The aims of the present study were threefold: firstly, to further the understanding of the psychological response to heart disease; secondly, to consider the differences in the ways in which doctors and patients perceive heart disease; and thirdly, to consider how the doctor, patient, and condition interact within the illness process over a period of time. The nature of coronary heart disease (CHD) was considered, and the influence of psychological variables in CHD was discussed. Psychological factors in illness were examined, with particular emphasis on health beliefs, illness behaviour, compliance, and the doctor-patient relationship. Conclusions were drawn that to understand the illness process in heart disease, doctor, patient, and condition must be considered together, in an interactional framework. Two pilot studies were performed. The first study found that heart patients' health beliefs differed from a normal population. The second pilot study, with raised cholesterol patients, suggested the existence of five major components of the illness process: illness perception, illness effect, health orientation, doctor-patient relationship, and compliance. The main study considered groups of heart and cholesterol patients (experimental groups) and a group of general outpatients (control group), over a four-to-six month period. Patients were interviewed and given a questionnaire concerning their feelings regarding their condition. Doctors and judges also completed similar questionnaires. Results indicate that cholesterol patients rate superior coping to the other groups, and both experimental groups were higher than controls with regard to patient understanding, responsibility for health, and communication with doctor. Findings suggests alterations should be made in current conceptualization of illness behaviour. and that patient and doctor assessment of condition severity were found to be unrelated to illness behaviour. Doctor and patient perception of patient behaviour were found to be discrepant. Modifications in the treatment of heart and cholesterol patients are suggested.

Despite major advances in pharmacological and surgical treatments of cardiovascular diseases (CVDs), clinical outcomes of patients with severe CVDs remain very poor. Most of medication and interventions currently available are only playing roles of preventing further damage to myocardium, declining the risk of on-going cardiovascular events, lifting the cardiac pumping efficiency and lower early mortality rates, none of these treatments can regenerate or repair damaged cardiac tissue or restore heart function. As a result, several new strategies have been explored to overcome limitations of current therapeutic approaches. One prospective is to replace dead cardiac vascular cells with young and green cells to repair or regenerate damaged heart myocardium. Several types of stem cells, including bone marrow hematopoietic stem cells, mesenchymal stem cells (MSCs), embryonic stem cell (ESCs)and induced pluripotent stem cells (iPSCs),have been tested as the candidates for treatment of CVDs. Among a myriad of types of stem cells, bone marrow derived MSCs(BM-MSCs) has received great attention based on several unique properties such as easy isolation and expansion, stable genetic background and low immunogenicity. However, the therapeutic efficacy of BM-MSCs derived from aging or diseased donors is impaired. The differentiation potential of BM-MSCs is gradually reduced with the increased culture time. Thus, it is urgent to identify some novel alternative sources for MSCs. Moreover, the potential mechanisms of MSCs therapy have not been understood totally. This thesis is designed to investigate the therapeutic efficacy and potential mechanisms of several novel types of MSCs, including hESC-MSCs and hiPSC-MSCs and Rap1-/--BM-MSCson several types of CVDs, including pulmonary arterial hypertension (PAH), dilated cardiomyopathy (DCM)and myocardial infarction (MI). In Chapter 4, it disclosed that hESC-MSCs have a better therapeutic efficacy than BM-MSCs in attenuation of PAH induced by monocrotaline in mice. The greater therapeutic potential of hESC-MSCs on PAH was not only attributed to the higher capacity of differentiation into de-novo vascular cells, but also attributed to higher cell survival rate and greater paracrine effects post-transplantation. In Chapter 5, it demonstrated that compared with BM-MSCs, iPSC-MSCs have a better therapeutic effect on doxorubicin-induced cardiomyopathy. Several potential mechanisms of action were involved in iPSC-MSCs-based therapy for cardiomyopathy. It demonstrated that iPSC-MSCs transplantation not only attenuated the generation of reactive oxygen species(ROS)and the level of inflammation, but also restored depletion of cardiac progenitor cells and promoted endogenous myocardial regeneration against doxorubicin induced cardiomyopathy. Moreover, mitochondrial transfer and paracrine actions of iPSC-MSCs played critical roles in the rescue for doxorubicin-induced cardiomyopathy. In Chapter 6, it uncovered that compared with wild type BM-MSCs,Rap1-/--BM-MSCs transplantation achieved a better benefit to MI induced by ligation of left anterior descending (LAD)coronary artery. Rap1-mediated NF-κB activity plays a key role in regulation MSCscytokine secretion profiles. The absence of Rap1 in MSCs leads to reduced pro-inflammatory cytokines secretion and enhanced MSCs survival capacity, thus yielding a better therapeutic efficacy. In conclusion, findings presented in this thesis provide important new insights regarding different novel types of MSCs, including those derived from ESC and iPSC. They have distinct mechanisms of action from BM-MSCs and provide superior therapeutic efficacy in various form of severe CVDs, including PAH and DCM. The safety and efficacy of these novel types of MSCs for treatment of CVDs deserve further investigations. / published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

Submitted in fulfillment of the requirements for the Degree of Masters in Technology: Cardiology, Durban University of Technology, 2012. / Cardiomyopathies and their resultant heart failure (HF) remain a major cause of cardiovascular morbidity and mortality (Wood and Picard, 2004). Idiopathic dilated cardiomyopathy (IDCMO) is a primary myocardial disease of unknown cause, characterized by left ventricular (LV) or biventricular dilatation and impaired myocardial contractility. Dilated cardiomyopathy (DCMO), along with rheumatic heart disease and hypertension (HPT), is one of the leading causes of HF in Africa. In fact, in an epidemiology study of 884 patients in Soweto, IDCMO was the second major cause of HF. Thirty five percent of patients in the study, with HF, had IDCMO (Sliwa, Damasceno, Mayosi, 2005). Methodology: Patients referred to the cardiomyopathy (CMO) clinic at Chris Hani Baragwanath hospital, situated in the echocardiographic lab, were recruited, provided they satisfied the exclusion and inclusion criteria and were enrolled after obtaining voluntary informed consent. From May 2009 to September 2010, 70 patients with IDCMO were recruited for this trial. Patients with DCMO were identified by means of echocardiographic criteria which included a left ventricular ejection fraction (LVEF) of less than 45% and an end diastolic dimension (EDD) of greater than of 52 mm (2D in long parasternal axis). Results: In the present study the prevalence of left ventricular (LV) thrombus in patients with IDCMO was 18.6%. When using Univariate logistic regression, the only independent predictors of LV thrombus formation was LVEF and age. However, when multivariate logistic regression analysis was applied to the data, the only predictor with a significant association was age. The reason for this is not clear. It is postulated that perhaps younger patients have differences in the pathophysiology of their disease such as a greater smoldering inflammatory component which may therefore predispose them to thrombus formation. For example the presence of IL-6 may be important in the formation of LV clot in cases of LV dysfunction (Sosin, Bhatia, Davis, Lip, 2003). The association between LVEF and LV thrombus was borderline significant. Conclusion: The prevalence of LV thrombus formation in this cohort of patients with IDCMO was 18.6%. Echocardiographic parameters alone cannot predict which patients are more likely to develop thrombus formation. / National Research Foundation

Submitted in fulfillment of the requirements for the Degree of Masters in Technology: Cardiology, Durban University of Technology, 2012. / Cardiomyopathies and their resultant heart failure (HF) remain a major cause of cardiovascular morbidity and mortality (Wood and Picard, 2004). Idiopathic dilated cardiomyopathy (IDCMO) is a primary myocardial disease of unknown cause, characterized by left ventricular (LV) or biventricular dilatation and impaired myocardial contractility. Dilated cardiomyopathy (DCMO), along with rheumatic heart disease and hypertension (HPT), is one of the leading causes of HF in Africa. In fact, in an epidemiology study of 884 patients in Soweto, IDCMO was the second major cause of HF. Thirty five percent of patients in the study, with HF, had IDCMO (Sliwa, Damasceno, Mayosi, 2005). Methodology: Patients referred to the cardiomyopathy (CMO) clinic at Chris Hani Baragwanath hospital, situated in the echocardiographic lab, were recruited, provided they satisfied the exclusion and inclusion criteria and were enrolled after obtaining voluntary informed consent. From May 2009 to September 2010, 70 patients with IDCMO were recruited for this trial. Patients with DCMO were identified by means of echocardiographic criteria which included a left ventricular ejection fraction (LVEF) of less than 45% and an end diastolic dimension (EDD) of greater than of 52 mm (2D in long parasternal axis). Results: In the present study the prevalence of left ventricular (LV) thrombus in patients with IDCMO was 18.6%. When using Univariate logistic regression, the only independent predictors of LV thrombus formation was LVEF and age. However, when multivariate logistic regression analysis was applied to the data, the only predictor with a significant association was age. The reason for this is not clear. It is postulated that perhaps younger patients have differences in the pathophysiology of their disease such as a greater smoldering inflammatory component which may therefore predispose them to thrombus formation. For example the presence of IL-6 may be important in the formation of LV clot in cases of LV dysfunction (Sosin, Bhatia, Davis, Lip, 2003). The association between LVEF and LV thrombus was borderline significant. Conclusion: The prevalence of LV thrombus formation in this cohort of patients with IDCMO was 18.6%. Echocardiographic parameters alone cannot predict which patients are more likely to develop thrombus formation. / National Research Foundation / M

No description available.

For cardiotonic actions, DF caused a transient increase in contractility and a transient decrease in contraction rate in an isolated rat heart perfusion system. The positive inotropic effect and the negative chronotropic effect were generated by the dose-dependent inhibitions of Na+/K +-ATPase and Ca2+-ATPase respectively in rat heart homogenate. In both assays, Danshen exhibited more potent inhibitions than DF, while Fenge showed negligible inhibitory actions. / In vivo study on Spontaneously Hypertensive Rats (SHR) showed that DF could not restore the established high blood pressure to the normal level. Earlier DF treatment attenuated, but could not prevent, hypertension development. In aorta, DF improved endothelium-dependent vasodilation by potentiating acetylcholine-induced relaxation and basal nitric oxide (NO) production, and inhibiting endothelial Ca2+ATPases. Relaxation of vascular smooth muscle cells (VSMC) towards NO donors was also enhanced. For anti-oxidation, upon DF treatment, mRNA levels of superoxide dismutase (SOD), extracellular superoxide dismutase (ecSOD), catalase and glutathione peroxidase (GPx) were elevated in heart and aorta. However, studies on SOD and catalase demonstrated insignificant changes in the protein expression levels in both organs. For vasodilation, mRNA level of endothelial nitric oxide synthase (eNOS) in the aorta was upregulated, but no change on eNOS and phosphorylated eNOS (peNOS) proteins were detected. A parallel study showed that DF did not cause hypotension or improve antioxidant defense in normotensive Wistar Kyoto rats (WKY). These findings suggest the use of the Danshen and Fenge 7:3 (w/w) formulation on the comprehensive cardiovascular protection. / Previously established Danshen and Fenge 7:3 (w/w) formulation (DF) was shown to exhibit antioxidative activity by preventing oxidant-induced red blood cell hemolysis and H9c2 rat myoblast cell death in a dose-dependent manner, in which Danshen was demonstrated to be a more potent antioxidant than DF. Fenge showed no antioxidative property. The effect of in vivo ischemia-reperfusion was mimicked by the hypoxia-reoxygenation model of primary culture of neonatal rat heart cardiomyocytes. Danshen could protect cardiomyocytes against hypoxiareoxygenation damage. / Reactive oxygen species attack on cardiovascular system can lead to atherosclerosis and finally cardiac ischemia. Reperfusion, allowing the restoration of blood flow in treating atherosclerosis, in turn generates free radicals which irreversibly damage cardiomyocytes and endothelial cells. Endothelial cell damage eventually leads to hypertension. Radix Salviae Miltiorrhizae (Danshen) and Radix Puerariae Thomsonii (Fenge) have long been used together to treat various heart diseases in China. This project was focused on the antioxidative, cardiotonic and vasodilative effects of the aqueous extracts of Danshen and Fenge. / Lam Hung Ming. / "September 2006." / Adviser: Miu Yee Mary Waye. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1381. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 218-230). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

The purpose of this research was to obtain information on the content of education within cardiac rehabilitation programs, methods of administering education, what the barriers are to providing education and which professionals administer education.To reach this goal, a questionnaire was modified from a previous study and a pilot study was undertaken to establish reliability of the questionnaire. The questionnaire was then sent to a sample of 100 directors of cardiac rehabilitation programs belonging to The American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR). The questionnaire focused on 13 established areas of education within cardiac rehabilitation programs.Once the questionnaires were completed, the information was transferred to a table format based upon the 13 content areas. The following conclusions were drawn from the research and the data gathered: 11 of the 13 content areas are offered at least 84% of the time, the major barriers for the 13 content areas were lack of time and lack of interest on the patient's behalf, the most frequent methods of education for all 13 content areas were individual education, print materials, and group education, and the primary educator overall for all 13 content areas was the nurse followed by the exercise physiologist and dietitian/nutritionist. / Department of Physiology and Health Science

Indiana University-Purdue University Indianapolis (IUPUI) / Autonomic innervation of the heart begins in utero and continues during the neonatal phase of life. A balance between the sympathetic and parasympathetic arms of the autonomic nervous system is required to regulate heart rate as well as the force of each contraction. Our lab studies the development of sympathetic innervation of the early postnatal heart in a conditional knockout (cKO) of Src homology protein tyrosine phosphatase 2 (Shp2). Shp2 is a ubiquitously expressed non-receptor phosphatase involved in a variety of cellular functions including survival, proliferation, and differentiation. We targeted Shp2 in post-migratory neural crest (NC) lineages using our novel Periostin-Cre. This resulted in a fully penetrant mouse model of diminished cardiac sympathetic innervation and concomitant bradycardia that progressively worsen. Shp2 is thought to mediate its basic cellular functions through a plethora of signaling cascades including extracellular signal-regulated kinases (ERK) 1 and 2. We hypothesize that abrogation of downstream ERK1/2 signaling in NC lineages is primarily responsible for the failed sympathetic innervation phenotype observed in our mouse model. Shp2 cKOs are indistinguishable from control littermates at birth and exhibit no gross structural cardiac anomalies; however, in vivo electrocardiogram (ECG) characterization revealed sinus bradycardia that develops as the Shp2 cKO ages. Significantly, 100% of Shp2 cKOs die within 3 weeks after birth. Characterization of the expression pattern of the sympathetic nerve marker tyrosine hydroxylase (TH) revealed a loss of functional sympathetic ganglionic neurons and reduction of cardiac sympathetic axon density in Shp2 cKOs. Shp2 cKOs exhibit lineage-specific suppression of activated pERK1/2 signaling, but not of other downstream targets of Shp2 such as pAKT (phosphorylated-Protein kinase B). Interestingly, restoration of pERK signaling via lineage-specific expression of constitutively active MEK1 (Mitogen-activated protein kinase kinase1) rescued TH-positive cardiac innervation as well as heart rate. These data suggest that the diminished sympathetic cardiac innervation and the resulting ECG abnormalities are a result of decreased pERK signaling in post-migratory NC lineages.