Thesis (Ph. D.)--University of Virginia, 1992. / Includes bibliographical references (leaves 112-123). Also available online through Digital Dissertations.

Thesis - Catholic University of America. / Photocopy of typescript. Ann Arbor, Mich.: University Microfilms International, 1977. 21 cm. On spine: Patients with initial myocardial infarction. Bibliography: leaves 75-82.

Thesis--Catholic University of America. / On spine: Patients with initial myocardial infarction. Includes bibliographical references (leaves 75-82).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1970. / Vita. Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M.D.) -- University of Hong Kong, 1996. / Includes bibliographical references. Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

No description available.

Objective Increases in the number of CD34+ stem cells and progenitor cells in blood and infarcted areas after acute myocardial infarction (AMI) are a documented phenomenon. However, no study has yet reported on the dynamic changes in specific populations of adult stem cells, such as c-kit +Lin- cells or ckit + Lin - Sca1 + (KLS cells), following AMI. This study investigated the dynamic changes in these cells in multiple systems/organs following MI in mice. Methods The C57BU6J mice received either no surgery (normal control, n=6) or surgical ligation of the left anterior descending coronary artery to create AMI (n=24). On day-1 (n=7), -3 (n=5), -6 (n=6), and -12 (n=6) after AMI, mononuclear cells were isolated from theblood, spleen, and bone marrow, and stained with Lineage-PEcy7, c-kit-PE, and Sca1-APC antibodies. The c-kit +Lin - cell and KLS cell populations in the mononuclear cells were analyzed by FACS flowcytometry. Results The pattern of changes in the c-kit + Lin - cells was very similar to that in the KLS cells in the bone marrow, circulating blood, and spleen following AMI. There was a significant increase in these cells on day-3 in the bone marrow (c-kit +Lin- cells: 1.470 ± 0.094% vs control 1.127 ± 0.019%, and KLS cells: 0.365 ± 0.012 % vs control 0.1848 ± 0.019%, p<0.05), which then slowly declined from day-6 to -12. In the blood, these cells, particularly the KLS cells, decreased slightly from day-1 to -12. On day-3, -6, and -12 the cells increased continuously and significantly in the spleen, (on day 3, c-kit +Lin-cells: 0.253 ± 0.0107 % vs control 0.1305 ± 0.014 %; it was 0.3212 ± 0.028 % on day-6). (on day-6 KLS cells: 0.1078 ± 0.076 % vs control 0.0425 ± 0.0064 % while on day 12 it was 0.1174 ± 0.035 % p<0.05). Conclusion This study provides for the first time the longest observation of the dynamic changes of specific sub-groups of adult stem cells (c-kit +Lin- cells and KLS cells) in multiple systems following AMI. The study demonstrates that AMI results in significant changes, or mobilization, of these cells in the bone marrow, spleen, and blood. Significant and continuous accumulation of the cells in the spleen occurs following AMI, despite the decreased level of the cells in the blood. The role of the spleen in stem cell mobilization after AMI is unclear and requires further investigation. / Surgery, Department of / Medicine, Faculty of / Graduate

ST-segment elevation myocardial infarction (STEMI) is a common presentation of acute myocardial infarction, constituting approximately 30% of all cases. Based on the highest level of evidence for improvement in both morbidity and mortality in these patients, clinical guidelines from around the world support the prolonged use of secondary preventative medications (e.g., acetylsalicylic acid, second antiplatelet [clopidogrel, prasugrel, and ticagrelor], statin, beta-blocker, and angiotensin blocker). While in-hospital and discharge prescription rates for these essential life-saving medications is excellent, adherence is known to decline within weeks of hospital discharge. This decline in evidence-based medication use was confirmed in a population of patients with coronary artery disease in Ontario (Chapter 3). Furthermore, it was demonstrated that this decline was consistent across all medication classes and subgroups of patients. We developed a protocol (Chapter 4) for a cluster-randomized controlled trial evaluating the impact of repeated reminders sent by mail to the family physician and the patient, starting one month after the STEMI. The fifth chapter highlights the results of the cluster-randomized controlled trial, which demonstrates suboptimal persistence to all 4 of 4 cardiac medication classes at 12-months. There was no significant difference compared to usual care in the use of guideline-recommended medications post-STEMI when participants (and their family physicians) receive repeated postal reminders.

Myocardial infarction (MI) leads to permanent loss of cardiac muscle due to the limited regenerative potential of the mammalian heart. The affected heart muscle is replaced by a fibrotic scar; however, the scar is not able to offset the increase in wall stress placed on the remaining myocardium. This distending pressure can lead to dilative remodeling of the ventricle, progressive loss of cardiac function, and heart failure. Despite current medical therapy, heart failure continues to have a high mortality rate. Therefore, there is a clinical need for treatments that can both improve cardiac function post-MI and reduce ventricular remodeling to prevent progression to heart failure. Injectable biomaterials aim to provide a scaffold to stimulate infarct repair by mimicking the healthy cardiac extracellular matrix (ECM). The ECM plays a critical role in tissue regeneration but after a MI it is pathologically modified. Injection of biomaterials post-MI can provide a scaffold that better stimulates infarct repair. In this study, hydrogels were developed from recombinant human type I and type III collagen (rHCI and rHCIII), the two most prevalent structural proteins in the cardiac ECM. Injection of rHCI and rHCIII hydrogels in a mouse model of MI improved cardiac function and reduced infarct size 28 days post-treatment. Infarcted hearts treated with rHCI exhibited improved myocardial salvage in the region bordering the scar with improved capillary density. rHCI hydrogel was also superior to rHCIII in reducing ventricular remodeling. The injection of rHCI hydrogel into the border zone post-MI resulted in an acute improvement of contractile function two days after treatment that was maintained long-term. At two days post-injection, rHCI treated animals had reduced apoptotic cardiomyocytes and lower levels of oxidative stress. Methylglyoxal modifies and crosslinks collagen in the ECM, leading to oxidative stress. Two days after injection, the rHCI hydrogel at the epicardial surface was modified by methylglyoxal, while methylglyoxal-derived advanced glycation end-product levels in the underlying myocardium were lower than in control animals. It appears that rHCI hydrogel injection is soaking up free methylglyoxal from the myocardium, reducing levels of oxidative stress in cardiac muscle and improving contractility of cardiomyocytes bordering the scar. These results suggest that rHC therapy is a promising approach to improve cardiac contractility, and limit ventricular remodeling post-MI.