Infra-inguinal arterial bypass is becoming increasingly popular as a means of alleviating incapacitating symptoms of atherosclerosis and other progressive diseases affecting the arteries of the lower limb. The role of this procedure in limb salvage is controversial but an aggressive attitude is emerging from many centres. It is accepted that the majority of atherosclerotic patients have a short life expectancy but reconstructive vascular surgery has an important role to play in improving their quality of life. Progress in infra-inguinal bypass surgery has centred mainly on the development of synthetic grafts but the perfonnance of autologous saphenous vein has not been bettered in terms of longterm results and cost-effectivity. The initial experience of infra-inguinal bypass at Groote Schuur Hospital, Cape Town, is examined retrospectively with the objective of demonstrating the possible influence of patient factors and specific surgical practices on the outcome of results.

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Submitted in partial fulfilment of the requirements for the Degree of Doctor of Technology: Clinical technology, Durban University of Technology, 2011. / Surgical revascularization of the coronary arteries is a cornerstone of cardiothoracic surgery. The enduring nature of coronary artery bypass grafting (CABG) bespeaks of its history and proven efficacy. However, cerebral deoxygenation during on-pump coronary artery bypass graft surgery may be associated with adverse neurological sequelae. Advanced age and the incidence of preoperative co-morbidity in patients presenting for coronary artery bypass graft surgery increases the potential for stroke and other adverse perioperative outcomes (Murkin, Adams, Quantz, Bainbridge and Novick, 2007). It is hypothesized, that by using the brain as an index organ, interventions to improve cerebral oxygenation would have systemic benefits for cardiac surgical patients. In an attempt to predict those patients that are predisposed to cerebral complications, investigators have used neurological monitoring ie, Near infrared spectroscopy (NIRS) to enhance detection of hypoxic conditions associated with neurological injury (Hoffman, 2006). Serum S100B protein has been used as a biochemical marker of brain injury during cardiac surgery. Elevated levels serve as a potential marker of brain cell damage and adverse neurological outcomes (Einav, Itshayek, Kark, Ovadia, Weiniger and Shoshan, 2008). Aims and Objectives of the study This prospective, quantitative, interventional study was carried out to maintain cerebral tissue oxygen saturation during cardiopulmonary bypass above 75% of the baseline level by implementation of a proposed interventional protocol. The analysis of S100B which is a marker of neurological injury and optimization of regional cerebral oxygen saturation would allow for the formulation of an algorithm which could be implemented during on-pump coronary artery bypass graft surgery as a preventive clinical measure further reducing the risk of neurological injury. Central venous lines (CVP) are inserted routinely during cardiac surgery. Central venous oxygen saturation is a global marker of tissue oxygenation. A secondary aim of the study was to determine if a correlation existed between central venous and cerebral tissue oxygen saturations. If a positive correlation existed then central venous oxygen saturation could be used as a surrogate measure of cerebral tissue oxygen saturation during on-pump coronary artery bypass graft surgery. This study is one of the first done in the South African population group. Methods Forty (40) patients undergoing on-pump coronary artery bypass graft surgery were recruited at Inkosi Albert Luthuli Central Hospital. Patients were randomized into a control group (n=20) and interventional group (n=20) using a sealed envelope system. The envelope contained designation to either group. Envelopes were randomly chosen. Intraoperative regional cerebral oxygen saturation (rSO2 ) monitoring with active display and treatment intervention protocol was administered for the interventional group. In the control group regional cerebral oxygen saturation monitoring was not visible to the perfusionist operating the heart lung machine during cardiopulmonary bypass (blinded). Recording of regional cerebral saturation was conducted by an independent person (another perfusionist) who was not involved in the management of the case so as to ensure that no interventions were carried out on the control group. Arterial blood samples for the measurement of serum S100B were taken pre and postoperatively. An enzyme immunoassay (ELISA) was used for the quantitative and comparative measurement of human S100B concentrations for both groups. Central venous oxygen saturation was monitored from the CVP using the Edwards Vigileo monitor. Cerebral monitoring constituted the use of Near infrared spectroscopy monitoring using the Invos 5100c, Somonetics Corp, Troy MI monitor. Adhesive optode pads were be placed over each fronto- temporal area for cerebral oxygen measurement. During cardiopulmonary bypass, eight time period measurements of mean arterial pressure (MAP), heart rate, temperature, activated clotting time (ACT), patient oxygen saturation (SpO2), partial pressure of carbon dioxide (pCO2), haematocrit, lactate, pH, haemoglobin (Hb), base excess (BE), potassium (K+), sodium (Na+), glucose, calcium (Ca2+), central venous oxygen saturation (ScvO2), cerebral tissue oxygen saturation (rSO2), fraction inspired oxygen (FiO2 ), sweep rate, pump flow rate (cardiac index), and percentage isoflurane per patient were taken. The time periods when data was recorded included: 5 minutes after onset of cardiopulmonary bypass, aortic cross clamping, after cardioplegic arrest, during distal anastomosis, during proximal anastomosis, during rewarming, after aortic cross clamp release and before termination of cardiopulmonary bypass. Baseline measurements were also taken. Clinical data recorded for both groups included: the number of grafts performed, cardiopulmonary bypass time, cross clamp time, red blood cells administered (packed cells), amount of adrenalin infused and total cerebral desaturation time. A prioritized intraoperative management protocol to maintain rSO2 values above 75% of the baseline threshold during cardiopulmonary bypass was followed. Cerebral desaturation was defined as a decrease in saturation values below 70% of baseline for more than one minute. Interventions commenced within 15 seconds of decrease below 75% of baseline value. Results The results of the study show that there was a highly significant difference in the change in S100B concentrations pre and post surgery between the interventional and control groups. The intervention vii group showed a smaller increase in S100B concentration of 37.3 picograms per millilitre (pg/ml) while the control group showed a larger increase of 139.3 pg/ml. Therefore, the control group showed a significantly higher increase in S100B concentration over time than the intervention group (p < 0.001). Maximizing pump flow rates was the most common intervention used (45 times) followed by maintaining partial pressure of carbon dioxide to approximately 40 mmHg (28 times), increasing mean arterial pressure by administration of adrenalin (11 times) and administration of red blood cells to increase haematocrit (11 times). There was a highly statistically significant treatment effect within the intervention group for each of the above interventions compared with no intervention. The above mentioned interventions significantly affected right and left cerebral oxygen saturations. However, administration of red blood cells was not found to significantly increase right (p = 0.165) and left (p = 0.169) cerebral oxygen saturation within the intervention group. The study highlighted a significant difference between the intervention and control groups in terms of cerebral desaturation time (p <0.001). The mean desaturation time for the control group was 63.85 minutes as compared to 24.7 minutes in the interventional group. Cerebral desaturation occurred predominantly during aortic cross clamping, distal anastomosis of coronary arteries and aortic cross clamp release. Predictors of cerebral oxygen desaturation included, partial pressure of carbon dioxide (pCO2), temperature, pump flow rate (LMP), mean arterial pressure (MAP), haematocrit, heart rate (HR) and patient oxygen saturation (SpO2). Central venous oxygen saturation was not significantly related to right (p = 0.244) or left (p = 0.613) cerebral oxygen saturations. Therefore central venous oxygen saturation cannot be used as a surrogate measure of cerebral tissue oxygen saturation during on-pump coronary artery bypass graft surgery. viii Conclusion These findings demonstrate the positive effect of optimizing cerebral oxygen saturation using an interventional protocol on markers of neurological injury (S100B). Optimization of pump flow rate, partial pressure of carbon dioxide and mean arterial pressure would result in increased cerebral oxygen saturation levels and a reduction in neurological injury. Therefore, an algorithm incorporating these interventions can be formulated. Monitoring specifically for brain oxygen saturation together with an effective treatment protocol to deal with cerebral desaturation during on-pump CABG must be advocated.

The success of endoluminal stent-graft treatment for abdominal aortic aneurysm relies on maintenance of an effective seal when the stent expands into the healthy artery. Clinical observation of aortic neck dilation following endoluminal grafting has led to the hypothesis that excessive stent expansion forces may cause remodelling and dilation of the artery to accommodate the strong forces. This may lead to failure of the seal, hence so-called endoleak. In this research, we analysed the force field generated by aortic stent-grafts and investigated in vitro approaches for studying the effects of these forces on cells within the vascular wall. The pressure-deformation behaviour of ovine arteries was examined experimentally and was found to vary with artery type. A finite element model of abdominal aorta (AA) characterised by Mooney-Rivlin hyperelastic material properties was validated. The property inputs were derived from the polynomial form of the strain energy density function proposed by Patel and Vaishnav. Stent-artery contact simulations revealed stresses 1.2-19 times higher than within a normal vessel at 120 mmHg when contacted by a zig-zag, square cross-section stent that expanded the AA by 3-16%. Streses 1.3-23 times normal were predicted for circular cross-section stents at the same range of expansions. The stress distribution was determined to be concentrated at the contacting surface and within the inner region of the aortic wall. These results confirmed that the forces within the vessel wall are likely to place unnatural physiological demands on the cells within. We then developed an in vitro system for studying the impact of this mechanical stress on cells within a three dimensional (3D) structure. A 20 wt% poly(vinyl alcohol) (PVA) - 5 wt% collagen tubular construct was developed to support cells, and was shown to sustain physiological blood pressures. Two cell-seeding techniques were examined, direct cell encapsulation and surface cell-seeding. Both demonstrated the capability of entrapping viable cells within the construct that remained viable for up to 4 days. In conclusion, stent contact does create abnormal stress concentrations within the vessel wall with a magnitude severely higher than physiological levels. A feasible tubular construct and an in vitro system were developed, enabling further assessments on the effects of these abnormality on the cells.

Thesis (PhD)--Stellenbosch University, 2001. / ENGLISH ABSTRACT: Please refer to fulltext for abstract. / AFRIKAANSE OPSOMMING: Sien volteks vir opsomming.

For a considerable number of years the problem of revascularizing the myocardium after the development of coronary circulatory deficiency has stirred the imagination of physiologists, clinicians and surgeons. The obstruction in the coronary system brings a reduction in the coronary blood flow which is responsible for the symptoms and deterioration of the myocardial function In hearts otherwise normal or close to a standard normal state.

Introduction The long-term patency of the grafts used during the coronary artery bypass grafting (CABG) is one of the most significant predictors of the clinical outcomes. The gold standard graft used during CABG with the best long-term patency rate and the better clinical outcomes is left internal thoracic artery (LITA) grafted to the left coronary artery (LCA). The controversy lies in choosing the second-best conduit for the non-left coronary artery (NLCA) with similar patency rate as LITA. This meta-analysis examines the long-term patency and clinical outcomes of all arterial grafts versus all venous grafts used during the CABG. Methods A comprehensive literature search of all published randomized control trials (RCTs) assessing long-term patency and clinical outcomes of grafts used in CABG was conducted using PubMed, Cochrane Central Registry of Controlled Trials, and Google Scholar (1966-2018). Keywords searched included combinations of "CABG", "venous grafts in CABG", "arterial grafts in CABG", "radial artery grafts in CABG", "gastroepiploic artery grafts in CABG", "patency and clinical outcomes". Inclusion criteria included: RCTs comparing the long-term patency, and clinical outcomes of radial artery, right internal thoracic artery, gastroduodenal artery, and saphenous vein grafts used in CABG. Long-term patency of the grafts and clinical outcomes were analyzed. Results Eight RCTs involving 2,091 patients with 1,164 patients receiving arterial grafts and 927 patients receiving venous grafts were included. There was no difference between the long-term patency rate (relative risk (RR) = 1.050, 95% confidence interval (CI) = 0.949 to 1.162, and p = 0.344), overall mortality rate (RR = 1.095, 95% CI = 0.561 to 2.136, and p = 0.790), rate of myocardial infarction (MI) (RR = 0.860, 95% CI = 0.409 to 1.812, and P = 0.692), and re-intervention rate (RR = 0.0768, 95% CI = 0.419 to 1.406, and P = 0.392) between arterial and venous grafts. Conclusion The use of arterial conduits over the venous conduits has no significant superiority regarding the long-term graft patency, the rate of MI, overall mortality, and the rate of revascularization following CABG. Additional adequately powered studies are needed to further evaluate the long-term outcomes of arterial and venous grafts following the CABG.

For small diameter (<6 mm) blood vessel replacements, lack of collaterals and vascular disease preclude homografts; while synthetic analogs, ePTFE, expanded polytetrafluoroethylene, and PET, polyethyleneterephathalate, are prone to acute thrombosis and restenosis. It is postulated that the hierarchical assembly of cell populated matrices fabricated from protein analogs provides a new design strategy for generating a structurally viable tissue engineered vascular graft. To this end, synthetic elastin and collagen fiber analogs offer a novel strategy for creating tissue engineered vascular grafts with mechanical and biological properties that match or exceed those of native vessels. This work details techniques developed for the fabrication of prosthetic vascular grafts from a series of extracellular matrix analogs composed of nanofibrous collagen matrices and elastin-mimetic proteins, with and without cells, and subsequent evaluation of their biocompatibility and mechanical properties. The work details the fabrication and mechanical analysis of vascular grafts made from aforementioned protein analogs. Subesequent studies detail seeding and proliferation of rodent mesenchymal stem cells on protein-based composites to recapitulate the media of native vasculature. Finally detailing in vivo biocompatibility and stability of tissue engineered vascular grafts.