M.Cur. / The emotional state of health of pre-operative patients about to have coronary artery bypass graft (CABG) is a decisive factor in the outcome of the procedure. Nel (1989) carried out quantitative research to determine the effect of a pre-operative education programme on CABG patients. This education programme is based on the fact that a person's emotional disposition is a critical variable in his successful recovery from coronary disease. However, the researcher is of the opinion that although Nel's study made a positive contribution regarding this phenomenon, a quantitative research design does not reflect the real experience of the patients that follow a pre-operative education programme. In the researcher's view, a qualitative research design is more appropriate. The aim of the present qualitative, exploring, descriptive, contextual research is to explore and describe the experience of CABG patients exposed to a pre-operative education programme and to lay down guidelines for nursing staff in practice The research was conducted in three phases. One private hospital in Pretoria was use for the research.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13050号 / 論医博第2116号 / 新制||医||1017(附属図書館) / 33140 / (主査)教授 柳田 素子, 教授 長船 健二, 教授 福原 俊一 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Yes / Coronary artery bypass graft (CABG) using autologous saphenous vein continues to be a gold standard procedure to restore the supply of oxygen-rich blood to the heart muscles in coronary artery disease (CAD) patients with or without type 2 diabetes mellitus (T2DM). However, CAD patients with T2DM are at higher risk of graft failure. While failure rates have been reduced through improvements in procedure-related factors, much less is known about the molecular and cellular mechanisms by which T2DM initiates vein graft failure. This review gives novel insights into these cellular and molecular mechanisms and identifies potential therapeutic targets for development of new medicines to improve vein graft patency. One important cellular process that has been implicated in the pathogenesis of T2DM is protein O-GlcNAcylation, a dynamic, reversible post-translational modification of serine and threonine residues on target proteins that is controlled by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Protein O-GlcNAcylation impacts a range of cellular processes, including trafficking, metabolism, inflammation and cytoskeletal organisation. Altered O-GlcNAcylation homeostasis have, therefore, been linked to a range of human pathologies with a metabolic component, including T2DM. We propose that protein O-GlcNAcylation alters vascular smooth muscle and endothelial cell function through modification of specific protein targets which contribute to the vascular re-modelling responsible for saphenous vein graft failure in T2DM.

The objectives of this thesis are: a) To examine racial/ethnic differences in coronary artery calcification (CAC) and CAD, between symptomatic South Asians and Caucasians, matched for age, gender and conventional cardiovascular risk factors, b) To assess, using a meta-analysis model, the natural history of and stability of measurements of coronary artery calcium scoring (CACs) based on data collected from two large published trials: St Francis and EBEAT, c) To investigate the prevalence of coronary artery calcification in individuals with CT evidence for AVC, mitral valve calcification (MAC) or of both of them (AVC+MAC), d) To assess any potential association between premature CAD (<55 years in first-degree male relatives and <65 years in first-degree female relatives) and CAC in a large cohort of asymptomatic individuals. We found that coronary artery calcification is more extensive and diffuse in symptomatic patients of South Asian ethnic origin as compared to Caucasians, despite similar conventional risk factors for CAD. This is more evident in those >50 years of age, suggesting potential genetic or other risk factors yet to be determined. The natural history of coronary artery calcification was overtime progression in the majority of subjects, irrespective of gender. The higher variability in RCA measurements could be related to the low baseline CACs or exaggerated movement of the right side atrioventricular ring, whereas those for LCA brances are influenced by the branch allocation of the CACs. Valve calcification is not isolated but involve also and the coronary arteries. The presence of calcification in the aortic valve or combined aortic and mitral valves predicted coronary artery calcification. Additionally patients in whom both valves have become calcified tend to have severe coronary artery calcification. And finally, there is no relationship between the prevalence and extent of coronary artery calcification and the presence of family history of coronary heart disease in asymptomatic individuals with none of the conventional risk factors for atherosclerosis.

The anomalous origin of coronary arteries has been extensively documented in the literature. Most of the anomalies are incidentally found either during coronary angiography or imaging studies and are usually benign; however, malignant outcomes have been reported in the literature. Here, we present the case of a 76-year-old male with non-ST segment elevation myocardial infarction who was found to have an asymptomatic anomalous origin left anterior descending artery from the right sinus of Valsalva.

Submitted in partial fulfilment of the requirements for the Degree of Masters in Technology: Clinical Technology, Durban University of Technology, 2009. / Currently, off-pump coronary artery bypass surgery (OPCAB) is a selectively employed technique for myocardial revascularization used in the majority of heart units worldwide. This strategy obviates the documented deleterious effects of cardiopulmonary bypass. However the occurrence of neurological sequelae associated with OPCAB ranges from minor cognitive dysfunction to major stroke. Haemodynamic instability throughout the positioning, stabilization and interruption of coronary blood flow are regarded as important factors that affect the performance of off-pump surgery. Fluctuations during the perioperative period, in particular manipulation of the heart could result in temporary brain hypoperfusion and neurological sequelae. To predict those patients that are predisposed to cerebral complications, investigators have used neurological monitoring, in particular Near-infra red spectroscopy (NIRS) during cardiac surgery. Aims and Objectives of the study This prospective, observational study was carried out to assess the correlation between cerebral oxygen saturation and central venous saturation during OPCAB surgery. Central venous saturation is an important variable used to assess global tissue perfusion and could therefore be advocated as a surrogate measure of cerebral oxygen saturation. In addition variables such as mean arterial (MAP) pressure, heart rate (HR), patient oxygen saturation (SpO2), partial pressure of carbon dioxide (PcvCO2), haematocrit (Hct) and lactate were also measured to determine if they were independent predictors of cerebral desaturation. This study is one of the first done in the South African population group. iv Methodology Twenty patients undergoing OPCAB surgery from the Cardiothoracic unit at Inkosi Albert Luthuli Central Hospital, Durban, South Africa were recruited in the trial. Cerebral somasensors were placed on the patients forehead to measure left and right cerebral saturations. These sensors were linked by cables to the cerebral monitor (NIRS), INVOS model 5100C. Eight time periods throughout the surgical procedure whereby patients would be haemodynamically unstable were identified. These time periods included, post induction and pre sternotomy, pre and post placement of swabs beneath the heart, pre and post placement of the stabilizer device (Octopus), pre and post snaring of the LAD (left anterior branch of the coronary arteries), pre anastomosis and during anastomosis of the coronary arteries, second sample during anastomosis and post anastomosis, pre and post removal of swabs from beneath the heart, pre and post transfer of the patient to the ICU bed. These time periods constituted the sampling period pre and post manoeuvres. Eight paired measurements, i.e., MAP, PaCO2, HR, Hct, lactate, SpO2, central venous saturation (ScvO2) and cerebral oxygen saturation (rSo2) per patient were taken during these time periods. Recording of cerebral saturations and blood samples from the central venous line were taken during these eight time periods in order to determine the correlation between central venous and cerebral oxygen saturations. Results Strong positive correlations between central venous saturation and cerebral saturation presented in majority of the sampling time periods throughout the study (post induction and pre sternotomy, post placement of swabs beneath the heart, post snaring of the LAD (left anterior branch of the coronary arteries, pre anastomosis and during anastomosis of the coronary arteries, second sample during v anastomosis, pre and post transfer of the patient to the ICU bed). The positive correlation indicates that central venous saturation can be used as a surrogate measure of cerebral oxygen saturation during OPCAB surgery. Conclusion The absence or poor correlation of MAP, HR, PcvCO2, heamatocrit, lactate, and patient saturation to cerebral saturation in this study suggests that insertion of a central venous line (CVP) during OPCAB should be a fundamental clinical requirement.

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.

Depression is highly prevalent in coronary artery disease (CAD) and confers an increased risk of morbidity and mortality, yet mechanisms are unknown. Platelet activating factor (PAF) lipids are associated not only with CAD but also with inflammation, oxidative/nitrosative stress, vascular endothelial dysfunction and platelet reactivity which are proposed etiopathological mechanisms for depression. This study investigated the relationship between PAF species and depressive symptoms in 20 CAD patients. Plasma analyses were performed using electrospray ionization mass spectrometry (precursor ion scan). Primary analysis revealed no association between the potent pro-inflammatory PAF PC(O-16:0/2:0) and depressive symptoms measured by the Hamilton Depression Rating Scale [HAM-D] (F=0.405, p=0.533) or Beck Depression Inventory [BDI]-II (F=0.120, p=0.733) in a linear regression. Exploratory analyses revealed potential associations between greater PC(O-18:1/0:0) and greater HAM-D score and greater PC(O-22:6/2:0) concentrations with a greater BDI-II score. This study suggests that specific PAFs might be biomarkers for depressive symptoms in CAD patients.

Depression is highly prevalent in coronary artery disease (CAD) and confers an increased risk of morbidity and mortality, yet mechanisms are unknown. Platelet activating factor (PAF) lipids are associated not only with CAD but also with inflammation, oxidative/nitrosative stress, vascular endothelial dysfunction and platelet reactivity which are proposed etiopathological mechanisms for depression. This study investigated the relationship between PAF species and depressive symptoms in 20 CAD patients. Plasma analyses were performed using electrospray ionization mass spectrometry (precursor ion scan). Primary analysis revealed no association between the potent pro-inflammatory PAF PC(O-16:0/2:0) and depressive symptoms measured by the Hamilton Depression Rating Scale [HAM-D] (F=0.405, p=0.533) or Beck Depression Inventory [BDI]-II (F=0.120, p=0.733) in a linear regression. Exploratory analyses revealed potential associations between greater PC(O-18:1/0:0) and greater HAM-D score and greater PC(O-22:6/2:0) concentrations with a greater BDI-II score. This study suggests that specific PAFs might be biomarkers for depressive symptoms in CAD patients.