Implantation of a left ventricular assist device (LVAD) is a potential treatment in terminal heart failure. Right ventricular (RV) failure is a severe complication in these patients and sometimes requires additional placement of a right ventricular assist device (RVAD). RVAD implantation, however, is an invasive treatment associated with both increased mortality and morbidity. The aim of this thesis was to study whether partial volume exclusion of the RV through a modified Glenn shunt or cavoaortic shunt could treat severe RV failure. The ultimate goal would be to use it as an alternative to a RVAD in RV failure during LVAD therapy. Swine were used as the model animal in all studies. In Study I, experimental RV failure was induced by ischemia, and verified by hemodynamic measurements and genetic expression. Treatment with a modified Glenn shunt reduced venous stasis and improved hemodynamics in general. In Study II, experimental RV failure was induced by the same method as in Study I. Treatment with a cavoaortic shunt in addition to LVAD therapy proved to reduce venous stasis and improved hemodynamics in general, which was feasible with preserved oxygen delivery despite cyanotic shunting. In Study III, experimental RV failure was induced by pulmonary banding, and verified by hemodynamic measurements and genetic expression. Treatment with a modified Glenn shunt reduced venous stasis but did not improve hemodynamics in general compared with a control group. In Study IV, the effects of LVAD therapy and subsequent treatment with a modified Glenn shunt on the normal RV function were studied. It demonstrated that LVAD therapy can put strain on the RV by increasing stroke work and end-diastolic volume, and that these effects can be reversed by treatment with a modified Glenn shunt during LVAD therapy. In conclusion, partial volume exclusion through a modified Glenn shunt or cavoaortic shunt is a feasible treatment of experimental RV failure. Thus, it could potentially be used as an alternative treatment to a RVAD in severe RV failure during LVAD therapy.

Effective treatment of heart disease and an aging population have led to increases in the incidence of heart failure. Treatment requires complex medication regimes and recognition of symptoms. Best practice guidelines published by the American, European and Canadian cardiac societies promote self-care behaviours and skill building. No concrete examples of education programmes for clients were found in the literature. The purpose of the study was to develop, pilot and evaluate an education series for clients with heart failure within a primary care setting. “LEARN twice”, a three part education series with related resource material, was developed in the context of inter-professional collaboration and drew upon theories of health education, and literacy. The concept of co-management was incorporated as the philosophical basis in the design. The pilot-test used an experimental design, and incorporated pre and post-testing with standardized instrumentation including the Dutch Heart Failure Knowledge Scale and the Minnesota Living with Heart Failure Questionnaire. To pilot the education series, participants attended three education classes highlighting the essential skills for self management of heart failure. A qualitative descriptive component included brief semi-structured interviews with participants and educators to provide feedback about both the process and content of the educational series. Limited participant numbers did not permit statistical testing, however potentially promising results were found in the quantitative data collected. Descriptive participant data indicated that the education series was meaningful, and helped iii understanding of symptoms. Instructors rated the content as good to excellent and anticipate the adoption of the education series as standard practice in the clinic. The pilot test of the education series has provided a foundation for future research endeavours, in particular the replication and completion of this study protocol. As clients with heart failure have the potential to be in regular contact with a primary care provider, subsequent studies could include a longitudinal component to examine whether rates of re-hospitalization are reduced for clients who attend an education series.

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.