Since 1933, studies have explored the concept of trauma induced secondary cardiac injury (TISCI), yet till 2012, it had not been defined as the incidence of cardiac events and rise in cardiac biomarkers following traumatic injury. Despite, improvements in early outcomes, trauma patients have reduced long-term mortality with cardiac disease being the major contributor. Although many putative mechanisms have been suggested for TISCI, the underpinning pathophysiology still remains unclear. In this thesis, a prospective study of 290 critically injured patients identifies a 13% incidence of adverse cardiac events (ACE) with consistently raised serum h-FABP levels in these patients. H-FABP was found to be a good predictor of ACE through ROC analysis and a h-FABP of 16.8 ng/ml used to define trauma induced secondary cardiac injury (TISCI). TISCI was associated with longer hospital stay and higher mortality. Patients who developed ACE had higher plasma levels of adrenaline and noradrenaline with a correlating increase in plasma h-FABP. On multivariate analysis, hypertension was the only independent risk factors for ACE. The increase in serum cardiac biomarkers was reflected by an increase in serum h- FABP in our group's trauma hemorrhage murine models. The hearts of these models were used in the experiments that form the last experimental chapter of this thesis. Protein expression studies confirm this increase in serum h-FABP by evidence of concurrent leaching in the cardiac tissue, along with Troponin I. Myocardial injury was evident on electron microscopy with evidence of interstitial and organelle oedema, myofibrillar degeneration, nuclear condensation and changes in mitochondrial morphology. Immunohistochemistry and western blotting protein studies demonstrate the translocation of the mitochondrial death-related protein AIF to the cytosol and nucleus, where it becomes its active pro-apoptotic form. This thesis propositions the utility of the cardiac biomarker h-FABP in predicting ACE and outcomes in critically injured patients. Although increasing serum noradrenaline and adrenaline levels are associated with higher incidence of ACE and biochemical evidence of cardiac injury with rising h-FABP levels, multivariate analysis negates their value as independent predictors of ACE. Leaching out of the proteins h-FABP and Troponin I in the murine cardiac tissue confirmed the value of serum measurements of these proteins as markers of cardiac injury. This was associated with widespread ultrastructural myocardial damage in the TH mice with changes in mitochondrial morphology. The mitochondrial damage seen is associated with the translocation of the mitochondrial death-related protein AIF to the cytosol and the nucleus where I propose its canonical signaling leading to nuclear degradation and cell death is the driver of cardiac dysfunction.

End stage renal disease (ESRD) patients have an excess cardiovascular risk, above that predicted by traditional risk factor models. Despite the advances in both Cardiovascular disease (CVD) management and renal replacement therapy (RRT), there still is a major burden of cardiovascular mortality and morbidity in the chronic kidney disease (CKD) population. Declining renal function itself represents a continuum of cardiovascular risk and in those individuals who survive to reach ESRD, the risk of suffering a cardiac event is uncomfortably and unacceptably high. Pro-thrombotic status may contribute to this increased risk. Global thrombotic status assessment, including measurement of occlusion time (OT) the time taken to form an occlusive platelet rich thrombus and thrombolytic status (time taken to lyse such thrombus) as assessed by measuring Lysis Time (LT), may identify vulnerable patients. The aim of this study was to assess overall thrombotic status in ESRD and relate this to cardiovascular and peripheral thrombotic risk. Small sub studies were also planned to establish the effect of RRT modality on the thrombotic status.

Background: People from ethnic minority immigrant groups living in host countries are known to have higher risk factors for cardiovascular diseases. The role of acculturation, or assimilation into a different and dominant culture, is often studied from social and medical views when focusing on individuals diagnosed with cardiovascular diseases and their recovery after cardiac events. However, the effects of the complex roles of acculturation and religious coping on these individuals are rarely considered in the research. There is limited knowledge regarding the complex roles of acculturation and religious coping in adopting healthy lifestyle behaviours and managing stress among individuals with cardiovascular diseases from Arab communities in the Ottawa region. This research project’s general purpose was to explore and understand the complex roles of acculturation and religious coping through the experiences of individuals diagnosed with CVD from Arab communities in the Ottawa region. Objectives: The specific objectives were to 1) identify and understand the challenges among Arab immigrants related to acculturation and religiosity in adopting healthy lifestyle behaviours and managing stress; 2) measure and describe the levels of religious beliefs as well as religious coping strategies, acculturation, perceived stress, and healthy lifestyle behaviours among Arab individuals living in the region of Ottawa, Ontario, Canada who have been diagnosed with cardiac events or who are at high risk for cardiovascular diseases; and 3) explore the role of acculturation and religious coping in shaping male Arab individuals’ lived experiences after a cardiac event and to explore their ways of understanding lifestyle behaviours and cardiac rehabilitation during recovery. Methods: A mixed-method approach was adopted in this research, which included three separate studies: Study 1 was a qualitative study (views of key informants with first-hand knowledge) in which three face-to-face focus groups were conducted with 17 Arab health promoters; Study 2 was a cross-sectional survey study was conducted with 63 individuals from local Arab communities who had been diagnosed with cardiac events or who were at high risk for cardiovascular diseases; and Study 3 consisted of a phenomenographic qualitative study, semi-structured in-depth interviews with male Arab individuals (N=10), selected from Study 2, who identified themselves as having had cardiac events while living in Canada. Results: From the perspective of Arab health promoters, there was an overlapping between various aspects of acculturation and religious beliefs that may have impacted the healthy lifestyle of Arab immigrants. These challenges were coded in four themes: “Culture first!”: dominant influence of home country culture; “Religiosity alone does not make you healthy!”: limited religious influence; “It is not easy!”: difficulties adapting to the Canadian lifestyle; and “We are not young!”: generational differences in adopting a healthy lifestyle. Findings from the survey study indicated that most participants were oriented more toward their Arabic culture than Canadian culture. Participants tended to be religious, and their nutritional behaviours were healthier than physical activity behaviours. However, age, gender, and interestingly, length of time living in Canada did not affect the participants’ results in any of the questionnaires. Based on lived experiences of 10 participants in the interview study, five core themes were identified: “Stressful events or cardiac events!”: acculturative stress effects; “It was a dreamlike event!”: dismissing perceptions of cardiac events; “recognizing risk factors is not enough to avoid them”: perceived threat; religious coping outcomes: satisfaction and fatalism; Cardiac Rehabilitation programs: who refers and who participates. Conclusion: This dissertation showed that acculturation level plays an essential role in Arab immigrants’ beliefs and behaviours regarding their health status and their experiences in preventing cardiovascular diseases risk factors or in recovery after cardiac events. Religious coping seems to be a way for less acculturated Arab immigrants to manage stress and mental burdens and find internal peace and satisfaction. From the perspective of Arab health promoters, some religious or cultural beliefs may be barriers to engaging in physical activity, especially for women and older people, and these barriers may be exacerbated by acculturative stress. Religiosity may also play an essential indirect role in managing stress through socialization, family support, and the adoption of coping strategies. Arab individuals living in the region of Ottawa, Ontario, Canada, who have been diagnosed with cardiac events or who are at high risk for cardiovascular diseases may have been more religious and less acculturated in Canadian society. Their lifestyle health behaviours related to physical activity and nutrition may have been influenced by their health status, religious beliefs, and the practices or traditions of their culture of origin. Stress and mental burdens while living in Canada reflected negatively on Arab male individuals’ experiences with cardiac events. Stress was perceived as a potential cause of cardiac events and a factor leading to low self-efficacy in changing lifestyle behaviours. There is a need to promote healthy lifestyle messages and raise awareness about cardiovascular diseases risk factors among Arab communities. Future research is needed to design culturally adapted cardiac rehabilitation programs for Arab individuals and to evaluate the effectiveness of interventions with both physical and mental health components.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Background: We aimed to increase the knowledge regarding the familial arrhythmogenic disorder Long QT Syndrome (LQTS) and its recessive variant Jervell and Lange-Nielsen Syndrome (JLNS) in Sweden, including prevalences and clinical phenotypes. A specific focus was directed towards two KCNQ1 mutations –p.Y111C and p.R518X- commonly identified in Swedish LQTS index cases. Methods: Cases and families with LQTS (p.Y111C or p.R518X) and JLNS were recruited via regional clinical practices, national referrals to the Clinical Genetics laboratory, Umeå University Hospital, and a national inventory. Molecular genetics methods were used for case ascertainment. Clinical data was obtained via medical records, a questionnaire, and/or an interview. Electrocardiograms were manually assessed. In p.R518X heterozygotes intra-familial phenotypic variability (QTc and cardiac events) was assessed by analysis of sequence variants (modifier genes). The origins of the mutations p.Y111C and p.R518X were investigated using genealogical and haplotype analysis (microsatellite markers). In families sharing a common haplotype mutation age and associated prevalence was analyzed using ESTIAGE and DMLE computer software. Results: We identified p.Y111C (170 mutation-carriers) and p.R518X (101 mutation-carriers) as two major causes of LQTS/JLNS in Sweden. LQTS phenotype was revealed to be relatively benign in p.Y111C and p.R518X (annual incidence of life-threatening cardiac events, before therapy 0.05% and 0.04%, respectively). Gender-specific effects of genetic modifiers on phenotypic expression were seen. A founder origin, approximately 600-700 years ago in two northern river valleys was established for p.Y111C and p.R518X, and a high prevalence of LQTS founder descendants suggested. A minimum JLNS prevalence of 1:200 000 in preadolescent Swedish children was revealed. JLNS phenotype was mainly severe, with a cumulative incidence of life-threatening cardiac events of 53% (annual incidence rate before therapy 5%) and four sudden deaths. Possible founder effects regarding four KCNQ1 mutations; p.Y111C (8%), p.R518X (50%), c.572_576del (17%) and p.Q530X (8%) together explained 83% of the JLNS mutation-spectrum in Sweden, consisting of 8 KCNQ1 mutations. Conclusion: The high prevalence of p.Y111C- and p.R518X-related LQTS as well as JLNS revealed in Sweden could be explained by the combination of mild clinical phenotypes in heterozygotes and strong founder effects present during the population development of northern Sweden. Increased knowledge regarding the occurrence of LQTS and JLNS as well as mutation- and/or genotype-specific data constitute prerequisites for possible improvement of patient management.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

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