Abstract not available

published_or_final_version / Pharmacology / Master / Master of Philosophy

Interest in the anatomy of the coronary arteries dates as far back as the early 1500's, at a time when anatomical inquiry was being cautiously aroused. Whilst the later 1700's encouraged academic domination of anatomical study, significant documentation of the coronary arteries was only been established by the late 1800's to early 1900's. There is no doubt that this topic continues to remain dynamic, favoured for its value in applied clinical research. Indeed, technological advancement in the 21 st century has transformed modem day anatomy into more than just a simple descriptive exercise. Whether to update standard literature, create ethnically specific banks of anatomical data, abate technical difficulties associated with coronary artery surgery or provide exciting interventional possibilities for clinicians, revisiting the anatomy of the coronary arteries is clearly warranted. The objective of this investigation was to review the anatomy of the coronary arteries using a clinical approach in order to investigate the morphologic presentation of these vessels within the South African population. On a more clinically universal level, this study aimed to elucidate two focal areas of anatomical interest: extra-cardiac collaterals and myocardial bridges. The investigation was conducted by means of micro-dissection, angiography, histology and scientific evaluation. A total of 323 sets of coronary arterial patterns consisting of patient angiograms (n=212) and cadaveric dissections (n=95) were studied. Specimens were harvested at post-mortem and angiograms and surgical reports were obtained from clinical centers within KwaZulu-Natal. Results of this study confIrmed the standard anatomical description of the coronary arteries as documented. Within the South African population, the ramus marginalis artery was found to be present in 13.3% (Females: 10.7%; Males: 5.6% and Blacks: 18.0%; Indians: 6.6%; Whites: 1.4%). The LAD and LCX arteries arose from independent aortic ostia in 14.5%, (Females: 7.5%; Males: 15% and Blacks: 6.5%; Indians 50%; Whites: 35%). Right dominance was observed most frequently in 85.9% (Blacks: 82.3%; Whites: 83.6% and Indians: 86.4% and Males: 82.6%; Females: 89.2%). A bifId LAD artery was noted in 52%, (Females: 6.2%; Males: 8.7% and Blacks: 17.6%; Indians: 6.3 %; Whites: 4.5 %). In 27.7%, (Females: 24.0%; Males: 28.8% and Blacks: 29.5%; Indians: ·50%; Whites: 20%) the LCX artery failed to continue along the atrioventricular groove. The conus artery arose from a high position off the RCA in 19.2%, (Females: 16%; Males: 21% and Blacks: 19.7%; Indians: 100%; Whites: 10%); and from an independent ostium in 3.61%, (Females: 4.0%; Males: 3.8% and Blacks: 4.9% only). The LCA measured 0.82cm (0.27-2.4cm), (Females: 0.84cm, Males: 0.96cm and Blacks: 0.88cm; Indians: 0.53 cm; Whites: 0.78cm). Myocardial bridges were recorded on the RCA in 2.5% and on the LAD in 50.6%. The bridge pattern depicted myocardial loops to complete arterial investment and ranged in length from 3.0 to 20.02 mm. Scientiftc evaluation of the intramural LAD indicated positive correlation between a straight appearance ofthe LAD on angiogram and a deep myocardial position upon surgical observation (mean "tortuosity index" = 1.147 [1.373-1.045] where 1= baseline for straightness). Results were confIrmed in the correlated cadaveric investigation. Extra-coronary collaterals were observed in 100% (n=9). The arterial pattern consisted of 1 to 2 main stems with secondary anastomotic branches. The average external diameter was measured to be 0.6mm (OA-0.7mm), length 52.5mm (1883mm) with at least 5 secondary branches (3-9) of external diameter O.3mm (0.20.5mm). Results of the histopathological investigation (n=20) indicated the presence of atherosclerotic disease within the intramural LAD artery segment (15%). A 60% incidence was recorded in the pre-mural segment and 25% incidence in the post-mural arterial segments. When analysed in terms of severity, the intramural segment reflected only mild signs of intimal alteration. Although not statistically significant, mean values for coronary artery size differed between sexes. The findings were similar when evaluated in terms of the coronary artery anomalies studied. There were signifIcant differences between ethnic groups in terms of the length of the LCA. Mean values showed that Indians had the shortest LCA's when compared with Blacks and Whites. The highest incidence of the ramus marginalis branch was recorded amongst Blacks. Separate origin of the LCX and LAD was highest amongst Indians and high in comparison to reports documented in other countries. A high origin ofthe conus artery was found to be dominant amongst Blacks. A low incidence of separate origin of the conus from the aorta was recorded in the South African population. These findings are significantly lower than that reported in the literature. A right dominant system has the highest occurrence within this population. Statistical evaluation confirmed that neither sex, ethnicity, age nor height influenced dominance in a coronary arterial pattern. The presence and description of the bifid LAD has been recorded. Its occurrence is highest amongst Blacks. The anomalous path of the LCX has been documented and described. The significantly high occurrence of this disposition of the LCX within the South African population appears to be the highest reported fmd in the literature. In terms of the presence and patterns of myocardial bridges, there are no observable differences between ethnic groups or sex. Results ofthis study confirm a relationship between the straight appearance of the LAD on angiogram and its anatomical presence. Extra coronary collaterals have been successfully investigated and observed. Measurements of vessel dimensions and patterns have been recorded. Results of the histopathological investigation illustrate that the intra-mural LAD artery is relatively protected from vascular disease. It does not however support the theory that in such a sub-myocardial position, the LAD artery is never prone to the damaging effects of atherosclerosis. The "cardio-protective" effect of a muscular bridge, whilst prevalent, is dependant on the thickness and extent ofthe bridge itself The anatomy ofthe coronary arteries has been successfully documented and a bank of data, specific for a South African population has been presented. Significant aspects of coronary arterial patterns have been discussed and interpreted in terms of its clinical relevance. This study presents an original method for the investigation of EeC's using technologically advanced materials and equipment. In addition, a scientific method for confirmation of a "straight" appearance of the LAD artery has been developed in this study. Findings contribute to the bank of diagnostic indicators that may be used to predict myocardial bridges pre-operatively. Through the dissection experience of more than 150 hearts and observation of more than 200 angiograms, this study has been able to contribute to the anatomical description o fthe coronary arteries. In some ways new perspectives were afforded and on the same note, already existing concepts have been verified. The value of this study IS enhanced by the potential clinical impact that such data is envisaged to create. / Thesis (Ph.D.)-University of Durban-Westville, 2003.

Platelets have been shown to be a main contributor to thrombus formation in stenotic arteries leading to acute coronary syndromes. It is thought that increased activation and adhesion of platelets under variable shear and complex flow conditions contribute to thrombosis. The objective of this work was to evaluate the relationship between asymmetric stenosis hemodynamics and platelet adhesion using in-vitro models developed to properly simulate physiological conditions. In this study, platelet rich plasma was circulated through stenotic and straight coronary artery models. Adhesion results were obtained by post-perfusion fluorescent labelling and imaging of adhered platelets. Analysis of platelet area coverage has shown maximum adhesion occurs in the distal region of the stenosis. Most likely this is due to increased exposure time of platelets to the wall of the recirculation zone following the stenosis and that exposure being directly after a period of high shear stress. This result gives us a better understanding of the importance of both shear and flow conditions in coronary artery thrombosis.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Kardiyoloji Anabilim Dalı, 2004. / Bibliyografya var.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Kardiyoloji Anabilim Dalı, 2005. / Bibliyografya var.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Kalp Damar Cerrahisi Anabilim Dalı, 2005. / Bibliyografya var.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Kardiyoloji Anabilim Dalı, 2001. / Bibliyografya var.

Cardiovascular disease is one of the leading causes of the mortality in the western world. Many imaging modalities have been used to diagnose cardiovascular diseases. However, each has different forms of noise and artifacts that make the medical image analysis field important and challenging. This thesis is concerned with developing fully automatic segmentation methods for cross-sectional coronary arterial imaging in particular, intra-vascular ultrasound and optical coherence tomography, by incorporating prior and tracking information without any user intervention, to effectively overcome various image artifacts and occlusions. Combinatorial optimisation methods are proposed to solve the segmentation problem in polynomial time. A node-weighted directed graph is constructed so that the vessel border delineation is considered as computing a minimum closed set. A set of complementary edge and texture features is extracted. Single and double interface segmentation methods are introduced. Novel optimisation of the boundary energy function is proposed based on a supervised classification method. Shape prior model is incorporated into the segmentation framework based on global and local information through the energy function design and graph construction. A combination of cross-sectional segmentation and longitudinal tracking is proposed using the Kalman filter and the hidden Markov model. The border is parameterised using the radial basis functions. The Kalman filter is used to adapt the inter-frame constraints between every two consecutive frames to obtain coherent temporal segmentation. An HMM-based border tracking method is also proposed in which the emission probability is derived from both the classification-based cost function and the shape prior model. The optimal sequence of the hidden states is computed using the Viterbi algorithm. Both qualitative and quantitative results on thousands of images show superior performance of the proposed methods compared to a number of state-of-the-art segmentation methods.

Surgical intervention can result in endothelial denudation, driving growth factor-stimulated vascular smooth muscle cell (VSMC) migration towards the intima, leading to luminal narrowing and restenosis. Clinically approved PGI₂ analogues, including beraprost, activate the cyclic adenosine monophosphate (cAMP) signaling pathway to inhibit VSMC migration in vitro. This pathway is a potential therapeutic target, however the downstream proteins involved in the inhibitory effects of cAMP on migration remain unknown. The aims of this study were to determine the signalling pathways involved in inhibiting VSMC migration through cAMP downstream mediators, protein kinase A (PKA) and the more recently characterised exchange protein activated by cAMP (Epac), and delineate the mechanisms involved. In human saphenous vein VSMCs, Epac activation using an Epac analogue inhibited VSMC migration. Therapeutic concentrations of beraprost (1 nM) also resulted in an inhibition of VSMC migration. The use of fluorescence resonance energy transfer (FRET) confirmed 1 nM beraprost activated Epac, but not PKA. Epac is a guanine nucleotide exchange factor (GEF) for Rap1 thus Rap1 siRNA was used to inhibit the Epac pathway. This blocked the inhibitory effects of beraprost on VSMC migration. Epac1 was localised to the leading edge of migrating VSMCs. Another G-protein, RhoA, was investigated since it is essential for cell migration and is involved in several processes including actin regulation. Epac signaling inhibited PDGF-induced RhoA activation and disassembled F-actin at the leading edge, where Epac1 was previously located. This indicates that beraprost activated the Epac pathway, which inhibited RhoA to decrease VSMC migration. The clinical relevance of this study has discovered the mechanisms of Epac's inhibitory action on VSMC migration and this pathway could be targeted therapeutically to reduce restenosis. In the future the potential use of beraprost on a drug eluting stent might be beneficial to prevent restenosis formation following surgical intervention.