Improved success of paediatric cardiac transplantation has resulted in increased survival of recipients into young adulthood (19 to 29 years of age). Young adults who received a heart transplant during childhood have experienced multiple life sustaining procedures. As survival and longevity increase, it is clear that transplant recipients experience negative physiological, psychological and social sequelae. With heart transplant offering individuals a chance to extend life into young adulthood, recipients need lifelong care and at age 18 they will transition from paediatric to adult healthcare facilities. The study addressed young adults circumstances of existence and their competing interests within various social environments. This research project applied Pierre Bourdieu’s theoretical concepts of habitus, field and capital, to conceptualize and engage with empirical knowledge production about young adults who have received a heart transplant during childhood. Using visual methodology, focused open-ended interviews were conducted with 12 young adults who had a heart transplant during childhood. Bourdieu’s work provided a theoretical framework to investigate transplant recipients’ identities and social repositioning in relation to dominant discourses of organ transplant and shifting relationships with health services providers. This study involved an iterative process to identify recipients’ encounters and new compositions in relation with others, in order to answer the research objective. These findings highlight that young adult transplant recipients struggle with relational dispositions that excludes them from various fields of social engagement; their struggle and exclusion from various fields is symbolic and is embedded in the structure of the dominant social order of the field from where they become excluded; the social order is taken up and embodied, leading young transplant recipients to practices of accommodation and “normalization”. Changes in healthcare practices, attuned to person implications and peer relationships can begin to address young transplant recipients’ contradictory social positions. Such an approach can potentially lead to improvement in ongoing care and services for young adults who require a lifetime of care. At the same time, it will allow nurses to better prepare and counsel young individuals who are preparing for a heart transplant.

Improved success of paediatric cardiac transplantation has resulted in increased survival of recipients into young adulthood (19 to 29 years of age). Young adults who received a heart transplant during childhood have experienced multiple life sustaining procedures. As survival and longevity increase, it is clear that transplant recipients experience negative physiological, psychological and social sequelae. With heart transplant offering individuals a chance to extend life into young adulthood, recipients need lifelong care and at age 18 they will transition from paediatric to adult healthcare facilities. The study addressed young adults circumstances of existence and their competing interests within various social environments. This research project applied Pierre Bourdieu’s theoretical concepts of habitus, field and capital, to conceptualize and engage with empirical knowledge production about young adults who have received a heart transplant during childhood. Using visual methodology, focused open-ended interviews were conducted with 12 young adults who had a heart transplant during childhood. Bourdieu’s work provided a theoretical framework to investigate transplant recipients’ identities and social repositioning in relation to dominant discourses of organ transplant and shifting relationships with health services providers. This study involved an iterative process to identify recipients’ encounters and new compositions in relation with others, in order to answer the research objective. These findings highlight that young adult transplant recipients struggle with relational dispositions that excludes them from various fields of social engagement; their struggle and exclusion from various fields is symbolic and is embedded in the structure of the dominant social order of the field from where they become excluded; the social order is taken up and embodied, leading young transplant recipients to practices of accommodation and “normalization”. Changes in healthcare practices, attuned to person implications and peer relationships can begin to address young transplant recipients’ contradictory social positions. Such an approach can potentially lead to improvement in ongoing care and services for young adults who require a lifetime of care. At the same time, it will allow nurses to better prepare and counsel young individuals who are preparing for a heart transplant.

No description available.

In previous studies on heartbeat series, it has been proposed that the healthy heartbeat pattern represents complex nonlinear dynamics, and such cardiac nonlinearity may be used as a clinical indicator for the diagnosis of certain types of heart disease. However, it is still not quite clear whether there is any difference among the heartbeat series of patients with congestive heart failure (CHF), or whether cardiac nonlinearity represents a severe heart disease situation. In the present study, parallel cascade identification (PCI), which frequently requires only short stretches of data to obtain highly promising results, is used to distinguish severe congestive heart failure, a clinical situation associated with a high-risk of sudden death, from low-risk CHF. Parallel cascade identification is an accurate and robust method for identifying dynamic nonlinear systems. The PCI algorithm combined with a specified statistical test may be used as a severe congestive heart failure marker by comparing a nonlinear model with a “linear” model (more precisely, a first-order Volterra series). In this thesis, PCI is applied to distinguish R-R wave intervals of CHF patients who died from those of patients who survived in a 5-year study. The detection accuracy of the PCI detector is evaluated over a first set of 49 patients, and then over a larger set of a further 352 patients, and consistent results are obtained between the two sets. Over the larger set, Matthews' correlation coefficient of nonlinearity with unfavorable outcome (death) is , sensitivity for predicting unfavorable outcome is , while the specificity is . The R-R wave interval exhibits nonlinearity in patients who died during the 5-year study. However, typically nonlinearity cannot be detected in patients who survived during the study. These findings show that for patients with congestive heart failure, nonlinearity is associated with unfavorable outcome (death), while patients for whom nonlinearity cannot be detected overwhelmingly have good outcomes. This is significant for clinical diagnosis and prognosis of severe congestive heart failure. / Thesis (Master, Electrical & Computer Engineering) -- Queen's University, 2007-09-28 11:54:57.695

Heart failure (HF) is a prevalent disease in society which is associated with decreased cardiac output. This thesis describes the proteomic analysis of cardiac tissue obtained from HF patients and a transgenic animal model of HF. Initial experiments optimized one proteomic technology, 2-dimensional gel electrophoresis (2-DE), to maximize the number of proteins which could be observed / resolved from human cardiac tissue. Protein abundance changes in cardiac tissue between normal patients and those with a diagnosis of ischemic cardiomyopathy were determined by performing 2-DE and identifying proteins by mass spectrometry. HF patients had a reduced abundance of proteins involved in energy production and the sarcomere. Sarcomeres contain the myofilament subproteome consisting of thick and thin filaments with the thick filaments primarily myosin. Thick and thin filament undergo Ca2+ induced ATP hydrolysis to form crossbridge cycles, resulting in muscle contraction. An assembly chaperone for myosin, UNC-45B, was found to be increased in HF patients. Western blot analysis confirmed that the abundance of UNC-45B was increased in different etiologies of heart failure. Follow up physiological measurements demonstrated that UNC-45B is most likely a protein necessary for transcriptional control of the α-isoform of myosin heavy chain. In a second proteomics study, abundance changes occurring in a pacing induced model of HF in wild-type (WT) and transgenic (TG) rabbits with increased expression of the α-isoform of myosin heavy chain were examined. WT and TG rabbits had a different response in their myofilament and intermediate filament abundance changes following induction of HF. TG rabbits had a decreased abundance of heat shock proteins and non-sarcomeric associated desmin. As well, TG rabbits had an increased ratio of actin:myosin heavy chain and UNC-45B suggesting an altered ratio of thick to thin filaments. In conclusion, an altered abundance of contractile proteins, regulated in part by UNC-45B, may be one cause of the contractile dysfunction which occurs in HF. / Thesis (Ph.D, Physiology) -- Queen's University, 2007-12-21 09:19:45.172

In patients with normal hearts, increased vagal tone is associated with the onset of paroxysmal atrial fibrillation (AF). Vagal denervation of the atria renders AF less inducible. Circumferential pulmonary vein ablation (CPVA), with or without isolation (CPVI), is effective for treating paroxysmal AF, and has been shown to impact HRV indices, in turn reflecting vagal denervation. We examined the impact of CPVI on HRV indices over time, and evaluated the relationship between vagal modification and rate of recurrence of AF. High resolution ECG recordings were collected from 64 patients (49 male, 15 female, mean age 57.1±9.7) undergoing CPVI for paroxysmal (n=46) or persistent (n=18) AF. Recordings were made pre-procedure, and at intervals up to 12 months. Success was defined as no recurrence. After CPVI, 27 patients presented recurrence. Pre-procedure HRV variables did not differ from controls in patients with a subsequent successful procedure. However, patients with recurrence demonstrated significantly-reduced pre-procedure HRV compared both with controls, and with patients having successful procedures (39.6±23.4 & 33.7±19.2 vs 21.8±11.8, P =0.01 & P=0.04). Following the procedure, HRV was reduced vs pre-procedure in patients with successful procedures (33.7±19.2 vs 18.6±15.8, P=0.01), and did not differ from unsuccessful procedures over a 12 month FU. Both groups were reduced compared with a control value. There was no significant difference in HRV between patients who experienced recurring AF (n=9), and those who experienced AT or flutter (n=18). Our data suggests that patients experiencing recurrence after one procedure have reduced HRV that is not changed by CPVI; whereas patients with a successful single procedure experience a change in HRV variables that is sustained over a long period, but is no different post-procedure from patients experiencing recurrence. These data suggest that denervation associated with CPVI may benefit patients with normal vagal tone prior to the procedure, but that sustained denervation is not a critical factor in successful outcome after CPVI. / Thesis (Master, Computing) -- Queen's University, 2010-12-07 08:32:15.066

No description available.

Alcohol abuse is the second most prevalent lifetime psychiatric disorder. However, individuals do not face an equal risk of developing problematic alcoholrelated behaviors. Alcohol use disorders are heterogeneous conditions whose development may be caused by a variety of factors and vulnerabilities. The identification of markers of risk is necessary in order to identify individuals at higher risk for addiction early on as well as to help develop treatment interventions which target an individual's specific risk factors. The goal of the present dissertation is to increase our understanding of the role that one putative risk factor, an exaggerated cardiac response to alcohol, may play in the development of addictive behaviors. Five studies are reported. / The first study revealed that an exaggerated heart rate response to alcohol is associated with subjective reports of increased alcohol-induced stimulation. In a second study, the relationship between the cardiac response to alcohol and personality characteristics was examined. Individuals who demonstrated the elevated cardiac response to alcohol displayed a distinct personality profile characterized by high sensation-seeking and sensitivity to reward. Two separate studies followed investigating the relationship between this physiological response to alcohol and other addictive behaviours. One study found that individuals with an exaggerated cardiac response to alcohol were more likely to obtain superior scores on a measure of pathological gambling, while the next study found that users of psychostimulants (e.g., cocaine) also displayed heightened alcohol-induced cardiac responses. A final study examined the impact of conditioned cues of reward and non-reward on alcohol-induced cardiac responses. Individuals who had previously displayed elevated cardiac responses to ethanol showed reduced cardiac reactivity when alcohol ingestion occurred in a non-rewarding environment. Overall, these findings suggest that the cardiac response to alcohol is a marker of a pathway that may lead to addictive behaviors through increased sensitivity to incentive reward.

ABSTRACT To understand the mechanisms underlying cardiac dysfunction during ischemia reperfusion (I/R) injury, we tested the hypothesis that oxidative stress and defects in endothelium play a critical role in the activation of calpain and matrix metalloproteinases (MMP), inhibition of sarcolemmal (SL) Na+-K+-ATPase, and induction of cardiac dysfunction during I/R injury. It was observed that I/R induced depression in cardiac function and SL Na+-K+-ATPase activity was greater in hearts perfused at constant flow than in hearts perfused at constant pressure. Such a difference was associated with increased calpain activity as well as decreased endothelial nitric oxide synthase protein content and in nitric oxide production. The depression in Na+-K+-ATPase activity and decrease in protein content of Na+-K+-ATPase isoforms in I/R hearts were associated with an increase in calpain activity and translocation of calpain isoforms (I and II) from the cytosol to SL membrane as well as changes in the distribution of calpastatin. I/R induced alterations were Ca2+-dependent and were prevented by treatment with calpain inhibitors, MDL28170 and Leupeptin (Leu). These results suggest that depressions in cardiac function and SL Na+-K+-ATPase activity in the I/R hearts may be due to endothelial dysfunction as well as changes in the activity and translocation of calpain. In another set of experiments, we examined the role of oxidative stress in activation of calpain during I/R and its association with changes in the activity of MMP. Our results show depression of cardiac function and Na+-K+-ATPase activity in I/R hearts were associated with increased calpain and MMP activities. These alterations due to I/R were attenuated by ischemic preconditioning as well as treatment with antioxidant, N-acetylcysteine (NAC) and mercaptopropionylglycine (MPG). Treatment of I/R hearts with MMP inhibitor doxycycline (Dox) improved I/R-induced changes in cardiac function and Na+-K+-ATPase activity without affecting the calpain activation while treatment with calpain inhibitors, Leu and MDL 28170, reduced the MMP activity significantly in addition to attenuating the I/R-induced depression in Na+-K+-ATPase activity. These results suggests that alterations in Na+-K+-ATPase activity in I/R hearts are associated with oxidative stress and intracellular Ca2+ overload induced activation of calpain and MMP.

No description available.