Wall shear stresses are thought to have an influence on the formation of deposits of blood fats on the linings of the arteries, in atherosclerosis. Measuring velocities close to an artery wall to determine wall shears is difficult in view of the thinness of the boundary layer. Analytical solutions are limited to simple geometries and numerical analyses of three-dimensional, unsteady blood flows are expensive in terms of computational time. In the present study, finite element analyses of blood flow in models representative of the human aorta are based on two-dimensional sections in order to reduce the computational requirement.

Thesis submitted in fulfilment of the requirements for the degree Masters of Technology: Radiography in the Faculty of Health and Wellness Sciences at the Cape Peninsula University of Technology / BACKGROUND: Diabetic patients are at increased risk of cardiovascular events and stroke, and its prevention is therefore the desired goal. In the arsenal of available techniques, ultrasound plays a vital role in primary healthcare. It is reliable, cost-effective and a noninvasive diagnostic tool that may prove beneficial for screening individuals at risk of cardiovascular disease (CVD) and stroke in SA. OBJECTIVE: To determine the interrelationships between carotid ultrasound findings with glycaemia status and contributing risk factors of atherosclerosis in the selected population. METHODS: Initially blinded by the glycaemia status, blood results, contributing risks and patient demographics, both carotid arteries were evaluated with duplex ultrasound (DUS), during July 2010 – July 2011. Using graphs, figures, frequency tables, means and standard deviations for the selected study population, univariate, multivariate and stepwise regression analysis was done to determine the association between ultrasound findings and risk factors for atherosclerosis. The hypothesis tested in this study was to determine if there is an increased incidence of carotid artery intima-media thickening (CIMT), plaque formation and stenosis in patients diagnosed with T2DM and hyperglycaemia in a very specific sub-population of mixedancestory, residing in Bellville South Africa (BSA). RESULTS: Of 534 subjects, 375 were of mixed ancestry and ≥35yrs of age, which met the inclusion criteria for the carotid ultrasound substudy. The glycaemic status for each individual was established, and 44% (165/375) were diagnosed hyperglycaemic, of which 66.7% (110/165) were diabetic (T2DM) and 33.3% (55/165) were pre-diabetic (Pre-DM). Majority (56%:265/375) had a normal glycaemic status. The ultrasound measurement of the carotid wall thicknesses (Mean Rt. and Lt. CIMT) revealed a statistically significant rise from normal glycaemia status to DM status for both the males (p = 0.0115*; p = 0.0259*) and females (p < 0.0001**; p < 0.0001**) respectively. In terms of plaques and internal carotid artery (ICA) stenosis (124/375), when grouped into normal and hyperglycaemic sub-groups, indicated plaque presence and some form of narrowing. A <50% stenotic ratio noted in 61% (76/124) of the hyperglycaemic group, that was 1.6 times higher than those with normal glycaemia (48/124). Predisposing factors demonstrated significantly higher levels in the females than in the males. The univariate multiple regression analysis after adjusted R² of 0.3247 for all independent variables (predisposing /contributing risk factor markers) of age (yrs.), SBP (mmHg), hs-CRP (mg/L), S-Cotinine (ng/mL) and LDL (mmol/L) showed statistically significant positive associations with dependent variable of the mean carotid wall thickness (p < 0.0001**, p< 0.0001**, p = 0.0033*, p = 0.0409* and p = 0.0044)* respectively. Statistically significant positive differences and standard error (SE), for every unit of change (1yr.) of age (yrs.), as a contributing factor for herosclerosis, there was a change in the mean carotid wall thickness as predicted according to this model. The total contribution of independent risk factors to CIMT ultrasound measurements were calculated as 34.5% (Adjusted R² = 0.3247). In the multivariate stepwise regression analysis, the independent variables of age (p< 0.0001) ** and systolic blood pressure (p < 0.0001) ** showed the strongest positive association with carotid wall thickeness changes. The hs-CRP (mg/L) inflammatory markers (p = 0.0014)* and LDL (mmol/L) (p = 0.0208)* were the 2nd and 3rd highest positive associated contributory risk factors for carotid artery wall thickening. The hip circumference (p = 0.0008)* and waist circumference (p = 0.0 555) + risk factors related to obesity was significant and approached significance, respectively, with the predicted increase of carotid artery wall thickening. CONCLUSION: Subjects diagnosed with T2DM and hyperglycaemia had increased levels of CIMT, plaques and carotid artery stenosis, compared to those subjects without T2DM. Age and systolic blood pressure, inflammatory (raised hs-CRP) and LDL cholesterol changes, and central (truncal) waist circumference adiposity, were positively associated with increased carotid intima media thickness. Smoking (S-Cotinine) and gender also reflected a direct relationship with CIMT changes. The hip circumference adiposity and diastolic blood pressure measurements were not directly associated with an increase in CIMT, which are in keeping with hypertension and obesity formulas. These findings confirm the association of thickened CIMT, plaques and stenosis with ‘unhealthy’ T2DM subjects at higher risk of CVD and stroke. The total contribution of independent risk factors to CIMT measurements were calculated as 34.5% (Adjusted R² =0.3247). The gathered information, discussion of results, and concluding statements thereby supports the recommendation of carotid artery ultrasound evaluation, for screening and diagnosis in primary health care, for ‘flagging’ high risk individuals at risk of stroke, so that lifestyle changes and appropriate management is early adopted.

M.Cur. (Intensive General Nursing) / The rehabilitation of the coronary artery bypass patient should be a continuation of the contact which exists during the hospitalisation phase, with specific reference to the pre-dismissal phase. As a member of the health team, the nurse makes the most important inputs during this phase because she is the one who is in constant contact with the patient and his family. The purpose of this study is to determine, by means of set criteria and within a nursing perspective, the contributions that are made by various support groups to the rehabilitation of persons who have undergone coronary artery bypass surgery.

M.A. (Clinical Psychology) / This research was undertaken in an attempt to validate the hypotheses that depression reported after coronary artery bypass grafting could be attributed to cognitive distortion, learned helplessness and loss of appropriate social reinforcement. Thirty subjects from the J.G. Strijdom Hospital in Johannesburg were randomly selected from a population of 80 patients who had undergone their first coronary artery bypass graft and assessed for depression and the related dimensions of the hypotheses. Mood was also assessed. On the basis of Beck Depression Inventory scores, 17 subjects were divided into experimental and control groups of depressed and non- depressed patients. The differences between the two groups were then compared. Overall, no support was found for the learned helplessness, cognitive distortion or loss of social reinforcement hypotheses, although fatigue, sadness and egotism were found to be the most significant differences between depressed and non-depressed post-operative patients. Contrary to indications in the literature, only 40 percent of patients in this study were found to be clinically depressed. The findings of this research may be seen to offer support for the "coronary-prone Behaviour" hypothesis, suggesting post-operative psychotherapeutic programmes for coronary artery bypass graft patients should address themselves to changing the behavioural styles of these patients both pre- and post-operatively.

Percutaneous coronary intervention with stent deployment is the dominant form of revascularisation for patients with coronary artery disease. Although drug-eluting stents have reduced the incidence of instent restenosis, they are associated with late problems related to delayed vascular healing including late stent thrombosis. The use of gene-eluting stents offers the potential to deliver localised gene therapy to the vascular wall with the aim of both reducing restenosis and promoting endothelialisation. Two candidate genes were investigated. Connective tissue growth factor (CTGF) promotes smooth muscle cell apoptosis and stimulates endothelial growth in vitro, and has an integral role in wound healing. Fibromodulin (FMOD) is involved in collagen metabolism and is a key mediator of scarless wound healing. Both genes have previously been shown to suppress restenosis in an ex vivo vein graft model. Plasmids containing these two genes were constructed with an expression cassette specially designed to maximise transgene expression in vascular smooth muscle cells. These plasmids were coated onto coronary stents with a polymer and the effects of these gene-eluting stents were investigated in an in vivo pig coronary artery model. Previous work by our group has suggested that systemic -blockade can affect the degree of transgene expression from viral vectors, and experiments were also performed to investigate the effect of β-blockers on plasmid-mediated gene expression. At 28 days there was no significant difference in angiographic late loss or neointimal hyperplasia between the groups treated with stents coated with FMOD or CTGF and the group treated with stents coated with the marker gene lacZ. This lack of efficacy appeared to be as a result of extremely poor transgene expression rather than due to a genuine failure of the transgenes to elicit a relevant biological effect. There was no difference in in vivo gene expression demonstrated as a result of β-blockade, but again this result was probably due to limited transgene expression. The potential causes of poor transgene expression in this study are reviewed and future directions for research on plasmid-mediated gene therapy are considered.

The first genetic CAD risk locus to be identified by genome-wide association studies, single nucleotide polymorphisms (SNPs) at 9p21.3 predispose to increased risk of CAD. By bioinformatics scan analysis of the 9p21.3 locus; we interrogated the 59 linked SNPs over the 53,202bp to identify putative transcription factor-binding consensus sequences. We hypothesize that some genetic polymorphisms at the 9p21.3 locus are functional and will disrupt specific regulatory sequences within enhancers. Here, I investigated how polymorphisms affect TEAD-dependent regulation at the 9p21.3 locus, and also how polymorphisms affect GATA factor-dependent regulation at the 9p21.3 locus, using cultured HEK293 and primary human aortic smooth muscle cells (HAoSMCs) to transfect the pGL3-promoter plasmid constructs containing the reference or risk variant sequences (rs10611656, rs4977757, rs10757269, rs9632885). We showed by luciferase reporter assay that the risk allele of the SNPs disrupt activation by various TEAD transcription factors. We also performed electrophoretic mobility shift assay (EMSA) to test for allele-specific transcription factor binding that affect the family of TEAD transcription factors and the GATA factors. EMSA showed binding of TEAD3 and TEAD4, and differential binding for both GATA genotypes, and luciferase reporter assay confirmed that TEAD3 and TEAD4 activate the non-risk but not the risk allele, and for GATA factors no significant activation was shown. Our investigations lead us to conclude that rs10811656 and rs4977757 are functional and disrupt specific TEAD regulatory sequences within enhancers

Toxicity preventing activity (TxPA) is a recently identified substance in serum which counteracts the toxic effect of very low density lipoproteins upon endothelial cells in vitro. In two clinical studies, TxPA was low in individuals with angiographically demonstrable coronary artery disease. An atherogenic index which combines TxPA with lipoprotein cholesterol values classifies individuals with coronary artery disease with an accuracy of greater than 93%. TxPA precipitates with 0.15 M trichloroacetic acid and above 3 M (NH4)2SO4. Activity is present in Cohn fractions IV4 and V and is stabilized by antioxidants. TxPA co-lutes with the albumin peak on gel filtration chromatography and as a subcomponent of albumin on ion-exchange chromatography. Isoelectric focusing resolves albumin into two major peaks with pI values of 4.8 and 5.6. The TxPA is identified as the pI 5.6 albumin peak.

This report demonstrates the utilization of a new serum factor, Toxicity Preventing Activity (TxPA) in the diagnosis of coronary disease prone individuals. Our laboratory has recently identified TxPA, which offsets the toxicity of very low density lipoproteins (VLDL) upon arterial cells in vitro. In the present study, we measured TxPA activity and serum lipoprotein levels in 73 individuals undergoing coronary angiography. Serum from control subjects demonstrated 270% more TxPA than aged matched individuals with angiographically demonstrable coronary disease (CHD). When TxPA was combined with serum lipoprotein values, a new atherogenic index was generated which further distinguished these individuals with CHD from non-angiographed controls. These results demonstrate that TxPA is a new protective factor in coronary artery disease, and that the new atherogenic index provides for the first time an accurate classification of individuals with coronary artery disease.

Myocardial bridging is a congenital coronary anomaly with normal epicardial coronary artery taking an intra-myocardial course also described as tunneled artery. The majority of patients with this coronary anomaly are asymptomatic and generally it is a benign condition. However, it is an important cause of myocardial ischemia, which may lead to anginal symptoms, acute coronary syndrome, cardiac arrhythmias and rarely sudden cardiac death. There are numerous studies published in the recent past on understanding the pathophysiology, diagnostic and management strategies of myocardial bridging. This review highlights some of the recent updates in the diagnosis and management of patients with myocardial bridging. We discuss the role of various non-invasive and invasive diagnostic methods to evaluate functional significance of bridging. In addition, role of medical therapy such as beta-blockers, percutaneous coronary intervention with stents/bioresorbable scaffolds and surgical unroofing in patients unresponsive to medical therapy is highlighted as well.

No description available.