Thesis (Ph. D.)--University of Washington, 1989. / Vita. Includes bibliographical references (leaves [94]-105.).

It is widely accepted that the occurrence of myocardial infarction (MI) among Black South Africans is much lower than that of South Africans of European or Asian ancestry. Over the past decade, this disease among Black Africans in urban areas appears tc be increasing. The prevalence of MI among Black Africans admitted fo Baragwanath Hospital (BGH) over a four year period (1984-1987) was determined by computer identification of all patients demonstrating elevated creatine kinase isoenzymes. Diagnosis of MI was confirmed by reviewing the hospital bedletters.

Thesis (M.A.)--Boston University / Rat heart muscle was subjected to quantitated conditions of anoxia achieved by extracting oxygen from Ringer's solution under vacuum and heat. Special Van Slyke analyses measured the amount of oxygen remaining in solution after the extraction procedures had been carried out. Myocardial response to anoxia was studied in terms of survival, or the ability of the heart tissue to remain alive during anoxia with resumption of function when placed in an oxygenated environment, and in terms of function, or the ability of heart muscle to contract during anoxia [TRUNCATED]

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Science in Occupational Therapy Johannesburg / Visual perceptual impairment is a common consequence of stroke which may affect all areas of occupational performance. The evidence for the management of these deficits in occupational therapy is not clear. The purpose of this qualitative study was therefore to determine the expert opinion for best practice in the management of visual perceptual deficits in adults post stroke in the South African context. Interviews with eight expert occupational therapists indicated that a lack of clarity exists in this area of clinical practice. Findings indicate this is a complex area of practice where management needs to be focussed on occupation based therapy for the individual patient in their context. The use of standardised and non-standardised assessments and compensation verses remediation in intervention must be individually determined, and the use of a “top down” approach was considered preferable. This study presents the first step in the development of clinical guidelines for management of this deficit in occupational therapy in South Africa.

The prevention of heart failure in our aging population has become a healthcare priority. As part of the normal aging process patients have been shown to develop age-related myocardial fibrosis, which is characterized by excess deposition and a lack of clearance of extracellular matrix (ECM) proteins, contributing to the development of heart failure. The increase in ECM proteins is caused by an imbalance between the following: (1) collagen biosynthesis by fibroblasts, (2) post-synthetic collagen processing (cross-linking) which stabilizes collagen, and (3) collagen degradation. The focus of this thesis lays mainly on collagen biosynthesis and processing, and how interrupting these can affect the overall balance of collagen in the myocardium. The two main objectives of this thesis lay in 1 – characterizing the role of a key pro-fibrotic signal in the TGFβ pathway, connective tissue growth factor (CTGF), in hypertension induced myocardial fibrosis development, and 2 – investigating the role of lysyl oxidase (LOX), an enzyme involved in the crosslinking of collagen that has been implicated in age-related myocardial fibrosis development. This thesis provides novel evidence that CTGF regulation is an important step in the early stages of myocardial fibrosis development through regulating new collagen synthesis and that CTGF is produced as a downstream mediator of TGFβ after AngII exposure not directly through AngII-AT1R signaling. Additionally, novel evidence is presented that LOX inhibition reduces age-related myocardial fibrosis and that the decrease in collagen protein content observed after LOX inhibition is associated with a significant decrease in new pro-collagen 1 mRNA synthesis. This suggests that LOX inhibition also inhibits new collagen synthesis by an unknown mechanism. Overall, these studies have contributed new mechanistic knowledge about myocardial fibrosis development and explored potential therapeutic strategies aimed at interrupting collagen homeostasis, which are key to understanding myocardial fibrosis development.

Thesis (Ph. D.)--University of Louisville, 2003. / Department of Physiology and Biophysics. Vita. "December 2003." Includes bibliographical references (leaves 102-115).

The original publication is available at http://www.samj.org.za / The clinical presentation of a young hypertensive White man with acute high lateral non-transmural myocardial infarction (MI) is documented. This diagnosis was established on the grounds of a history of chest pain, elevated serial serum enzyme levels, technetium-99m pyrophosphate ('hot-spot') scintigraphy, exercise thallium-201 ('cold-spot') scanning, left ventricular cine angiography and selective coronary arteriography. Daily resting 12-lead ECGs failed to demonstrate unequivocal features of acute non-transmural subendocardial MI. The diagnostic difficulties facing the clinician in a case of acute MI associated with a non-diagnostic ECG are stressed, and the ECG features of acute subendocardial MI are reviewed. / Publishers' version

The aims of this thesis are to determine: 1. The true prevalence of hibernating myocardium in patients with severely impaired left ventricular contraction. (Chapter 3) 2. The viability status of the left ventricular wall aneurysm as defined by positron emission tomography. (Chapter 4) 3. The relationship between the incidence of hibernating myocardium and the coronary artery flow grade determined angiographically. (Chapter 5) 4. The relationship between the presence of Q waves (with or without preserved R wave) on the surface electrocardiogram and the presence of scar in the myocardium as diagnosed by positron emission tomography. (Chapter 6) 5. The relationship between the incidence of hibernating myocardium and QT dispersion on the surface electrocardiogram. (Chapter 7) 6. Looking for other markers of hibernation by PET. (Chapters 8 and 9) I proposed to look at the relationship between continuing metabolic activity in 10 akinetic or severely hypokinetic segments as an alternative method and thus as a new definition of pre-operative determination of hibernating myocardium. This is the topic in Chapter 8. Following the completion of question number 3, and the observed role of collateral circulation, I proposed to look into the role of TIMI 0-1 and collaterals grade 2-3 in maintaining viability and their role as a marker of hibernating myocardium. This won support in the form of a research grant from the British Heart Foundation in 1998. This was the topic of my last project, which was added to the thesis after its initial completion on the 23rd of December 2000. This is the topic of Chapter 9. 7. Following the delayed submission of the Thesis in 2015, I was asked to add Chapter 11 which summarised both my contribution since the Thesis was concluded into the topic of Hibernating myocardium; and the knowledge progression into the detection of the phenomenon and its clinical usefulness to bring the Thesis up to date. Methods: The patients were those with coronary artery disease and impaired left ventricular contraction recruited into a series of studies of the presence of hibernating myocardium using positron emission tomography, as the method of choice to preoperatively detect this phenomenon. The patients were either recruited from the cardiac catheterization laboratory or from the cohort of patients presenting with myocardial infarction to the cardiology unit at Aberdeen Royal Infirmary. All the studies were approved by the Grampian Research Ethics Committee. In some of the studies, cardiac magnetic resonance imaging was used for simple assessment of the myocardial contraction and thickening in the study reported in Chapter 9. Results and Conclusions: 1.   Hiberanting myocardium affects over 50% of the patients with severe left ventricular systolic impairment with coronary artery disease. (Chapter 3).   2.   None of the aneurysmal segments are viable. (Chapter 4)   3.   Compared to the areas supplied by arteries with Thrpmbolysis In Myocardial Infarction (TIMI) flow grades 2-3, the areas supplied by almost occluded coronary arteries (TIMI 0-1 flow grades) are significantly more likely to have both evidence of scarred myocardium (highly significantly statistical difference p < 0.0001) and evidence of hibernating myocardium, just reaching statistical significance (p < 0.05). (Chapter 5)   4.   The specificity of Q waves on the electrocardiogram (ECG) as markers for 11 myocardial scarring is 79%, with a low sensitivity of 41%. (Chapter 6) 5.   Maintaining R waves following a pathological Q wave on the ECG is not helpful for predicting the presence of hibernating myocardium. (Chapter 6) 6.   The presence or absence of hibernating myocardium did not impact on native QT dispersion, rate corrected QTc dispersion or on the maximum adjacent QT dispersion on the ECG. (Chapter 7). 7.   A new definition of hibernating myocardium is proposed, helping to detect it preoperatively through the demonstration of metabolism – mechanical mismatch defect using a single radio-pharmaceutical. (Chapter 8) 8.   As a marker of the classical perfusion –metabolism mismatch defect, the new proposed metabolism-mechanical mismatch defect by PET is sensitive (92%) and specific (97%), with excellent positive and negative predictive accuracies (96% and 93%, respectively). (Chapter 8) 9.   While collaterals grade 2-3 supplying territories with blocked arteries and flow grades TIMI 0-1 may be sensitive markers (83%) of hibernating myocardium; they lack specificity (20%), and the differences between the two small groups completing the study did not reach statistical significance. (Chapter 9).

ABSTRACT The Sarcolemmal Membrane Associated Protein 3 (SLMAP3) is a tail-anchored membrane protein, which is ubiquitously expressed in tissues including myocardium. It is a component of subcellular membranes and the centrosome, and it appears to serve distinct roles in cell growth and membrane biology. In addition, mutations in SLMAP have been linked to Brugada syndrome, which leads to cardiac dysfunction and death. Here, we have examined the effects of different levels of SLMAP3 on postnatal heart function, pre and post myocardial infarction (MI).Transgenic (TG) mice with a cardiac specific expression of SLMAP3 isoform were generated and assessed with echocardiography to measure function, immunohistochemistry for histology, TUNEL assay for apoptosis, Masson’s trichrome staining for fibrosis, and Western blots for protein expression. Baseline echocardiography of 8 weeks old TG mice showed a normal cardiac function that was expressed in ejection fraction percent (%EF=66%±7.42), which was similar to those of wild type mice (%EF=67%±9.36), p<0.05, n=20-25 (in each group). MI was induced by permanent ligation of left anterior descending (LAD) artery in 9 week old WT & TG mice, while sham was the control. No death was recorded in SLMAP3 TG mice up to one year post MI, whereas 70% of WT mice had deceased, p<0.01, n=17-18 (in each group). Cardiac function was assessed by echocardiography (at 4 week post MI) showed a partially restored ejection fraction percent (%EF~49.2%±17.02) in SLMAP3 TG mice post MI compared to (%EF~36.4%±15.25) in WT mice post MI, p<0.05, n=15-16 (in each group). Furthermore, infarct size (IS) as well as collagen area (CA) post MI were significantly attenuated (IS~43%±8.82, CA~35%±5.15) in SLMAP3 TG myocardium in comparison to WT (IS~53%±9.30, CA~47%±7.36), p<0.05, n=20- 22 (each group). Moreover, expression of the heart failure biomarker galectin3 was markedly ii attenuated (1.8±0.20) in SLMAP3 TG hearts post MI compared to (3.2±0.35) in WT, p<0.01, n=4-5 (in each group). The apoptotic index in SLMAP3 TG myocardium assessed by TUNEL was markedly decreased (77±11.48) in comparison to WT (112±15.32), p<0.05, (n=20-22 in each group). Further, expression of proapoptotic proteins (Caspase3 and Bax) was significantly attenuated in SLMAP3 TG (p<0.05, n=4-5 in each group) while the expression of the prosurvival proteins (Bcl2 and caveolin3) was significantly upregulated (p<0.05, n=4-5 (in each group) in post MI. These data indicate that increased SLMAP3 levels serve to protect myocardium post MI through mechanisms which promote cell survival and limit cardiac fibrosis. Strategies to increase SLMAP3 level in myocardium may provide new therapeutic options in the treatment of heart failure.

No description available.