Prolonged prenatal hypoxia has shown to cause fetal growth restriction inchickens due to restricted oxygen to the somatic tissue. The body goes through a critical periodof development. Insults during this critical period may have lifelong effects on the individual.Currently heart failure is treated either with symptomatic therapy using diuretics or by targetingthe renin-angiotensin-aldosterone system. Developing new successful treatments is importantwith the aging population and the increased rate of heart failure. Previous studies have shownsystolic contractile dysfunction in 5 week old broiler chicken hearts when the eggs have beenincubated in hypoxia until hatching. S100A1 in cardiomyocytes regulates the calcium-controllednetwork which plays a big role in cardiac contractility and in this study, using qPCR on S100A1(GOI), GADPH and β-actin to try and determine if the changes made to the heart while the fetusis developing is due to a lack of S100A1 expression resulting in a decreased handling of Ca2+uptake which causes contractile dysfunction A Roche Lightcycler 480 was used together with theRoche template running triplets of each sample at 15-15-15 seconds for 45 cycles No statisticalsignificance was observed between the control group and the experimental group. However inthis study only S100A1 gene is being considered but a better understanding of the whole S100family might give a better understanding of mechanisms causing the progressive deterioration ofcardiac function

No description available.

Blood-derived circulatory angiogenic cells (CACs) and resident cardiac stem cells (CSCs) have both been shown to improve cardiac function after myocardial infarction (MI) but the superiority of either cell type has long been an area of speculation with no definitive head-to-head trial. In this study, we compared the paracrine profile of human CACs and CSCs, alone or in combination. We characterized the therapeutic ability of these cells to salvage myocardial function in an immunodeficient mouse model of MI by transplanting these cells as both single and dual cell therapies seven days after experimental anterior wall MI. CACs and CSCs demonstrated unique paracrine repertoires with equivalent effects on angiogenesis, stem cell migration and myocardial repair. Combination therapy with both cell types synergistically improves post infarct myocardial function greater than either therapy alone. This synergy is likely mediated by the complementary paracrine signatures that promote revascularization and the growth of new myocardium.

A qualitative phenomenological study incorporating Photovoice was conducted to gain insight into the lived experience of patients with end-stage heart failure (ESHF). Seven participants were recruited and in-depth open-ended interviews were conducted with all participants. Three of the seven informants also opted to take part in the Photovoice portion of the project. “Working to preserve a sense of self” emerged as the essence of living with ESHF and was supported by three themes: i) the work of managing a failing and unreliable body, ii) the work of choreographing daily living; and iii) the work of charting the final chapter of one’s life. The findings from this study provide healthcare professionals with empirically grounded information and insights about the needs and everyday challenges individuals living with ESHF experience, and how clinicians can best support them. Such information is essential in order to plan meaningful, holistic, evidence-based care for ESHF patients.

Understanding the molecular basis of doxorubicin (Dox)-induced oxidative stress leading to cardiomyopathy is crucial to finding cardioprotective strategies to manage this important clinical problem. Improving the antioxidant defenses of cardiac cells could be one strategy for cardioprotection. The role of oxidative stress in Dox-induced cardiotoxicity as well as testing the efficacy of antioxidant Vitamin C (Vit C) in offering protection to cardiomyocytes was investigated. As stem cells have been suggested to play a role in this cardiotoxicity, Dox-mediated oxidative stress effects, with and without Vit C, on the stem cell antigen-1 (Sca) positive cells from heart as well as bone marrow were also examined. Our time-course studies of the effects of Dox on the isolated cardiomyocytes showed that the phosphorylation of mitogen-activated protein kinases and p53 followed the rise in reactive oxygen species (ROS) production. Dox also downregulated the Sodium-dependent Vit C Transporter-2 (SVCT-2) and this may have enhanced Dox-induced increase in oxidative stress. Pro-apoptotic markers Bax/Bcl-xL ratio and caspase 3 cleavage were higher after the activation of stress-induced pathways and viability of cells was decreased. Dox-induced increase in apoptosis and decrease in cell viability depended in part on the activation of p38/JNK and p53 proteins, but not on the ERK protein. Exposure to Dox, increased membrane leakage, autophagy and lipid peroxidation. On the other hand, Dox decreased overall antioxidant capacity as well as expression of the endogenous antioxidant enzymes glutathione peroxidase, Cu/Zn superoxide dismutase and catalase. Dox affected Sca-1 positive cells in a prominent manner which was marked by a dose-dependent increase in cell loss, cell leakage and ROS levels as well as decrease in cellular ATP levels. Vit C pre-treatment prior to the addition of Dox delayed and reduced Dox-induced injury to cardiomyocytes, preserving viability. Vit C was able to blunt the decrease in SVCT-2 as well as Dox-induced oxidative stress. Vit C also offered protection to Sca-1 positive cells by partially preventing Dox-induced changes to these cells. The data presented in this thesis improves our knowledge of the molecular mechanisms leading to Dox-induced cardiotoxicity as well as suggest cardioprotection by Vit C.

No description available.

Background: Symptomatic heart failure is a chronic and disabling condition that affects over 350 000 Canadians and is characterized by inevitable progression. Historically, research on the ways to increase survival has focused on biomedical factors. However, the continued poor prognosis of heart failure has prompted the search for other ways to improve the lives of these patients. Research in other chronic conditions demonstrates that social circumstances, described collectively as individual social interactions (e.g. social support, social participation) and community social factors (e.g. social capital, social norms), can influence health outcomes. Purpose: The purpose of this research was to describe and assess the impact of selected social circumstances potentially related to heart failure outcomes. Methods: Two literature reviews and one empirical study were performed. Conceptual models were proposed to describe the hypothesized pathways between selected social circumstances and heart failure outcomes. The first review was a systematic review of quantitative studies evaluating the relationship between social support and both rehospitalization and death. The review included a critical analysis of the methods employed by previous studies. The second review integrated the qualitative and quantitative literature describing the relationship between individual social interactions (including support, roles and participation) and the quality of life of patients or experience of living with heart failure. A narrative summary was provided and an integration of findings from both qualitative and quantitative study designs was performed. In the empirical study, patients‘ demographic and clinical information was examined simultaneously with selected community factors in a multilevel analysis. Outcomes of interest included rehospitalization or death of heart failure patients. Results: The systematic review shows that previous quantitative research has linked social support to reduced rehospitalization, but there is little evidence to link it with prolonged survival. The critique of the methods describes an inadequate conceptualization and inconsistent measurement of social support. A conceptual model showing how social support can influence rehospitalization is proposed. The integrative review presents qualitative research that identified the following social interactions as important components of the heart failure experience: social support, social participation and role fulfillment. However, no quantitative relationship between social support and quality of life was found. The potential reasons for the discrepant findings between the qualitative and quantitative studies include: the focus on social support as the only component of social interactions assessed in the quantitative literature; and the inconsistent measurement of social support. A conceptual model is presented to describe the multiple components of social interactions and the theoretical basis for their effects. The multilevel analysis demonstrates that individual factors exerted the strongest effect on heart failure outcomes in most models. Community characteristics had little influence on rehospitalization or death. Study design and analysis issues are proposed to explain these findings. Conclusion: The literature reviews and the empirical study provide a contribution to the population health literature, offering a broad approach to assessing the determinants of disease progression in heart failure patients. This thesis research advances the discussion about which social circumstances may influence heart failure outcomes and their pathways. The use of the proposed conceptual models in future research will help clarify the role of social circumstances in the prognosis of heart failure.

Background: Patients with heart failure (HF) are characterized by exercise intolerance, breathlessness, fatigue and excessive neurohormonal activation associated with premature mortality. Recently, inflammatory activation has been described as an important factor in the progression of HF. Increased levels of certain pro-inflammatory cytokines (e.g., TNF-ɑ, IL-6) have been related to increased severity of left ventricular dysfunction, the activation of the sympathetic and renin-angiotensin systems and the catabolism of skeletal muscle. Although exercise training is important in the management of HF, acute bouts of exercise may lead to increases in proinflammatory cytokines. It is believed that the skeletal muscle abnormalities associated with HF may increase the risk of damage to skeletal muscle, (i.e., exercise-induced muscle injury (EIMI) with associated inflammatory activation) especially following unaccustomed exercise training. Recently, several training methods have been proposed for patients with HF that challenge the traditional “steady-state” (SS) training model, including interval training (IT). Interval training methods employ greater muscular loading than SS and therefore may increase the risk of inflammatory system activation EIMI, and/or reduced muscle function. There is no study that has examined the effects of IT on EIMI, muscle function and/or inflammatory markers. Material and Methods: Fourteen male participants with HF (mean age: 59 +/- 7.8 yrs; mean VO2 peak: 13.64 +/- 4.5 ml/kg/m-1; EF < 45%) were matched (for body mass and aerobic fitness) and randomized into SS or IT for 20 minutes. The IT involved 2 minute work:recovery phases of 90% and 40% of heart rate reserve, respectively. The SS involved continuous exercise at 65% of heart rate reserve. Biochemical markers of muscle damage and acute inflammation, concentric and eccentric isokinetic muscle torque, and subjective indicators of delayed onset muscle soreness (DOMS) and lower extremity function were evaluated at baseline, and then immediately following the training bout, and at 6, 24, and 48 hours post. Results: There were no significant differences between the IT and the SS training group for markers of skeletal muscle injury or inflammatory activation. Conclusions: The findings from the present study suggest that IT or SS do not result in excessive inflammatory system activation or skeletal muscle injury. These results have important implications for clinicians prescribing exercise regimes for HF patients who may be starting back into activity after a prolonged sedentary period. Additionally, results from this study indicate that there is a need for future research looking at the actual and perceived effect of even a single about of exercise on lower extremity function.

Background and aims: Heart failure (HF) is a common health problem worldwide. Despite its importance, the epidemiology of HF is incompletely understood. Frequent references to an ‘epidemic of HF’ are at odds with recent reports of a decline in mortality from heart failure. In addition, reports based on admissions to hospital with a diagnosis of HF show that an earlier upward trend levelled off in the late 1990s in most developed countries. However, HF is a heterogeneous condition with multiple underlying causes. A decline in the severity of acute myocardial infarction (AMI), one of the major underlying causes of HF, and improvement in the treatment of patients with AMI as well as of hypertension are factors that might produce contradictory effects on the epidemiology of HF. Recent claims of a major contribution of improved survival after AMI to the reported epidemic of HF in the United States of America need to be examined in other populations. This thesis aims to define more precisely the epidemiological features of heart failure in Australia, and how these have evolved over the last decade. It examines secular trends in mortality, hospital admissions, incidence and survival related to HF. Methods: Trends in mortality from HF and admission to hospital with a diagnosis of HF are examined using computerized records of all deaths occurring in Australia for calendar years 1997-2003 and National Hospital Morbidity Data for financial years 1996-1997 to 2003-2004, obtained from the Australian Institute of Health and Welfare. A death or admission to hospital was defined as involving HF if at least one of the causes of death or one of the diagnoses of each separation was coded to any of the relevant rubrics within the International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) or 10th Revision, Australian Modification (ICD-10-AM). The analyses are based on age- and sex-specific death and hospital separation rates for HF either as underlying cause (or principal diagnosis) or mentioned anywhere on the death certificate (or recorded in any diagnostic position in the hospital electronic file) for each calendar or financial year. The investigation of trends in incidence and outcome of early-onset HF (HF complicating an index AMI within 28 days) and late-onset HF after AMI (HF developing 28 days after an index AMI) was based on the World Health Organization MONItoring trends and determinants of CArdiovascular disease (MONICA) register in Western Australia. The study included all residents aged 25-64 years of Perth, the capital city of Western Australia, who were admitted to hospital between 1988 and 1993 with non-fatal definite AMI and who had no history of AMI or HF in the hospital record. Trends in incidence and outcome of early- and late-onset HF were investigated using appropriate statistical methods. Results: From a total of 907,242 deaths occurring in Australia between 1997 and 2003, heart failure was coded as the underlying cause of death (UCD) for 29,341 (3.2%) and was mentioned anywhere on the death certificate in 135,268 (14.9%). Over this period, in both sexes, there were decreases in the absolute numbers of deaths and in the age-specific and age-standardized mortality rates for HF either as UCD or mentioned anywhere on the death certificate. HF was mentioned in 24.6% and 17.8% of deaths attributed to ischaemic heart disease and circulatory disease respectively, and these proportions remained unchanged over the period of study. In addition, HF as UCD accounted for 8.3% of deaths due to circulatory disease and this did not change from 1997 to 2003. From a total of 48,562,285 separations from hospital between 1996-7 and 2003-4, HF was coded as the principal diagnosis for 344,081 (0.8%) and was mentioned anywhere on the hospital record in 1,212,109 (2.5%). While the number of separations with HF remained stable, the age- and sex-standardized separation rate for HF recorded as principal diagnosis decreased from 2.0 per 1000 population in 1996-1997 to 1.7 per 1000 population in 2003- 2004. The corresponding values for HF recorded in any diagnostic position were 7.8 and 5.0 per 1000 population. From all patients (N = 4006) who met the criteria for first-ever, non fatal ‘definite’ AMI in the Perth MONICA Register, 897 (22.4%) had early-onset HF complicating the index event. After adjustment for age and sex, the odds of developing HF declined by 13% (odds ratio for the period 1989-1993 relative to 1984-1988 = 0.87, 95% confidence interval (95%CI): 0.75 to 1.01). After adjustment for age and history of diabetes and hypertension, the hazard of death in patients with early-onset HF (i.e. case fatality) declined by 26% (HR for the period 1989-1993 relative to 1984-1988 = 0.74, 95%CI: 0.57 to 0.96). Of 3109 patients who did not develop early-onset HF, 406 (13.1%) had at least one subsequent hospital admission with a diagnosis of HF (defined as late-onset HF). Following adjustment for age and sex, the hazard ratio for late-onset HF for the period 1989-1993 relative to 1984-1988 was 0.85 (95% confidence interval (95%CI): 0.69-1.04). History of diabetes and hypertension, current smoking, length of initial admission for AMI, recurrent acute coronary syndrome and coronary artery revascularization procedures were predictors of late-onset HF. After a median follow-up of 3.2 years and adjustment for age (≥70 years) and history of diabetes, the hazard of death in patients with late-onset HF did not change over the period of study (HR for year = 1.02, 95%CI: 0.98 to 1.06). Conclusion: For reasons discussed in the body of the thesis, the observed decline in mortality from HF measured as either number of deaths or rate probably reflects a real change in the epidemiology of HF. In addition, there was no increase in the number of hospital admissions involving HF and standardized rates of hospital separations fell in Australia between 1996 and 2004. These results do not support a major increase in the caseload of HF over recent years. In addition, a decline in the risk of early- and late-onset HF after AMI as well as all the evidence on decline in incidence and severity of coronary artery disease and hypertension argue against an increase in inflow from these two important risk factors of HF. However, taking all of the influences on the epidemiology of HF together, it is likely that because of the increasing number of older people, the number of new cases of HF will rise over the next few years, even if the incidence rate falls.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2007. / Härtill 4 uppsatser.