Cardiac crises (e.g. heart attack or bypass surgery) have been shown to be related to poorer patient psychological and relational functioning. While these studies assume that the event significantly impacts patients, they do not measure the specific ways by which the cardiac event impacts their lives. In the current study, new measures were developed and validated to assess specifically how the event emotionally impacts the patient’s life. I proposed that how these emotions are engaged in part accounts for the impact of the event on negative outcomes. Results showed that the greater the current impact of the cardiac event on patients, the greater their current levels of depression, anxiety and trauma. Further, greater emotional blocking (failure to willingly process emotions internally) was associated with less optimal psychological and relational functioning. Unexpectedly, greater disclosure of emotions to one’s partner was also related to diminished psychological health, but unrelated to relationship functioning. Thus, it appears disclosure in the current study reflects distressed “venting”, and blocking represents an unhealthy form of engaging negative emotions from the cardiac event. Implications for further research using the scales assessing the distinct components of the emotional impact of the event and the engagement of these emotions are discussed.

Cardiac crises (e.g. heart attack or bypass surgery) have been shown to be related to poorer patient psychological and relational functioning. While these studies assume that the event significantly impacts patients, they do not measure the specific ways by which the cardiac event impacts their lives. In the current study, new measures were developed and validated to assess specifically how the event emotionally impacts the patient’s life. I proposed that how these emotions are engaged in part accounts for the impact of the event on negative outcomes. Results showed that the greater the current impact of the cardiac event on patients, the greater their current levels of depression, anxiety and trauma. Further, greater emotional blocking (failure to willingly process emotions internally) was associated with less optimal psychological and relational functioning. Unexpectedly, greater disclosure of emotions to one’s partner was also related to diminished psychological health, but unrelated to relationship functioning. Thus, it appears disclosure in the current study reflects distressed “venting”, and blocking represents an unhealthy form of engaging negative emotions from the cardiac event. Implications for further research using the scales assessing the distinct components of the emotional impact of the event and the engagement of these emotions are discussed.

Dietary docosahexaenoic acid (22:6n-3, DHA) has been shown to exert beneficial effects on coronary heart disease including the prevention of ischemia reperfusion injury. The ability to acutely infuse DHA to the heart to prevent ischemia reperfusion injury is a potentialy valuable tool in planned surgery where reperfusion and/or ischemia will take place including coronary artery bypass surgery and angioplasty. In the present study, hearts from chow-fed (AIN-93M) Sprague Dawley rats (male) 9-12 weeks of age were isolated and artificially perfused. The protocol included: 30 min stabilization period, 30 min global no flow ischemia, 15 min fatty acid infusion with reperfusion, and 75 min reperfusion in the absence of fatty acids. The fatty acid infusions included 10, 20, 40, 60, 80, 100 or 120 µM of either palmitate or DHA complexed to 3% essentially fatty acid free bovine serum albumin as well as a vehicle control. Heart functional data was recorded continuously and total heart infarct volume was determined after staining with triphenyltetrazolium chloride. DHA at 10µM significantly reduced the infarction area at the end of the reperfusion period compared to that observed in the10µM of palmitate and vehicle control conditions. Infarction areas after infusions with DHA or palmitate were similar to controls after 20-60 µM infusions and greater than controls after 80-120 µM infusions, except for the 100 µM palmitate conditions which were similar to the low and high doses. In this model of infusion, 120 µM of fatty acid was the maximum amount of DHA tolerated, as several hearts went into fibrillation and did not recover and failed to complete the reperfusion at concentrations greater than 120 µM of DHA. DHA and palmitate also exerted dose dependent effects on functional parameters. In summary, infusion of DHA and palmitate cause dose dependent effects on heart function.

Thesis (M.P.H.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 13).

Thesis (M. Sc.)--York University, 1998. Graduate Programme in Exercise and Health Science. / Typescript. Includes bibliographical references (leaves 187-215). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pMQ27389.

This thesis aimed to investigate the benefit of game-based dual-task recumbent bicycle (DT-RC) training among older adults. In addition, the thesis examined the change in cardiac fitness over an 8-week training program. Eleven healthy older adults (70-80 years old) were recruited and received an 8-week dual-task training program; combines a recumbent bicycle with interactive cognitive video games. Outcome measures were collected pre and post the intervention and included measures to assess COP for core balance, spatial-temporal gait variables, performance in visual tracking and cognitive games, neuropsychological tests and HR to workload ratio. Results showed a significant improvement in COP excursion, head tracking and success rate for cognitive games, trails making test and HR to workload ratio decreased by 44%. No significant effects were found for spatial-temporal gait variables. This study shows that the DT-RC program has beneficial effects on dual-task functions and cardiac fitness among healthy older adults.

Heart development has been extensively studied in numerous organisms throughout the twentieth century. The timing of key inductive signals and the expression of many critical transcription factors have been mapped across a variety of model systems. A collective image of the various stages of cardiac development is beginning to emerge. Although most of the seminal events are conserved across evolution, it is increasingly clear that subtle differences can have substantive effects on models of heart development processes. Furthermore, the overwhelming majority of work contributing to these models has been performed on a gene-by-gene basis. As a result, we have a loosely stitched cross-evolutionary view of cardiogenesis that leaves much to be desired by way of completeness. Thus, in order to move toward a comprehensive model of heart development, we have a critical need for global network views of heart development processes conducted within one species.Cardiac myogenesis, the development of heart muscle cells, is the earliest heart development process and is required for the formation of all adult heart structures. Key signaling pathways, and their precise timing and targets, have only recently begun to be defined. The downstream targets of these pathways and their timing of activation or repression remain largely unknown. To address this, I compiled data from three genomic microarray studies, each addressing a distinct aspect of cardiac myogenesis signaling and expression, to construct a global preliminary network of the primary inductive signals and their downstream targets in the chick model embryology system.The preliminary cardiac myogenesis network obtained from these studies generates far too many hypotheses to test experimentally. The challenge that lies ahead for elucidating the fine structure of this, or any network model, is in determining the next most enlightening experiments. Headway in sorting out more profitable experiments can be made by selecting from among the universe of known interaction data as well as taking advantage of a property selected for throughout evolution - robustness. Network robustness is loosely defined as the ability of a network to maintain input and output properties in the face of perturbation. It is unsurprising that evolution would sculpt such a characteristic into molecular networks required to perform a task in varied environmental and genetic circumstances. However the way in which evolution has engendered this quality has opened the door to an exciting new avenue for in silico experimentation.I present in this dissertation the beginnings of a collaborative project for biological network elucidation software called BioNET. The long-term goal of BioNET is to take a description of a network model and phenotype as input and return a set of candidate network models capable of more robustly producing the phenotype. Fundamental to BioNET is the ability to acquire information from the universe of known molecular interaction data for in silico experimentation in any model system. To this end, I redesigned BioNetBuilder, open-source network integration software, to transfer any and all publicly available interaction data across species and serve them via the web. As these data grow in scale, BioNET will be increasingly useful for identifying the more plausible, among possible network architectures, such as the preliminary cardiac myogenesis network presented in this dissertation.

Previous research suggests that spouse factors contribute to the course and outcomes of cardiac illness. The present study examined spouse confidence in patient efficacy, spouse psychological distress, and spouse involvement in the research project as predictors of patient participation in Phase-II cardiac rehabilitation (CR) and subsequent changes in patient health and weekly exercise in a sample of 128 cardiac patients. Spouse confidence in patient efficacy predicted the number of CR sessions attended by male patients, independent of patients' own self-efficacy ratings, and spouse psychological distress predicted CR program completion among female patients, independent of patients' own distress. Spouse confidence also independently predicted increases in male and female patients' weekly exercise at six-month follow-up. Patients whose spouses participated in the study attended more CR exercise sessions and were more likely to complete the CR program than patients whose spouses did not take part in the study. Spouse involvement in the study also predicted positive health change at six-month follow-up among female patients. Results provide preliminary evidence that spouse factors can have predictive utility in the context of Phase-II CR, and contribute to research on the behavioral pathways via which psychosocial factors are linked to cardiac health outcomes.

The long-term survival of heart transplants is limited by the development of allograft vasculopathy (AV), a vascular pathology that develops in spite of the use of modern immunosuppressive therapies. Although it is widely accepted that T cells play a major role in the development of AV, the contribution of B cells and antibody has been less well characterized. A fully MHC-mismatched cell transfer model was used to mimic the antigenic stimulus of a cardiac graft, we examined the production of antibody under conditions of clinically relevant immunosuppression in the form of the calcineurin inhibitor cyclosporine A (CyA). Anti-donor antibody with the capacity to mediate complement-dependent cytotoxicity of donor strain cells, but not third-party cells, developed in the presence of two different doses of CyA (30 mg/kg and 50 mg/kg). When this antibody was passively transferred into immunodeficient B6.RAG1-/- abdominal aortic graft recipients, the antibody alone had the capacity to mediate formation of a neointimal lesion and induce the loss of medial smooth muscle cells. These are two hallmark characteristics of AV in this animal model. A wild-type model, where BALB/c grafts were transplanted into B6 recipients and received daily CyA immunosuppression was used to test the de novo antibody response to the transplant itself. Again, anti-donor antibody was produced with the capacity to mediate complement-dependent cytotoxicity of donor cells. In addition, grafts showed evidence of C4d deposition in the medial area, indicating that area as a sit of antibody binding and activation of the classical complement cascade. The presence of anti-donor antibody has been demonstrated to correlate with poorer graft outcome and a higher risk of developing AV in patients. Examination of human epicardial coronary artery tissue from patients with cardiac transplants demonstrated the presence in the adventitia of ectopic lymphoid structures (ELS) containing CD20+ B cells, plasma cells, IgM, and IgG. These findings illustrate active, antibody-producing ELS in close proximity to the vessels developing AV. Of note was the finding of CD20+CD27+ memory B cells in these ectopic lymphoid structures. Memory B cells are rapidly re-activated following exposure to their cognate antigen and easily differentiate into plasma cells. Taken together, these data suggest that memory B cells and antibody may be contributing to long-term allograft rejection and therapeutic options should be considered to target these immune mechanisms.

Introduction: Cardiac hypertrophy is an adaptive response to increased myocardial workload that becomes maladaptive when hypertrophied hearts are exposed to an acute metabolic stress, such as ischemia/reperfusion. Acceleration of glycolysis occurs as part of the hypertrophic response and may be maladaptive because it enhances glycolytic metabolite accumulation and proton production. Activation of AMP-activated protein kinase (AMPK), a kinase involved in the regulation of energy metabolism, is proposed as a mechanism for the acceleration of glycolysis in hypertrophied hearts. However, this concept has not yet been proven conclusively. Additionally, several studies suggest that AMPK is involved in hypertrophic remodeling of the heart by influencing cardiac myocyte growth, a suggestion that remains controversial. Hypothesis: AMPK mediates hypertrophic remodeling in response to pressure overload. Specifically, AMPK activation is a cellular signal responsible for accelerated rates of glycolysis in hypertrophied hearts. Additionally, AMPK influences myocardial structural remodeling and gene expression by limiting hypertrophic growth. Experimental Approach: To test this hypothesis, H9c2 cells, derived from embryonic rat hearts, were treated with (1 µM) arginine vasopressin (AVP) to induce hypertrophy. Substrate utilization was measured and the effects of AMPK inhibition by either Compound C or by adenovirus-mediated transfer of dominant negative AMPK were determined. Subsequently, adenovirus-mediated transfer of constitutively active form of AMPK (CA-AMPK) was expressed in H9c2 to specifically increase AMPK activity and, thereby, further characterize the role of AMPK in hypertrophic remodeling. Results: AVP induced a metabolic profile in hypertrophied H9c2 cells similar to that in intact hypertrophied hearts. Glycolysis was accelerated and palmitate oxidation was reduced with no significant alteration in glucose oxidation. These changes were associated with AMPK activation, and inhibition of AMPK ameliorated but did not normalize the hypertrophy-associated increase in glycolysis. CA-AMPK stimulated both glycolysis and fatty acid oxidation, and also increased protein synthesis and content. Howver, CA-AMPK did not induce a pathological hypertrophic phenotype as assessed by atrial natriuretic peptide expression. Conclusion: Acceleration of glycolysis in AVP-treated hypertrophied heart muscle cells is partially dependent on AMPK. AMPK is a positive regulator of cell growth in these cells, but does not induce pathological hypertrophy when acting alone.