The advent of hyperpolarized magnetic resonance (MR) has provided new potential for real-time visualization of in vivo metabolic processes. The aim of the work in this thesis was to use hyperpolarized substrates to study rapid metabolic processes occurring in the healthy and diseased rat heart. Initial work, described in Chapter 2, optimized the hyperpolarization process to reproducibly generate tracers. Chapter 3 describes use of hyperpolarized 1-13C-pyruvate to investigate in vivo flux through the regulatory enzyme pyruvate dehydrogenase (PDH). Cardiac PDH activity was altered in several physiological and pathological states, namely fasting, type 1 diabetes, and high-fat feeding, and in vivo flux through PDH was measured using hyperpolarized MR. These measurements correlated with measurements of in vitro PDH activity obtained using a validated biochemical assay. The work in Chapter 4 investigated the physiological interaction between hyperpolarized tracer and cardiac tissue. The effect of hyperpolarized 1-13C-pyruvate concentration on its in vivo metabolism was analyzed using modified Michaelis-Menten kinetics. It was found that hyperpolarized MR could non-invasively follow mechanisms of metabolic regulation, in addition to reporting enzyme activity. In Chapter 5, hyperpolarized MR was incorporated into the isolated perfused rat heart. 1-13C-pyruvate in normal and ischaemic hearts revealed significant differences in lactate metabolism, and provided the foundation for a novel intracellular pH probe. Infusion of 2-13C-pyruvate in the isolated rat heart enabled the first real-time visualization of Krebs cycle intermediates. In summary, the work in this thesis has highlighted the potential of hyperpolarized MR to reveal novel information on heart disease.

Hospital readmissions are a source of reduced payment as mandated by the Centers for Medicare and Medicaid Services as part of the Affordable Care Act (ACA). The number of dollars used for hospital readmissions has sky rocketed above $17 million for heart failure alone. The changes in the ACA reimbursement guidelines has put stress on many hospitals as they are facing reduced income, increased use of resources, and increased length of stay. This project evaluated the implementation of Project BOOST, its components, and their predictability for hospital readmission. Sample groups were evaluated both pre- and post-implementation of Project BOOST, which included individuals aged 18 and older, who were of Anglo, Hispanic or Native American descent, and living in Northern Arizona. A retrospective chart review was performed and descriptive and predictive statistics were used to analyze obtained data. Patients with cardiovascular disease admitted to the study hospital have high risks for readmission, such as problem medications, polypharmacy, psychological Issues, and principal diagnoses. Integrating elements from Project BOOST significantly decreased 30-day hospital readmissions. Data from this study revealed a statistically significant reduction in 30-day hospital readmission rates from 22% in the pre-intervention period to just 4% in the post-intervention period. Patients who did not receive the risk assessment tool were 14 times more likely to be readmitted to the hospital within 30 days of the index hospitalization.

Background: There is mounting evidence to indicate that periodontitis may be a risk factor for cardiovascular disease (CVD). Periodontitis may be linked to CVD as either an etiologic mechanism or a predisposing factor that can hasten disease progression. Proinflammatory cytokines, elevated fibrinogen, and platelet aggregation are all potential mechanisms. The purpose of this study is to compare and review the serological differences in subjects with severe periodontitis, some of which involve established risk factors for atherosclerosis, particularly heightened C-reactive protein levels. Methods: A total of 184 subjects, comprising of two periodontal subgroups, non-periodontal (NP = 91) and generalized aggressive periodontitis (SP = 93), had serum evaluated for C-reactive protein (CRP) levels using a high sensitive ELISA test. The CRP levels were compared against clinical and demographical data to include race, age, gender, number of teeth, probing depth, attachment level, bleeding index, plaque index, and gingival index. Results: After adjusting for potential confounding variables, probing depth (p Conclusion: Pocket depth is significantly related to elevated levels of CRP, which is why it is imperative to treat periodontal pockets. This study may provide a possible link between CRP and periodontal disease, but a causal relationship cannot be inferred.

Background: Hypertension is a major public health concern for African American women. Many studies have shown a greater prevalence of hypertension, as well as physical inactivity, excess weight, and diabetes, in African Americans. Objective: To determine if differences in eating patterns, as measured by Healthy Eating Index (HEI) scores, between African American women and other women in the United States are associated with hypertension. Methods: Data were extracted from the Third National Health and Nutrition Examination Survey (NHANESIII). The sample included 31,189,534 women aged 45 years or greater after survey weights were applied. The majority was White (86.1 %); minority groups included African Americans (10.5%) and Mexican Americans (3.4%). Women were considered to have hypertension if they reported that a doctor diagnosed them. Other predictor variables included age, body mass index, income, education, marital status, residence, health insurance coverage, regu1a.r source of care, smoking history, hypercholesterolemia, history of myocardial infarction, attempted weight loss, and physical activity level. The Cochran Mantel Haenszel (CMH) statistic and logistic regression were used to determine the magnitude of the association of study variables with the outcome. Results: African American women were more likely to have hypertension than White and Mexican American women. Diet, based on the HE1 score, was significantly related to the development of hypertension (CMH chi-square = 428.39, p-value = Conclusions: These findings provide further support the need to established interventions that target this population. The key to prevention is education and promotion of healthier eating habits.

Sudden cardiac death represents one of the leading causes of death worldwide, with the majority of these deaths caused by arrhythmias derived from ischæmic events. However, the mechanisms leading from ischæmia to re-entry, arrhythmia and eventual death are poorly understood. Furthermore, variability in the action potential of cardiac tissue, while important in determining arrhythmic risk, is only recently being addressed in computational modelling, with little known about the causes and mechanisms underlying it, nor regarding its evolution in response to pathological conditions such as ischæmia. This dissertation investigates the causes of variability in the repolarisation of the action potential of the rabbit ventricular myocyte, and the response of this variability to ischæmia. The effect of variability in ion channel conductances is investigated by means of a complete search of the parameter space revealed by simultaneous variation in multiple parameters describing ion channel conductances in computational models of the rabbit ventricular action potential. Rabbit data and models are used in this thesis due to the similarities to human data, both in terms of electrophysiology generally, and the response to ischæmia specifically. The response of two different model frameworks is assessed to determine similarities and differences between model frameworks that are designed to reproduce the same system. Those models producing action potential durations that fall within an experimentally derived range at multiple pacing rates are used to define model populations that thus reproduce experimental variability in repolarisation. These model populations are used to investigate the effects of ischæmic conditions on population variability. Variability is measured not only for action potential duration, but also for other biomarkers commonly implicated in the development of re-entry. The work presented in this dissertation is significant for: (1) presenting a comprehensive study of the effect of simultaneous variation in ion channel conductances, with details regarding the interactions between conductances and how these interactions change depending on the pacing rate; (2) detailed examination of the differences between two models of the same system; (3) production of the largest extant populations reproducing experimentally observed variability in action potential duration; (4) the first time model populations have been used to investigate the effects of ischæmia on variability.

Hypoxia inducible factor-1α (HIF-1α) plays a critical role in the oxygen homeostasis of all metazoans. HIF-1α is a master transcriptional regulator which coordinates the adaptive response to low oxygen tension. Through activation of a plethora of downstream target genes, HIF-1α facilitates oxygenation by promoting angiogenesis and blood vessel dilation, in addition to modulating metabolic pathways to inhibit oxidative phosphorylation and promote glycolytic energy production. Given the critical roles of hypoxia, insufficient blood supply and perturbed energetics in the pathogenesis of cardiovascular disorders, notably ischaemic heart disease, therapeutic modulation of HIF-1α is of significant clinical interest. Previous studies have demonstrated an acute cardioprotective role for both endogenous and supraphysiological HIF-1α signalling in the context of myocardial ischaemia. In contrast, chronic supraphysiological HIF-1α activation in the unstressed heart has been shown to induce cardiac dysfunction. To address the effect of chronic endogenous HIF-1α activation post-myocardial infarction (MI), the present work employed a murine coronary artery ligation (CAL) model in conjunction with temporally-inducible, cardiac-specific deletion of Hif-1α. While CAL surgery successfully modelled myocardial infarction – eliciting substantial adverse cardiac remodelling and contractile dysfunction – there was no evidence of chronic HIF-1α activation by CAL in HIF knockout or control left ventricular samples. In keeping with this, chronic ablation of Hif-1α (from 2 weeks post-CAL) had no discernible additional effect upon cardiac function. Overall, these findings do not support a potential therapeutic role for inhibition of HIF-1α signalling in the chronic phase post-MI. The fundamental tricarboxylic acid (TCA) cycle enzyme fumarate hydratase (FH) converts fumarate to malate. FH deficiency is associated with smooth muscle and kidney tumours which exhibit normoxic HIF signalling due to fumarate accumulation. To investigate the potential for fumarate accumulation to elicit protective HIF signalling, a cardiac-specific Fh1 null mouse was developed through Cre-loxP recombination. Strikingly, despite interruption of the TCA cycle in a highly metabolically demanding organ, cardiac Fh1 null mice were viable, fertile and survived into adulthood, demonstrating the remarkable metabolic plasticity of the heart. However, by 3-4 months Fh1 null mice develop a lethal cardiomyopathy characterised by cardiac hypertrophy, ventricular dilatation and contractile dysfunction. Despite lack of a pseudohypoxic response, Fh1 null hearts did exhibit another phenomenon observed in FH-deficient cancers and also attributed to fumarate accumulation – activation of the nuclear factor (erythroid-derived 2)-like 2 (NRF2) antioxidant pathway. Heterozygous, but not homozygous, somatic deletion of Nrf2 extended the life expectancy of cardiac Fh1 null mice. Exploration of redox status revealed a more reductive environment in Fh1 null hearts than controls. As a corollary, inhibition of the rate limiting enzyme of the pentose phosphate pathway – a major source of cellular reducing equivalents – with dehydroepiandrosterone conferred striking amelioration of the Fh1 null cardiomyopathy, suggesting a possible pathogenic role for reductive stress. While loss of mitochondrial Fh1 activity and subsequent TCA cycle dysfunction likely contribute to the Fh1 null phenotype, the importance of cytosolic FH was unclear. To clarify this, FH was expressed specifically in the cytosol in vivo. This was sufficient to substantially rescue the Fh1 null cardiomyopathy, supporting a role for cytosolic FH disruption in its pathogenesis. Taken together, these findings highlight the potential for reductive stress to contribute to cardiac dysfunction and suggest a function for cytosolic FH in cardiac metabolic homeostasis.

1 Abstract: Title: The importance of primary and secondary prevention of cardiovascular disease Goals: Develop a theoretical basis for the selected topic. Describe the basic principles of primary and secondary prevention, and thus prepare the groundwork for creating questionnaires. Questionnaire compiled to complement the information obtained from the literature on insight into the practice. Confirm or refute the hypotheses chosen on the basis of a questionnaire. Discuss the most frequently occurring phenomena and compare them with the latest reported information. Draw conclusions and recommendations. Method: For the theoretical treatment of the retrieval method was used. I compared the information and inclined to the best proven. The theoretical part resulted in the goals and tasks of work. For the practical part was conducted by questionnaire survey, which has additional information on the issue of primary and secondary prevention. In the end I obtained data compared with information obtained from studying literature. Results: Lack of information on primary and secondary prevention is mainly for young people aged 10-15 years. This trend is accompanied by the deteriorating health situation and the occasional occurrence of the "diseases of civilization", which can produce complications in adulthood....

Background: This study explored the differences between the seasonal mortality rates (by age and gender) between the two jurisdictions (the Republic of Ireland (RoI) and Northern Ireland (NI)). The study assessed the relationship between cold temperatures and daily mortality, and assessed for effect modification of the cold weather-mortality relationship by age and gender. Methods: Mortality rates were calculated for each cause-specific mortality group during various seasons in both jurisdictions. A time-stratified case-crossover approach was applied to examine the cold weather-mortality relationship, 1984-2007. The daily mortality risk was explored in association with exposure to daily maximum temperatures on the same day and up to 6 weeks preceding death, during the winter months and extended cold period (October-March), using distributed lag models. Model stratification by age and gender assessed for modification of the cold weather-mortality relationship. Results: The winter mortality rates were significantly greater than the summer rates. NI experienced higher mortality from cardiovascular disease, respiratory disease and stroke. The impact of cold weather in the winter months persisted up to 35 days in the RoI, with a cumulative mortality increase for all-cause of 6.4% (95%CI: 4.8%-7.9%) with regards to every 1oC drop in the daily maximum temperature with similar associations for cardiovascular disease and stroke with twice as much for respiratory diseases. The associations were less pronounced and less persistent in NI. Conclusions: The study observed excess winter mortality. The cold weather-mortality associations increased with age with some suggestion of gender differences. There were strong cold weather-mortality associations in both jurisdictions, with suggestive differences in associations by age and gender. The findings suggest the potential contribution of societal differences, and require further exploration. These findings will hopefully contribute to the current efforts to modify fuel policy and reduce winter mortality in both jurisdictions.

I detta arbete bearbetas forskning om eHälsa, dess användande inom vården och motivationsteorierna Transteoretiska modellen, Maslows behovshierarki och självbestämmandeteorin. Vidare presenteras egna observationer på hur vården i dagsläget kan stötta patienter med hjärtkärlsjukdom till bättre levnadsvanor, samt intervju med uppföljning på hur en PCI-patient upplever att ta emot kost- och träningsrekommendationer via ett digitalt hälsoverktyg.   Syftet är att med en fallstudiedesign undersöka hur vården stöttar hjärtpatienter till bättre levnadsvanor och om digitala hälsoverktyg kan öka den upplevda motivationen hos PCI-patienter till att äta bättre och aktivera sig mer.   Metoderna som använts är kvalitativa, där resultaten bygger på en halvdags observationer på en fysioterapeutmottagnings arbete med hjärtkärlpatienter och en intervju samt uppföljning med en PCI-patient som använt ett digitalt hälsoverktyg under tio dagars tid.   Huvudresultatet från denna studie tyder på att någon form av stöd är viktigt för att uppleva sig kunna börja och klara en förändringsprocess. Motivationen tycks öka av socialt stöd eller stöd som bidrar till ökad kompetens och självbestämmande, varav det första exemplifieras vid observationerna av vården, och de andra två gick att se blev positivt påverkade hos PCI-patienten efter sin användning av det digitala hälsoverktyget. Patienten upplevde sig mer motiverad av att alltid ha informationen lättillgänglig, att det gick att individanpassa efter sig själv och gav inspiration, samt ett mervärde av kunskap.   Patienten började äta bättre och ta dagliga promenader på egen hand, från att tidigare upplevt sig ”glömma” och föredragit en bilresa till att få promenera med andra än att promenera själv. Patienten beskriver även ett förbättrat självförtroende och mer positiv framtidssyn.   Dock behöver detta testas i större skala för att kunna uttala sig om det skulle kunna ge effekter på en majoritet och om dessa effekter skulle vara bestående. Men en öppenhet för framtiden bör finnas för att eHälsoverktyg kan fungera som ett stöd, vara informerande och kanske till och med motiverande när det behövs. / In this study research about eHealth, its usage in health care and the motivation theories Transtheoretical model, Maslow’s hierarchy of needs and the self-determinant theory is processed. The study is also presenting results from personal observations on how the health care supports patients with cardiovascular disease to better habits and an interview with a follow-up on how a PCI-patient is experiencing receiving eating and exercising recommendations through a digital health tool.   The purpose of the case study is to find out how the health care supports patients with cardiovascular disease to better eating and exercising habits, and if digital health tools can increase the experienced motivation to eat better and exercise more.   The methods that have been used are qualitative, and the results are based on observations of the work with patients who have cardiovascular disease, conducted at a physiotherapist’s office and an interview with a follow-up with a PCI-patient who used a digital health tool for ten days.   The main result of this study indicates that some kind of support is essential to feeling able to start and make a process of change. The motivation seems to increase through social support or other support which contributes to higher competence and self-determination. The patient felt more motivated by always having the information easily accessible, the fact that the tool was customizable to his own needs and that it gave him inspiration and knowledge.   The patient began to eat better and take daily walks on his own. Previously he had ”forgotten” and preferred to drive to town just to walk together with other people rather than just walking by himself. The patient also describes an improved self-confidence and has a more positive vision of the future.   However, this needs testing in a larger scale to be able to express whether it could effect a majority, and if these effects would be permanent. Nevertheless, an openness for the future should exist regarding eHealth tools to work as a support, to be informative and perhaps even motivating when needed.

This research of teleconsultation services aims to improve the quality of diagnosis and treatment for rural cardiovascular patients through utilizing distant medical expertise. Equitable access to expert healthcare as well as improved medical management for these patients can assist in modifying cardiovascular disease (CVD) risk and reduce morbidity and mortality in Saudi Arabia. The objectives were to design and develop a new care pathway for cardiovascular disease patients by utilizing teleconsultation technology, investigate factors and issues that might act as barriers to its adoption, and then evaluate the impact of this model on the stakeholders. A small scale pilot project was used to determine the issues of technology, processes and human resources required to deliver an effective service with the context of the research setting. Four primary healthcare centres, two regional hospitals, fifteen patients and sixty other participant stakeholders were included in this study. An approach using (PCP) patient care pathways was used to introduce the teleconsultation technology and integrate it within the healthcare delivery system. Compared to the traditional PCP, the modified PCP utilising teleconsultation technology improved the quality of healthcare through:  Improved access to medical care and quality of diagnosis by obtaining the expertise of a distant specialist.  More efficient medical evaluation and management.  Enhanced role of primary healthcare centres and participating hospitals by providing all levels of health services for patients.  Evidence-based referral (reduced waiting time, reduced burden on outpatient clinics). The telconsultation adoption barriers included:  Inadequacy of finance  Limited infrastructure  Legal and regularity difficulties.  Organization issues.  Literacy on technology. This study recommends the following for telemedicine implementation in the country:  Promote perception and readiness for ICT services with the healthcare community.  Enhance structural readiness including appropriate infrastructure and adequate funding, human resources and equipment.  Proactive policies to encourage growth of the telecommunication sector and to address concerns regarding privacy and security.