Orientadores: Jose Ranali, Darceny Zanetta Barbosa / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-04T04:03:18Z (GMT). No. of bitstreams: 1 Oliveira_PatriciaCristinede_D.pdf: 14172731 bytes, checksum: a824d5516bc922567d636ef268423166 (MD5) Previous issue date: 2005 / Resumo: Este estudo avaliou a variação de parâmetros cardiovasculares em 15 portadores de DAC aguda com angina instável e infarto agudo do miocárdio prévio, submetidos a tratamento odontológico sob anestesia local com epinefrina e felipressina. MAPA e ECG foram usados para avaliar a pressão arterial sistólica (PAS), pressão arterial diastólica (PAD), freqüência cardíaca (FC), extrassístoles ventriculares (EV) e supraventriculares (ESV), depressão e elevação do segmento SI. Adicionalmente foram avaliados a alteração na troponina I (Tn-I), a saturação de oxigênio (Sp02) com oxímetro de pulso, o grau de ansiedade (através da Escala de Ansiedade Dental de Corah - EADC) e a sensação dolorosa (pela Escala de dor de 11 pontos em caixa - EC), em quatro fases: 0- basal, monitoramento com holter por 24 horas; 1 ¿ simulação do atendimento odontológico, holter por 24 horas, MAPA por 5 horas, oxímetro de pulso por 1 hora que corresponde ao período do atendimento odontológico; 2 e 3 - similar à fase 1 porém com atendimento odontológico que constituiu de anestesia local infiltrativa vestibular e submucosa palatina com 1,8mL de lidocaína 2% com adrenalina 1:100.000 ou de prilocaína 3% com felipressina 0,03Ul/mL seguida de raspagem periodontal. As soluções anestésicas foram distribuídas de forma aleatória em cada uma das fases, em um estudo cruzado, cego para o atendimento e duplo-cego para a análise dos dados. As fases 2 e 3 foram acompanhadas por um cardiologista no período correspondente ao do atendimento odontológico. Antes do início das sessões, aplicou-se a EADC e, após o atendimento odontológico (fases 2 e 3), aplicou-se a EC. Os dados de ansiedade, dor, PAS, PAD e FC foram avaliados pelo teste de Wilcoxon pareado com nível de significância de 5%, ou com fator de correção de Bonferroni para os casos de três (a= 0,016) ou quatro (a= 0,0125) testes, e as variáveis do ECG pelo teste exato de Fisher (u= 0,05). A PAS apresentou diferença significante durante o atendimento odontológico com epinefrina e a Sp02 foi diferente com tendência de apresentar menor valor na fases inicial do estudo (Fase 1). Não foram encontradas diferenças significantes entre as fases para EV, ESV, depressão de ST, Tn-I, ansiedade e dor. Pode-se concluir que a epinefrina e a felipressina tiveram tendência de alterar a PAS, PAD e Sp02 embora somente a epinefrina tenha influenciado de forma significante. Porém este aumento não foi suficiente para induzir alterações eletrocardiográficas no grupo de pacientes avaliados, podendo-se dizer que ambas as soluções, na dose e concentração utilizadas, são bem toleradas por portadores de DAC aguda o tipo AI e IAM prévio, não contra-indicando, portanto o atendimento - deste grupo de pacientes / Abstract: The purpose of this study was to evaluate the changes of cardiovascular parameters in 15 volunteers with acute CAD (instable angina and previous myocardial infarction) during dental treatment under local anesthesia with epinephrine and felypressine. Ambulatory monitoring (BPAM) and ECG were utilized to evaluate systolic (SBP) and diastolic (OBP) blood pressures, heart rate (HR), ventricular (VA) and supraventricular arrhythmias (SVA), ST depression and ST elevation, and SpO2(by pulse oximeter), troponin I (Tn-I), anxiety (by Corah's Dental Anxiety Scale - CDAE) and painful sensibility (by The 11-point Box Scale - BS-11), in 4 phases: 0- baseline, 24 hours holter monitoring; 1 - dental treatment simulation, 24 hours holter, 5 hours MAPA, 1 hour pulse oximeter, corresponding the dental treatment; 2 and 3 - similar to phase 1, more dental treatment with periodontal scaling, made under maxillary and palatine local anesthesia using 1.8ml of 2% lidocaine with 1:100.000 epinephrine (Epi) or 3% prilocaine supplemented 0,03 IUlml of felypressine (Fel), in a double blind cross-over study. Phases 2 and 3 were looked closely by a cardiologist. The COAE was applied at the beginning of the sections and after the dental treatment (phases 2 and 3) was applied the BS-11. The anxiety date, painful sensibility, SBP, DBP and HR were evaluated by Wilcoxon test (5% levei of significance or Bonferroni correction factor for the cases of three, u= 0.016 or four, u= 0.0125 tests) and the data of ECG were analyzed by Fisher test (u= 0.05). The SBP presented significant difference during dental treatment with epinephrine and SpO2was different with tendency to showed lowers values in phase 1. Significant differences were not found among the phases for VA, SVA, ST depression, Tn-I, anxiety and painful sensation. It can be concluded that epinephrine and felypressine resulted changes in SBP, OBP and SpO2, but only' epinephrine caused significant difference. However the SBP did not increased sufficiently to cause ECG alterations in this group, and both of them, in utilized doses and concentrations are well tolerated by patients with acute CAD (instable angina and myocardial infarction), it did not presented absolute contraindications to dental treatment in this grou / Doutorado / Farmacologia, Anestesiologia e Terapeutica / Doutor em Odontologia

Abstract Interest in off-pump coronary surgery and ischaemic preconditioning has been increasing. The aim of this study was to evaluate surrogate indicators of haemodynamic, myocardial, and cerebral outcome during off-pump surgery and preconditioning. Haemodynamics and myocardial preservation were monitored in a pilot study of twelve patients undergoing off-pump coronary surgery. Indicators of myocardial metabolism and tissue injury as well as cerebral damage were evaluated in a randomized study of thirty-three patients undergoing on-pump (11) or off-pump surgery with (11) or without (11) preceding myocardial ischaemic preconditioning for five minutes followed by reperfusion for five minutes. The pilot study showed minimal haemodynamic changes and myocardial derangements during off-pump surgery as evaluated intraoperatively based on transcardiac differences of ATP degradation products and lactate and postoperatively based on MB mass of creatine kinase and troponin T. In the following studies, myocardial ischaemic metabolism was evaluated intraoperatively by measuring transcardiac differences of ATP degradation products, lactate, and pH, which increased significantly from the baseline values in all study groups. However, the maximum values of lactate and pH were significantly higher in the cardiopulmonary bypass group (p = 0.02 and p = 0.007, respectively). There were no statistical differences between the preconditioning and non-preconditioning groups. Myocardial tissue injury was evaluated by postoperative leakage of MB mass of creatine kinase and troponin I. Their peak values were significantly higher (p < 0.001 and p = 0.008) after cardiopulmonary bypass (15.1 μg/l and 13.8 μg/l) than after off-pump surgery without preconditioning (6.3 μg/l and 5.2 μg/l). The respective values were 14.8 μg/l and 7.4 μg/l after preconditioning, and there were no statistically significant differences between the off-pump groups with and without preconditioning. Cerebral damage was evaluated based on the intra- and postoperative serum concentrations of neuron-specific enolase, which were corrected with respect to haemolysis. The corrected values were significantly higher after on-pump than off-pump surgery (p = 0.003 and p = 0.005). In conclusion, multi-vessel off-pump coronary artery surgery is a haemodynamically feasible procedure offering better myocardial preservation compared to on-pump surgery. Ischaemic preconditioning of the myocardium does not seem to improve myocardial preservation in off-pump surgery. The slightly lower levels of neuron-specific enolase also suggest less cerebral damage.

Abstract The purpose of this prospective, clinical longitudinal survey was to describe, explain and understand the subjective quality of life and life course of patients with coronary artery disease. The study subjects' quality of life was assessed at the time of the onset of coronary artery disease, during the treatment process and during rehabilitation. Altogether 280 patients participated, of whom 80 were treated with medication, 100 with transluminal angioplasty, and 100 with bypass surgery. The study population consisted of 189 men and 91 women. At the baseline, the study subjects' self-care agency was measured with the Self-As-Carer Inventory (SCI). The subjects health-related quality of life was assessed with the Nottingham Health Profile (NHP) at the baseline as well as at 6 and 12 months after the procedure. The qualify of life of coronary artery disease patients was compared to the quality of life of an age- and sex-matched Finnish adult population (N = 3600) by using a previous standardisation of the NHP instrument. One year after the treatment, 19 patients who had undergone either bypass surgery or angioplasty attended thematic interviews at their homes. Triangulation of methodologies, methods and data collection was used in the study. The qualitative analysis of personal experiences was carried out using the method of phenomenological psychology described by Amedeo Giorgi based on Husserl's descriptive phenomenology. Before the treatment procedures, the quality of life of the coronary artery disease patients was significantly poorer than that of the age-matched adult population on the dimensions of energy, pain, emotional reactions, sleep and mobility. Moreover, the female patients with coronary artery disease had poorer health-related quality of life than the corresponding male patients, especially on the dimensions of energy, sleep, emotional reactions and mobility. The quality of life of the patients who had undergone angioplasty or bypass surgery was statistically significantly better one year after surgery on the dimensions of energy, pain and mobility. Their quality of life had, however, deteriorated on the dimensions of emotional reactions and social isolation. The thematic interviews revealed two kinds of life course: one with an active attitude towards treatment and a re-orientation of life course and another with a passive attitude towards treatment and a maintenance of the old principles in one's life course. A need for rehabilitation was indicated by an onset of the illness suddenly at a relatively young age, termination of an active working career, financial problems, dissatisfaction with the outcome of treatment, problems in family relations, and a desolate view of the future. An increased need for psychosocial support was especially common among women, subjects with recurrence and both male and female subjects in the youngest age group. According to the subjects, after-care failed to meet their needs or to address their problems. No continuous and confidential therapeutic relationships emerged. The problems included inadequate knowledge of one's condition and a lack of detailed instructions concerning the permissible degree of exertion after treatment. The patients felt they needed rehabilitation groups with coronary artery disease patients similar to themselves. The study yielded new knowledge about the health-related quality of life of coronary artery disease patients, the connections between the treatment methods and the changes in the patients' quality of life during one year and the patients' experiences at the time of the diagnosis and during the periods of treatment and after-care. This evidence-based knowledge can be used to develop the treatment and rehabilitation of coronary artery disease patients and to plan further research.

Philosophiae Doctor - PhD / Background: There is compelling body of evidence that coronary heart disease (CHD) risk factors are present in people of all ages. The extent to which the problem exists in university students in South Africa (SA) has not been confirmed in the literature. Furthermore, the effects of physical activity, physical fitness, diet and health behaviours on CHD risk factors has not been studied extensively in SA and needs further investigation. Aim: The aim of the study was to assess the impact of multiple behaviour health intervention strategies on CHD risk, health-related physical fitness(HRPF) and healthrisk behaviours (HRB) in first year students at the University of the Western Cape (UWC). It was hypothesized that exposure to various health behavioural interventions would reduce CHD risk factors in subjects at moderate risk, and improve health-related physical fitness, as well as health-risk behaviours.Methods and Study Design: An experimental study design was used wherein subjects at moderate risk for CHD were identified and exposed to multiple health behavioural interventions for 16 weeks in order to determine the impact of the various interventions on CHD risk, health-related physical fitness and health-risk behaviours. Population and Sample: The target population consisted of first year students at UWC aged 18 – 44 years who were screened and a sample of 173 subjects were identified as being at moderate risk for CHD. Next, the subjects were randomly assigned to a control and four treatment groups, namely, health information, diet, exercise, and a multiple group that included all three treatments. The intervention, based upon Prochaska‟s Transtheoretical Model of behaviour change, continued for a period of 16 weeks and, thereafter, the subjects were retested. Data Collection Process: Subject information was obtained using self-reported questionnaires, namely, the physical activity readiness questionnaire (PAR-Q), the stages of readiness to change questionnaire (SRCQ), the international physical activity questionnaire (IPAQ), and the healthy lifestyle questionnaire (HLQ), together with physical and hematological (blood) measurements. The measurements taken before and after the intervention programme were the following:• Coronary heart disease risk factors, namely: family history, cigarette smoking, hypertension, obesity, dyslipidemia, impaired fasting glucose and a sedentary lifestyle; • Health-related physical fitness, namely: body composition, cardiovascular fitness, muscular strength, muscular endurance, and flexibility; and • Health-risk behaviours, namely: physical activity, nutrition, managing stress, avoiding destructive habits, practising safe sex, adopting safety habits, knowing firstaid, personal health habits, using medical advice, being an informed consumer, protecting the environment and mental well-being. Types of interventions: A control group was used in which subjects did not receive any treatment. The health behavioural interventions were arranged into four groups of subjects that received either the health information, diet, exercise or a combination of all three individual treatments. Statistical analyses of data: In the analyses of the data, the procedure followed was that where the outcome variable was approximately normally distributed, the groups were compared using a two-sample t-test. For outcomes with a highly non-normal distribution or ordinal level data, the nonparametric Wilcoxon Rank Sum test was used for group comparisons. To account for baseline differences, repeated measures analysis of variance was used. In the case where nonparametric methods were appropriate, analysis was done using Cochran-Mantel-Haenszel (CMH) methodology stratifying on the baseline values. For the case of nominal level outcomes, groups were compared by Chi-square tests for homogeneity of proportions. When baseline values needed to be incorporated into the analysis, this was done using CMH methodology. Main Outcome Measures: The main outcome measures tested in the study related to the three areas of investigation, namely: • Modifiable CHD risk factors: systolic and diastolic blood pressure, cigarette smoking, total cholesterol (TC) concentration, high-density lipoprotein (HDL) cholesterol concentration, low-density lipoprotein (LDL) cholesterol concentration, triglycerides, fasting glucose, body mass index, waist circumference, waist-hip ratio and physical inactivity; • Health-related physical fitness: body mass, percent body fat, absolute body fat, percent lean body mass, absolute lean body mass, the multi-stage shuttle run, handgrip strength, repeated sit-ups in a minute, and the sit-and-reach test; and • Health-risk behaviours: physical activity, nutrition, managing stress, avoiding destructive habits, practising safe sex, adopting safety habits, knowing first aid, personal health habits, using medical advice, being an informed consumer, protecting the environment and mental well-being. Results: The results showed significant decreases for body mass, waist and hip circumferences, resting heart rate, systolic blood pressure, cigarette smoking and a sedentary lifestyle (p < .05) primarily in the multiple group. No significant differences were recorded for blood biochemistry, however, favourable trends were observed in the lipoprotein ratios. For health-related physical fitness, only the multiple group showed significant (p < .005) improvements in predicted maximal oxygen consumption ( O2max), body composition, muscular strength and muscular endurance. The exercise group also recorded significant differences in muscular endurance. In all groups, including the controls, no significant differences were found for stature, waist-hip ratio, and flexibility at pre- and post-test. Overall, the participants reflected positive health behaviours, especially for managing stress, avoiding destructive habits, practising safe sex, adopting safety habits, personal health habits and mental well-being at pre- and post-test. The intervention programme had a corrective influence on providing the participants with a more realistic perception of their level of physical activity and nutritional habits. The participants scored poorly on being informed consumers and for recycling waste both at pre- and post-test. A substantial net reduction in CHD risk factors as well as in cumulative risk was achieved with treatment that impacted positively on the re-stratification of participants at moderate risk. In terms of treatment efficacy, the dietary intervention appeared to be the least effective (10.91%), with health information and exercise sharing similar levels of efficacy (32.81% and 33.93%, respectively) and, the combined treatment in the multiple group stood out as the most effective treatment (50.00%), and supported the hypothesis of the study. Conclusions: The net and cumulative decline in CHD risk factors was substantial with treatment and was directly related to the number of treatments administered. The evidence suggests that such multiple health behaviour interventions when implemented through a university-based setting have substantial benefits on reducing CHD risk and may be of considerable public health benefit. Key messages • Despite being a relatively educated population, a substantial number of first year university students are at considerable heart disease risk. • Physical inactivity constitutes one of the main CHD risk factors amongst first year students and, together with smoking, place many of them at moderate CHD risk. • The effectiveness of health behavioural strategies designed to modify lifestyle and prevent coronary heart disease is supported by this study.

Introduction: Atherosclerosis remains asymptomatic until it progresses to cause flow-limiting disease. Identifying patients at high risk in the early stages of the atherosclerotic process may allow modification of cardiovascular risk by effective preventive strategies. Various non-invasive tests have been studied and have shown promising results in predicting future adverse cardiovascular events. The objective of this study was to establish the carotid ultrasonographic markers that best correlate with angiographic coronary artery disease (CAD) and the relationship between left ventricular geometry, carotid atherosclerosis, biomarkers and CAD in patients with unobstructed coronary arteries, chronic stable angina (CSA) and acute coronary syndromes (ACS). Methods: Carotid ultrasound examination, echocardiography and serum biomarker estimation were performed in consecutive patients who underwent coronary angiography for evaluation of stable or acute chest pain. Results: A total of 146 subjects were recruited into the study with a mean age of 56.9 ± 10.6 (range 29 to 85) years; 120 were men (82%) and 26 (18%) women. Twenty-one percent of the study population had unobstruced coronaries, 42% had stable CAD and 37% had presented with ACS. There was no significant difference in the carotid intima media thickness (CIMT) measurements between the three groups. CIMT correlated with abnormal left ventricular geometry but not with the presence or severity of CAD. The presence of carotid plaque and plaque score correlated with obstructive CAD, but was not significantly different between stable CAD and ACS patients. There was a trend towards more echogenic plaque in the stable CAD group. The composite score of IMT and plaque was positively correlated with the presence and severity of CAD. The averaged myocardial peak systolic and early diastolic velocities were significantly lower in those with obstructive CAD. CRP and osteopontin levels were higher in the ACS patients. Conclusions: Carotid plaque and not CIMT was associated with angiographic coronary artery disease. Averaged systolic and early diastolic myocardial velocities by tissue doppler imaging correlated with obstructive CAD. Novel serum biomarkers are promising and further studies are needed.

Angiogenic cell therapy is currently being developed as a treatment for coronary artery disease (CAD); however, endothelial dysfunction (ED), commonly found in patients with CAD, impairs the ability for revascularization to occur. We hypothesized that culture on a collagen matrix will improve survival and function of circulating progenitor cells (CPCs) isolated from a mouse model of ED. Overall, ED decreased the expression of endothelial markers in CPCs and impaired their function, compared to normal mice. Culture of CPCs from ED mice on collagen was able to increase cell marker expression, and improve migration and adhesion potential, compared to CPCs on fibronectin. Nitric oxide production was reduced for CPCs on collagen for the ED group; however, CPCs on collagen had better viability under conditions of serum deprivation and hypoxia, compared to fibronectin. This study suggests that a collagen matrix may improve the function of therapeutic CPCs that have been exposed to ED.

Increasingly, cell-based therapy with autologous progenitor populations, such as endothelial progenitor cells (EPC), are being utilized for treatment of vascular diseases. However, both the number and functional capacity are diminished when cells are derived from patients with established risk factors for coronary artery disease (CAD). Herein, we report that inhibition of glycogen synthase kinase 3 (GSK) can improve both the number and function of endothelial progenitor cells in patients with CAD or diabetes mellitus (DM) leading to greater therapeutic benefit. Specifically, use of various small molecule inhibitors of GSK (GSKi) results in a 4-fold increased number of EPCs. Moreover, GSKi treatment improves the functional profile of EPCs through reductions in apoptosis, improvements in cell adhesion through up-regulation of very-late antigen-4 (VLA-4), and by increasing paracrine efficacy by increasing vascular endothelial growth factor (VEGF)secretion. Therapeutic improvement was confirmed in vivo by increased reendothelialization(RE) and reductions of neointima (NI) formation achieved when GSKi-treated cells were administered following vascular injury to CD-1 nude mice. Because cell-based therapy is technically challenging, we also tested a strategy of local delivery of GSKi at the site of arterial injury through GSKi-eluting stents. In vitro, GSKi elution increased EPC attachment to stent struts. In vivo, GSKi-eluting stents deployed in rabbit carotid arteries resulted in systemic mobilization of EPCs, improved local RE, and important reductions in in-stent NI formation. Finally, we tested the ability of GSKi to improve EPC-mediated arterial repair in patients with DM. As in patients with CAD, GSKi treatment improved EPC yield and diminished in vitro apoptosis. Utilizing a proteomics approach, we identified Cathepsin B (catB) as a differentially regulated protein necessary for reductions in apoptosis. Indeed, antagonism of catB prevented GSKi improvements in GSKi treated EPC mediated arterial repair in a xenotransplant wire injury model. Thus, our data demonstrates that GSKi treatment results in improvements in EPC number and function in vitro and in vivo resulting in enhanced arterial repair following mechanical injury. Accordingly, GSK antagonism is an effective cell enhancement strategy for autologous cell-based therapy with EPCs from high risk patients such as CAD or DM.

Introdução. A elevação dos marcadores inflamatórios e de necrose miocárdica, após intervenção coronária percutânea, pode interferir nos resultados clínicos. No entanto, pouco se conhece sobre a terapia com estatinas pré-procedimento na redução destes marcadores em pacientes estáveis de baixo risco. Objetivo. Avaliar se o uso de estatina, antes do implante eletivo de stent coronário (ISC), reduz os níveis plasmáticos de marcadores inflamatórios e de necrose miocárdica, em pacientes com doença arterial coronária (DAC), estáveis e de baixo risco. Métodos. Neste estudo observacional prospectivo, 100 pacientes (n=50 em uso de estatina vs n=50 sem uso de estatina) com DAC estável foram submetidos à implante eletivo de stent coronário. Marcadores inflamatórios (proteína C reativa [PCR], interleucina[IL] -6, fator de necrose tumoral- e matrix metaloproteinase-9) e marcadores de necrose miocárdica (troponina I e CK-MB ) foram dosados antes e 24 horas após o implante eletivo de stent coronário. Resultados. Todos os pacientes apresentaram um aumento significativo de PCR e IL-6, após ISC. No entanto, esse aumento foi anulado em pacientes que faziam uso de estatina antes de ISC em relação àqueles que não tomavam estatina: 75% vs 150% (p <0,001) e 192% vs 300% (p <0,01) respectivamente. Os outros marcadores pró-inflamatórios foram semelhantes para os dois grupos de pacientes. Troponina I e CK-MB não se alterou, após ISC, independentemente, da terapia com estatina anterior ou não. Conclusão. O pré-tratamento com estatina reduz a magnitude da inflamação após ISC, demonstrada por aumentos significativamente menores de PCR e IL-6, em pacientes com DAC, estável e de baixo risco. Lesão miocárdica periprocedimento foi irrelevante e não foi afetada pela terapia com estatina pré-procedimento nesta população / Background. The elevation of markers of inflammatory and myocardial necrosis after percutaneous coronary intervention may interfere on clinical outcome. However, little is known concerning preprocedural statin therapy on the reduction of these markers in stable patients at low-risk. Objective. To evaluate if statin therapy prior to elective coronary stent implantation (CSI) reduces the plasma levels of markers inflammatory and myocardial necrosis in patients with low-risk stable coronary artery disease (CAD). Methods. In this prospective, observational study, 100 patients (n=50 on statin therapy vs n=50 not on statin) with stable CAD underwent elective CSI. Inflammatory (C-reactive protein [CRP], interleukin [IL]-6, tumor necrosis factor-a and matrix metalloproteinase-9) and myocardial necrosis markers (troponin I and CK-MB) were determined before and 24 hours after CSI. Results. All patients presented a significant increase of CRP and IL-6 after CSI. However, this increase was blunted in patients on statin therapy prior to CSI than those without statin therapy: 75% vs 150% (p<0.001), and 192% vs 300% (p<0.01), respectively for PCR and IL-6. The other pro-inflammatory markers were not affected in both sets of patients. Troponin I and CK-MB did not change after CSI regardless of previous statin therapy or not. Conclusions. Previous treatment with statins reduces the magnitude of procedural inflammation, denoted by markedly lower increases of CRP and IL-6 levels, in elective CSI on stable CAD patients. Periprocedural myocardial injury was not significant in this population

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23057号 / 医博第4684号 / 新制||医||1048(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 森田 智視, 教授 湊谷 謙司, 教授 川上 浩司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Background: Glycation influences the ultrastructure and clot kinetics of fibrin clots due to the post-translational modifications in fibrinogen. Methylglyoxal (MG) is used to measure the level of glycation which has been associated with the pathogenesis of type 2 diabetes Melilites (T2DM) and coronary heart disease (CHD). The aim of the study was to determine the role of MG on clot kinetics and fibrin clot structure in CHD patients with and without T2DM to provide insight into the mechanism of pathogenesis of atherosclerosis in T2DM which results in the development of CHD. Methodology: Scanning electron microscopy (SEM) was used to evaluate the morphology of fibrin clots. Thromboelastography (TEG) was used to assess the physiological clot properties (kinetics). Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of methylglyoxal-adducts. Results: The morphology of clots from controls analysed using SEM showed thick and thin fibres which created an organised mesh of fibrin fibres. In T2DM, CHD with T2DM and CHD some alterations in the morphology were observed. The ultrastructure micrographs in CHD shows that some of the fibrin fibres formed have individual fibres with both thick and thin fibres as well as a thick mass of fibres with a net-like structure that forms dense-matted deposits. In addition, the fibrin fibres are not organised. The densitometry analysis between controls and patient groups’ (CHD: mean (standard deviation) 0.42±0.11; CHD+T2DM: 0.31±0.08 and T2DM: 0.29±0.08) was found to be significantly lower in all groups compared to the control which had a mean of 0.57±0.1, p<0.0001. There are no significant differences in the alpha angle between CHD, T2DM, CHD with T2DM and controls (60.88±2.321˚ vs. 60.81±2.385˚ vs. 59.09± 3.185˚ vs. 66.47±1.300˚, p=0.5279). There was no significant difference found in the K-value between T2DM, CHD with T2DM, CHD and control subjects (3.458±0.446mins vs. 5.118±1.589mins vs. 3.758±0.450mins vs. 2.839±0.2156mins, p=0.0102). The maximum amplitude was higher in T2DM patients compared to CHD, CHD with T2DM and controls (40.51±1.914mm vs. 34.10±2.127mm vs. 33.12±3.365mm vs. 33.60±1.525mm, p=0.0102). The MRTG was higher in CHD compared to T2DM, CHD 4 with T2DM and controls (10.74±3.335 dyn cm-2 s -1 vs. 4.268±0.690 dyn cm-2 s -1 vs. 5.046± 0.927 dyn cm-2 s -1 vs. 6.535±0.664 dyn cm-2 s -1 , p=0.0096). The reaction time was higher in CHD with T2DM patients compared to T2DM, CHD and controls (32.58±4.005min vs. 23.92±2.793min vs. 21.29± 2.383min vs. 8.322±0.886min, p<0.0001). There was no significant difference found in the TTG between T2DM, CHD with T2DM, CHD and control subjects (231.3±28.68 dyn cm-2 vs. 258.5±38.15 dyn cm2 vs. 343.7±71.92 dyn cm-2 vs. 287.7±21.37 dyn cm-2 , p=0.8421). The TMRTG was higher in T2DM patients compared to T2DM, CHD with T2DM, CHD and controls (23.91±2.409mins vs. 20.46±3.411mins vs. 14.14±1.287mins vs. 10.16±0.751mins, p<0.0001). To assess if an association between MG-adducts and clot kinetics exists, the Spearman r correlation was completed for each clot parameter. The reaction time (p=0.0047, 95% CI: 0.138 to 0.665) and time taken before maximum speed of the clot growth to be achieved (p=0.3958, 95% CI: 0.072 to 0.644) was significant. This indicates the relationship between the parameters i.e., the higher the level of MGadducts present, the longer it takes for clotting to begin and reach maximum speed of formation. Conclusion: This study showed that there are ultrastructural differences in fibrin fibres formed in CHD patients with T2DM. The viscoelastic parameters indicated that haemostasis was irregular in CHD and T2DM. The levels of MG-adducts were much higher in T2DM, CHD with T2DM and CHD and may be a contributing factor to the pathogenesis associated with altered coagulation in these patients. / Dissertation (MSc (Physiology))--University of Pretoria, 2020. / NRF / Physiology / MSc (Physiology) / Unrestricted