Background: Coronary heart disease can have a long lasting impact on affected individuals in terms of both physical and psychological adjustment and quality of life. It is, therefore, important to investigate determinants of outcome in these patients. The thesis has four main aims; (i) to investigate predictors of outcome (adherence, quality of life, functional impairment, psychological distress and benefit finding) post-myocardial infarction (MI); (ii) to determine the prevalence and stability of Type D personality in the UK; (iii) to determine if personality predicts outcome after controlling for mood, demographic and clinical factors, and (iv) to investigate potential mechanisms which may explain the link between personality and poor prognosis in cardiac patients. Method: Five studies were conducted. In Studies 1-3, participants completed measures of Type D personality, health-related behaviour, social support and neuroticism. In Study 4, participants completed an experimental stressor with cardiovascular monitoring. Study 5 was a prospective study in which 131 MI patients completed measures of personality, illness cognitions and outcome at two time points, 3-5 days post-MI, then again 3 months later. Results: The prevalence of Type D personality in the UK is 39% in the healthy population, and 34% in the cardiac population. In addition, Type D is predictive of adherence, quality of life, and functional impairment in post-MI patients after controlling for mood, demographics, and clinical factors. Five possible mechanisms (health-related behaviour, adherence, social support, cardiovascular reactivity, and illness perceptions) by which Type D may lead to adverse outcome in cardiac patients were identified. Mood predicted quality of life and functional impairment post-MI, illness perceptions predicted quality of life post-MI, and future thinking predicted quality of life, functional impairment and depression post-MI. Discussion: These findings have important therapeutic and theoretical implications for understanding the role of personality and illness cognitions in the short-term recovery of post-MI patients.

No description available.

The common human GNB3 825C > T variant, which is present in 50% of the world’s chromosomes, has previously been shown to predispose individuals to hypertension, cardiac and neural disorders. This variant causes the production of a stable and gain of function protein Gβ_3S- This thesis describes the discovery of a novel D153del mutation that produces an unstable, loss of function, protein Gβ_3D in the recessively inherited, retinopathy globe enlarged (rge) chickens. This thesis also demonstrates that the normal Gβ₃ downstream phosphorylation signalling pathways are significantly altered in a tissue specific manner in rge chicken organs and in a human GNB3 825TT lymphoblast cell line. In rge tissues expressing Gβ_3D protein, the cAMP induced GRK2 phosphorylation activity is significantly altered. Moreover MAPK1 (ERK2) phosphorylation is significantly decreased compared to normal tissues. In contrast human 825TT cell lines expressing the Gβ_3S protein, showed enhanced cAMP induced GRK2 and MAPK (ERK1 and ERK2) phosphorylation activity. These results confirm previous findings of 825C > T Gβ₃ studies, that Gβ_3S is indeed a hyper-activating structural variant, in contrast to the D153del Gp3D is a classical recessively inherited non-functional mutation.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Durante o tratamento radioterápico para tumores localizados na região torácica, parte do coração frequentemente é incluída no campo de tratamento e pode receber doses de radiação ionizante, significativas em relação à terapêutica. A irradiação do coração é capaz de causar importantes complicações cardíacas ao paciente, caracterizadas por alterações funcionais progressivas cerca de 10 a 20 anos após a exposição do órgão. Devido ao seu alto grau de contração e grande consumo energético, o tecido cardíaco é altamente dependente do metabolismo oxidativo que ocorre nas mitocôndrias. Danos as estas organelas podem levar ao decréscimo da produção de energia, tendo um impacto direto sobre a performance cardíaca. Ainda, ao interagir com as células, a radiação ionizante pode gerar uma série de eventos bioquímicos que conduzem a uma resposta celular complexa, em que muitas proteínas parecem estar envolvidas. Tendo em vista tais conhecimentos, o objetivo do estudo foi avaliar o aspecto ultraestrutural do tecido cardíaco, a bioenergética mitocondrial e a expressão diferencial de proteínas após irradiação. Os ensaios foram realizados em amostras de tecido cardíaco de ratos Wistar irradiados com dose única de 20 Gy direcionada ao coração. As análise tiveram início 4 e 32 semanas após irradiação. A análise ultraestrutural foi realizada através de microscopia eletrônica de transmissão. A respiração mitocondrial foi mensurada em oxígrafo, a partir das taxas de consumo de oxigênio pelas fibras cardíacas. A identificação de proteínas diferencialmente expressas foi investigada através de duas técnicas proteômicas: 2D-DIGE (2-D Fluorescence Difference Gel Electrophoresis) e uma abordagem label-free seguida de espectrometria de massas. Os resultados mostraram que os efeitos tardios da radiação incluem a degeneração das mitocôndrias e das unidades contráteis do tecido cardíaco, disfunções na cadeia respiratória mitocondrial e expressão diferencial de proteínas envolvidas no metabolismo energético de carboidratos, lipídeos e da fosfocreatina. De forma geral, o estudo mostrou que a irradiação cardíaca prejudica o processo de síntese energética, conduzindo a um déficit da taxa respiratória mitocondrial como efeito tardio. Tal evento pode culminar em disfunções mecânicas no coração, caracterizando o desenvolvimento de doenças cardíacas radioinduzidas. / During radiotherapy for tumors located at toracic region, part of the heart is often included in the treatment field and may receive a significant ionizing radiation dose comparing to the therapeutics. Heart irradiation is able to cause substantial cardiac complications to patient, characterized by functional progressive changes from 10 to 20 years after the exposure of the organ. Because of its high level of contraction and large energetic consumption, cardiac tissue is highly depending on oxidative metabolism which happens at mitochondrias. Damage to these organelles can lead to decreased energy production, having a direct impact on cardiac performance. Even when interacting with cells, ionizing radiation can generate a series of biochemical events that lead to a complex cellular response, in many proteins seem to be involved. Given this knowledge, the aim of the study was to evaluate the ultrastructural appearance of cardiac tissue, mitochondrial bioenergetics and differential expression of proteins after irradiation. The tests were performed on samples of cardiac tissue of rats irradiated with single dose of 20 Gy directed to the heart. The analysis started 4 to 32 weeks after irradiation. The ultrastructural analysis was performed by transmission electron microscopy. Mitochondrial respiration was measured in oxigraph from rates of oxygen consumption by cardiac fibers. The identification of differentially expressed proteins was investigated using two proteomic techniques: 2D-DIGE (2-D Fluorescence Difference Gel Electrophoresis) and a label-free approach followed by mass spectrometry. The results showed that the late effects of radiation include degeneration of mitochondria and contractile units of cardiac tissue, dysfunction in the mitochondrial respiratory chain and differential expression of proteins involved in energy metabolism of carbohydrates, lipids and phosphocreatine. In general, the study showed that the cardiac irradiation damages the process of synthesis energy, leading to a deficit in mitochondrial respiratory rate as late effect. Such event may result in mechanical dysfunction in the heart, characterizing the development of radiation-induced heart disease.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Durante o tratamento radioterápico para tumores localizados na região torácica, parte do coração frequentemente é incluída no campo de tratamento e pode receber doses de radiação ionizante, significativas em relação à terapêutica. A irradiação do coração é capaz de causar importantes complicações cardíacas ao paciente, caracterizadas por alterações funcionais progressivas cerca de 10 a 20 anos após a exposição do órgão. Devido ao seu alto grau de contração e grande consumo energético, o tecido cardíaco é altamente dependente do metabolismo oxidativo que ocorre nas mitocôndrias. Danos as estas organelas podem levar ao decréscimo da produção de energia, tendo um impacto direto sobre a performance cardíaca. Ainda, ao interagir com as células, a radiação ionizante pode gerar uma série de eventos bioquímicos que conduzem a uma resposta celular complexa, em que muitas proteínas parecem estar envolvidas. Tendo em vista tais conhecimentos, o objetivo do estudo foi avaliar o aspecto ultraestrutural do tecido cardíaco, a bioenergética mitocondrial e a expressão diferencial de proteínas após irradiação. Os ensaios foram realizados em amostras de tecido cardíaco de ratos Wistar irradiados com dose única de 20 Gy direcionada ao coração. As análise tiveram início 4 e 32 semanas após irradiação. A análise ultraestrutural foi realizada através de microscopia eletrônica de transmissão. A respiração mitocondrial foi mensurada em oxígrafo, a partir das taxas de consumo de oxigênio pelas fibras cardíacas. A identificação de proteínas diferencialmente expressas foi investigada através de duas técnicas proteômicas: 2D-DIGE (2-D Fluorescence Difference Gel Electrophoresis) e uma abordagem label-free seguida de espectrometria de massas. Os resultados mostraram que os efeitos tardios da radiação incluem a degeneração das mitocôndrias e das unidades contráteis do tecido cardíaco, disfunções na cadeia respiratória mitocondrial e expressão diferencial de proteínas envolvidas no metabolismo energético de carboidratos, lipídeos e da fosfocreatina. De forma geral, o estudo mostrou que a irradiação cardíaca prejudica o processo de síntese energética, conduzindo a um déficit da taxa respiratória mitocondrial como efeito tardio. Tal evento pode culminar em disfunções mecânicas no coração, caracterizando o desenvolvimento de doenças cardíacas radioinduzidas. / During radiotherapy for tumors located at toracic region, part of the heart is often included in the treatment field and may receive a significant ionizing radiation dose comparing to the therapeutics. Heart irradiation is able to cause substantial cardiac complications to patient, characterized by functional progressive changes from 10 to 20 years after the exposure of the organ. Because of its high level of contraction and large energetic consumption, cardiac tissue is highly depending on oxidative metabolism which happens at mitochondrias. Damage to these organelles can lead to decreased energy production, having a direct impact on cardiac performance. Even when interacting with cells, ionizing radiation can generate a series of biochemical events that lead to a complex cellular response, in many proteins seem to be involved. Given this knowledge, the aim of the study was to evaluate the ultrastructural appearance of cardiac tissue, mitochondrial bioenergetics and differential expression of proteins after irradiation. The tests were performed on samples of cardiac tissue of rats irradiated with single dose of 20 Gy directed to the heart. The analysis started 4 to 32 weeks after irradiation. The ultrastructural analysis was performed by transmission electron microscopy. Mitochondrial respiration was measured in oxigraph from rates of oxygen consumption by cardiac fibers. The identification of differentially expressed proteins was investigated using two proteomic techniques: 2D-DIGE (2-D Fluorescence Difference Gel Electrophoresis) and a label-free approach followed by mass spectrometry. The results showed that the late effects of radiation include degeneration of mitochondria and contractile units of cardiac tissue, dysfunction in the mitochondrial respiratory chain and differential expression of proteins involved in energy metabolism of carbohydrates, lipids and phosphocreatine. In general, the study showed that the cardiac irradiation damages the process of synthesis energy, leading to a deficit in mitochondrial respiratory rate as late effect. Such event may result in mechanical dysfunction in the heart, characterizing the development of radiation-induced heart disease.

Abstract Primary intracerebral hemorrhage (ICH) accounts for 10–15% of all strokes. ICH is the most devastating subtype of stroke with high mortality and morbidity; 35–52% of patients die during the first month after the bleeding. The most important risk factor for onset of ICH is hypertension, especially untreated hypertension, and the well-known predictors for early death after ICH are a low GCS (i.e low level of consciousness) score on admission, the size of the hematoma, and the precence of intraventricular blood. Preceeding use of anticoagulants and advanced age further impair the outcome. Thromboembolic complications after the bleed are common and difficult to prevent. The present cohort study included all patients (n = 453) with verified primary ICH admitted to the stroke unit of Oulu University Hospital within a period of 11 years (from January 1993 to January 2004). The impacts of previous diseases, including ischemic heart disease, atrial fibrillation on admission, hypertension, and diabetes as well as of high admission blood pressure and plasma glucose levels on outcome were evaluated. The safety and efficacy of prevention of venous thromboembolism with enoxaparin, a low molecular weight heparin (LMWH), was investigated. In a population-based study covering a 3-year period, the risk factors and seasonal distribution of ICH were investigated. Independent of the severity of bleeding and patients’ age, ischemic heart disease, diabetes, and atrial fibrillation were found to be significant predictors for early death after ICH. High blood pressure on admission predicted early death, whereas elevated admission plasma glucose level was associated with the severity of bleeding but was not an independent predictor for early death. Treatment with enoxaparin (20 mg per day subcutaneously) for prevention of venous thromboembolism was not associated with increased mortality but did not seem to prevent venous thromboembolic complications. The incidence of ICH was higher during the winter among patients with untreated hypertension but not in normotensive and treated hypertensive patients.

No description available.

Cardiac disease is the primary cause of death in the United States of America (CDC, 2017). Despite ongoing efforts and investments to improve cardiac health in the United States, most of the population will suffer from cardiovascular diseases. There is a multitude of research supporting that diet can contribute to cardiac disease, but it is less known that diet can greatly contribute to regulation and reversal of cardiovascular disease processes (Huang et al., 2012; Satija et al., 2017; Kim et al., 2019). Existing research supports the efficacy of plant-based diets to manage and reverse certain cardiac diseases (Tuso et al., 2015; Esselstyn, 1999; Ornish 1998; Campbell et al., 1998). Plant-based diets have the potential to save many lives and drastically reduce healthcare costs. The purpose of this literature review is to evaluate current research on plant-based diets as interventions for cardiac disease and to identify the reasoning for underutilization of plant-based diets as intervention with cardiac health within the United States population. A database search of CINAHL Plus, MEDLINE, BIOSIS, Cochrane, Google Scholar, and PubMED was conducted and university librarians were utilized. Inclusive criteria and keyword searches were comprised of coronary artery disease and plant-based diets, cardiac disease and diet interventions, intensive lifestyle changes for reversal of coronary heart disease, plant-based diets and cardiac disease and inflammation, and plant-based diets reducing cardiac inflammation.

Tumor necrosis factor (TNF) is upregulated in a number of cardiomyopathies. This thesis investigates TNF in triggering the expression and activation of matrix metalloproteinases (MMPs) in pressure overload cardiac disease, and explores the role of superoxide. Cardiac pressure overload was generated in adult wild-type and TNF-/- mice by transverse aortic constriction. Isolated cardiomyocytes and cardiofibroblasts from neonatal mice ventricles were treated with recombinant TNF (rTNF), and MMP induction and activation were assessed, with and without apocynin (a NADPH-oxidase inhibitor). TNF-/- mice showed less superoxide production and MMP activation, compared to wild-type mice, following pressure overload. rTNF upregulated the production of NADPH-dependent superoxide in cardiomyocytes as early as 1 hour (24 hours in cardiofibroblasts). rTNF also increased the expression of MMP-9 and MMP-12 in cardiomyocytes more than in cardiofibroblasts, and MMP-8 and MMP-13 more in cardiofibroblasts. This induction in both cardiac cell types was concomitant with superoxide production.

No description available.