profiles and cellular infiltration. We confirmed autoantibody binding to live tissues/cells in 25% of the patients with SLE and myocarditis. Finally, we used changes in cardiac tissue function in the presence of autoantibodies to classify patients with SLE myocarditis with an accuracy of 87.5%.

Submitted in fulfillment of the requirements for the Degree of Masters in Technology: Cardiology, Durban University of Technology, 2012. / Cardiomyopathies and their resultant heart failure (HF) remain a major cause of cardiovascular morbidity and mortality (Wood and Picard, 2004). Idiopathic dilated cardiomyopathy (IDCMO) is a primary myocardial disease of unknown cause, characterized by left ventricular (LV) or biventricular dilatation and impaired myocardial contractility. Dilated cardiomyopathy (DCMO), along with rheumatic heart disease and hypertension (HPT), is one of the leading causes of HF in Africa. In fact, in an epidemiology study of 884 patients in Soweto, IDCMO was the second major cause of HF. Thirty five percent of patients in the study, with HF, had IDCMO (Sliwa, Damasceno, Mayosi, 2005). Methodology: Patients referred to the cardiomyopathy (CMO) clinic at Chris Hani Baragwanath hospital, situated in the echocardiographic lab, were recruited, provided they satisfied the exclusion and inclusion criteria and were enrolled after obtaining voluntary informed consent. From May 2009 to September 2010, 70 patients with IDCMO were recruited for this trial. Patients with DCMO were identified by means of echocardiographic criteria which included a left ventricular ejection fraction (LVEF) of less than 45% and an end diastolic dimension (EDD) of greater than of 52 mm (2D in long parasternal axis). Results: In the present study the prevalence of left ventricular (LV) thrombus in patients with IDCMO was 18.6%. When using Univariate logistic regression, the only independent predictors of LV thrombus formation was LVEF and age. However, when multivariate logistic regression analysis was applied to the data, the only predictor with a significant association was age. The reason for this is not clear. It is postulated that perhaps younger patients have differences in the pathophysiology of their disease such as a greater smoldering inflammatory component which may therefore predispose them to thrombus formation. For example the presence of IL-6 may be important in the formation of LV clot in cases of LV dysfunction (Sosin, Bhatia, Davis, Lip, 2003). The association between LVEF and LV thrombus was borderline significant. Conclusion: The prevalence of LV thrombus formation in this cohort of patients with IDCMO was 18.6%. Echocardiographic parameters alone cannot predict which patients are more likely to develop thrombus formation. / National Research Foundation