Thesis--Columbia University. / Photocopy of typescript. Ann Arbor, Mich. : University Microfilms International, 1977. -- 21 cm. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 160-168).

Thesis (M.S.)--University of Wisconsin. School of Nursing, 1976. / eContent provider-neutral record in process. Description based on print version record.

Thesis (D.N. Sc.)--Catholic University of America, 1974. / Includes bibliographical references (leaves [181]-217).

Thesis (Ph. D.)--University of Rhode Island, 2006. / Includes bibliographical references (leaves 181-201).

Made available in DSpace on 2014-06-11T19:32:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-12-20Bitstream added on 2014-06-13T19:02:37Z : No. of bitstreams: 1 farah_e_dr_botfm.pdf: 474289 bytes, checksum: e469a5b37f90ddb14b6d4798544086d8 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O infarto agudo do miocardio (IAM)é responsável por grande número de óbitos e hospitalizações em todo o mundo. O prognóstico pós-infarto está associdado a diversos fatorews como idades, sexo, tamanho do infarto, presença de comorbidades. Vem ganhando destaque na literatura, como fator de má evolução pós-IAM, a remodelação ventricular que, clinicamente, caracteriza-se por aumento da cavidade ventricular. O objetivo princiap foi avaliar a relação entre o padrão do supradesnivelamento do segmento ST e a remodelação ventricular após infarto agudo do miocárdio de parede anterior do ventrículo esquerdo (VE). Adicionalmente, avaliar a prevalência, as características clínicas e identificar novas variáveis preditoras de remodelação ventricular em tempos de terapia médica agressiva após o infarto. Estudo prospectivo, longitudinal, observacional, realizado na Unidade Coronária do Hospital das Clínicas da Faculdade de Medicina de Botucatu no período de novambro de 2007 a maio de 2010. Foram avaliados 76 pacientes com IAM de parede anterior do VE. Destes 3 foram excluídos por apresentarem fibrilação... / The acute myocardial infarction (AMI) is responsible for a great number of deaths and hospitalizations aroud the world. The prognostic after acute myocardial infarction is associated to many factors such as age, sex, size of myocardial infarciton, presence of other diseases. In the last years, another variable studied as a predictor of porr outcime after MI is ventricular remodeling, characterized by increased ventricular cavity. To evaluate the relationship between ST segment elevation pattern and ventricular remodeling after anterior wall AMI of left ventricular was the main goal of this work. In addition, we analyzed the prevalence, clinical characteristics, and predictors of left ventricular remodeling in the era of modern medical therapy. Seventy sic patients with anterior wall AMI were evaluated from november 2007 to may 2010. There patients with atrial fiblilation and one with severe valvar diseases were excluded. During the follow-up period, six patients died. Thus, the clinical characteristics, patterns... (Complete abstract click electronic access below)

Abstract The prevalence of coronary heart disease (CHD) and associated manifestations with ischaemic resting electrocardiogram (ECG) changes, clinical findings and sociodemographic factors were studied in 1990–1991 among an elderly population in southwestern Finland. One of the specific aims was to describe the health-related quality of life of elderly coronary heart disease patients, i.e. the associations between CHD and physical, psychological, cognitive and social functioning. 488 men and 708 women aged 64 years and over (93% of those eligible) participated in this cross-sectional epidemiological survey in the rural district of Lieto. The participants were examined and interviewed during two visits to the local health centre. An ECG and a chest x-ray were taken and a clinical examination was made by a doctor. The Rose questionnaire was used to determine the prevalence of angina pectoris (AP). The Minnesota codes were used in the analyses of ECG findings. The medical records were reviewed. The prevalence of AP was 9.1% (95% Confidence Interval 6.7–12.0) among men and 4.9% (3.5–6.8) among women. The respective figures for past myocardial infarction (MI) (based on the medical records or a major or moderate Q/QS item on ECG, codes 1.1–1.2) were 13.9% (10.9–17.0) and 6.5% (4.8–8.6). Ischaemic ECG findings (codes 1.1–1.3, 4.1–4.4, 5.1–5.3, 7.1) were common: 32.9% (28.7–37.1) of men and 39.3% (35.7–43.0) of women had such changes. The total prevalence of CHD, including AP, MI, past coronary bypass surgery or angioplasty or ischaemic ECG findings, was 37.7% (33.4–42.0) in men and 42.0% (38.3–45.6) in women. The patients and controls were mainly aged, non-institutionalized, community-living persons. The patients with CHD (AP and/or a past MI) had more difficulties in physical functioning than their age- and sex-matched controls. According to logistic regression analyses, CHD was not independently associated with difficulties in physical functioning. However, physical disability was associated with the use of cardiovascular drugs and also with old age, the use of psychotropic drugs, depression and cancer. More male patients than controls had depression measured on the Zung Self-Rating Depression Scale. The depression had often gone undiagnosed, especially among men. Among men, the most important factors associated with depression were difficulties in physical functioning and widowhood or divorce, while among women, previous depression and the use of ACE inhibitors emerged as significant. There were no differences between the patients and controls in cognitive functioning. The male patients had a higher frequency in visiting activity than the controls. Old age, difficulties in physical functioning, CHD and chronic obstructive pulmonary disease were associated with impaired social functioning. In conclusion, CHD is common in the Finnish elderly. The clinical picture of CHD in elderly people is varying. It seems that CHD has no independent impact on functional disability in the elderly. Old age, sociodemographic factors, medication and other chronic diseases are also contributors.

Abstract Ischemic stroke is associated with cardiovascular autonomic nervous system (ANS) disturbances, including reduced heart rate (HR) variability and acute phase neurohumoral activation with elevated stress hormone levels. The impact of HR variability and neurohumoral factors such as natriuretic peptides on the long-term survival of patients with ischemic stroke has not been studied previously. This study was designed to evaluate cardiovascular autonomic regulation in ischemic stroke patients by assessing HR dynamics and various neurohumoral factors. The values of the assessed variables in predicting mortality were evaluated. HR variability assessments were performed in the acute phase of ischemic stroke and for a general elderly population. Various neurohumoral factors were also assessed in the acute phase of stroke. After follow-up, the survival of the subjects was assessed and the prognostic values of the measured factors were evaluated. Stroke patients were found to have cardiovascular autonomic and hormonal disturbances manifested as reduced traditional time and frequency domain measures of HR variability, altered long-term HR dynamics and elevated levels of natriuretic peptides in the acute phase. Altered long-term HR dynamics in the acute phase of stroke predicted long-term mortality after stroke and cerebrovascular mortality in the general elderly population. Neuroendocrine activation involving elevated natriuretic peptide values that were associated with high cortisol and catecholamine levels was observed in the acute phase of ischemic stroke. Neurohumoral disturbance was prognostically unfavourable. The most powerful predictors of poststroke mortality were altered long-term HR dynamics and elevated levels of natriuretic peptides and cortisol, which predicted mortality independently of the conventional risk factors in multivariate analysis. Prognostically unfavourable cardiovascular autonomic dysfunction with disturbances in the long-term behaviour of HR dynamics was found to be related to ischemic stroke. Neurohormonal activation with elevated natriuretic peptide and cortisol levels in the acute phase predicts long-term mortality after ischemic stroke.

Ischaemic heart disease accounts for approximately 7 million deaths worldwide on a yearly basis and this figure is only set to rise as life expectancy in developing countries increases. Although no longer considered a post mitotic organ, the adult heart demonstrates only a very limited capacity for regeneration. Consequently ischaemic injury results in massive loss of contractile cardiomyocytes with damaged myocardium replaced by a non-contractile and poorly conductive collagen scar. This in turn often leads to the development of heart failure. Enhancing or supplementing the myocardial regenerative capacity of the heart is thus a key goal in the development of effective therapies for the treatment of cardiac infarction. Several stem cell populations of non-cardiac origin have been investigated for their capacity to contribute to myocardial repair when therapeutically transplanted into injured hearts. Recent efforts have focused on the “next generation” of donor cells, endogenous cardiac progenitor cells, as these are thought to be better adapted to survival in the cardiac environment and to possess enhanced cardiomyocyte differentiation potential. Pericytes, proposed as the source of the elusive mesenchymal stem cells (MSC) within multiple tissues, are a potential new cell type for use in regenerative medicine. This study tests the hypothesis that pericytes and another perivascular progenitor population, the adventitial cell, from foetal cardiac tissue will positively contribute to the repair of the myocardium post injury. Staining of human foetal ventricular myocardium confirmed the presence of large numbers of both cell types with pericytes tightly associated with capillaries and adventitial cells primarily located in the outer, adventitial layer of muscular arteries. CD146+ CD34- pericytes and CD146- CD34+ adventitial cells were isolated by FACS and expanded in culture. On examination of gene and protein expression both populations stably expressed a similar panel of pericyte markers, MSC markers and cardiac transcription factors as well as c-kit, a cardiac progenitor cell candidate marker. Co-culture with neo-natal rat cardiomyocytes induced expression of an additional cardiac progenitor marker Isl-1 and a mature cardiomyocyte marker ANP in adventitial cells but not pericytes. Labelled, co-cultured, perivascular progenitors readily adhered to rat cells but did not appear to contract independently. De-methylation of perivascular progenitors prior to co-culture resulted in expression of sarcomeric proteins and spontaneous cytoplasmic calcium fluctuations in both populations but more commonly in pericytes. This suggests that cardiac perivascular cells contain a minor sub-population capable of cardiomyocyte differentiation. When these populations were injected into the infarcted hearts of NOD/SCID mice, the animals treated with adventitial cells had significantly reduced cardiac function at 21 days post-surgery on ultrasound examination. An increased scar area and a non-significant trend towards increased scar length and a decreased wall thickness were also observed. Transplanted cells of both groups were detected in low numbers 21 days after injection. Adventitial cells were retained much more readily and in both populations retained cells exhibited three key morphologies: fibroblast type; macrophage type; and cardiomyocyte type. The majority of cells adopted a fibroblast type morphology, lesser numbers a macrophage like morphology and only rare cells a cardiomyocyte like morphology. Both fibroblast and cardiomyocyte type cells had single, human nuclear antigen positive nuclei suggesting true differentiation rather than cell fusion and pericytes exhibited an enhanced ability to differentiate into cardiomyocytes. This supports the in-vitro findings of a minor pro-cardiomyogenic subset within the perivascular cell population. As a result of these findings the starting hypothesis was modified to propose that perivascular cells play a significant role in cardiac fibrosis, largely mediated through expression of surface integrin receptors. This was tested using mice expressing fluorescent proteins under the control of the PDGFR-β promoter and mice in which the αv integrin subunit, common to 5 integrin receptors, had been deleted on the surface of PDGFR-β+ cells. Immunostaining and flow cytometry revealed the PDGFR-β expression to be tightly restricted to perivascular cells and co-expressed with the fibroblast markers, vimentin, PDGFR-α, CD90.2 and CD34 in a subset of cells. Cardiac fibroblasts isolated from reporter mouse hearts revealed strong expression of PDGFR-α and CD34 but PDGFR-β expression in only approximately 20% of the population on flow cytometry. Following angiotensin II induced cardiac hypertrophy and fibrosis approximately 50% of fibroblasts expanding the interstitium were PDGFR-β+. Genetic deletion of the αv integrin subunit on PDGFR-β+ cells resulted in a reduction in cardiac interstitial collagen content of about 50% compared to wild type controls. These findings suggest that the cardiac perivascular PDGFR-β+ population is heterogeneous with a sub-population likely to be fibroblasts or fibroblast progenitors and that the development of cardiac interstitial fibrosis is in part modulated by integrin receptor expression on these cells. In summary this study provides evidence of the existence of a pro-fibrotic progenitor population, which co-express pericyte and MSC markers, within the cardiac perivascular niche. These cells contribute to cardiac fibrosis both on transplantation and endogenously following cardiac injury with the latter mediated via αv integrin expression. Within the perivascular progenitor population however there also appears to be a minor subset of pro-cardiomyogenic cells which are able to adopt a cardiomyocyte phenotype both in-vitro and in-vivo.

Despite advances in treatment, heart failure remains one of the top killers in Canada. This recognition motivates a new research focus to harness the fundamental repair properties of the human heart, with human cardiac stem cells (CSCs) emerging as a promising cell candidate to regenerate damaged myocardium. The rationale of this approach is simple with ex vivo amplification of CSCs from clinical grade biopsies, followed by delivery to areas of injury, where they engraft and regenerate the heart. Currently, outcomes are limited by modest engraftment and poor long-term survival of the injected CSCs due to on-going cell loss during transplantation. As such, we explored the effect of cell encapsulation to increase CSC engraftment and survival after myocardial injection. Transcript and protein profiling of human atrial appendage sourced CSCs revealed strong expression the pro-survival integrin dimers αVβ3 and α5β1- thus rationalizing the integration of fibronectin and fibrinogen into a supportive intra-capsular matrix. Encapsulation maintained CSC viability and expression of pro-survival transcripts when compared to standard suspended CSCs. Media conditioned by encapsulated CSCs demonstrated superior production of pro-angiogenic/ cardioprotective cytokines, angiogenesis and recruitment of circulating angiogenic cells. Intra-myocardial injection of encapsulated CSCs after experimental myocardial infarction favorably affected long-term retention of CSCs, reduced scar burden and improved overall cardiac function. Taken together, cell encapsulation of CSCs prevents detachment induced cell death while boosting the mechanical retention of CSCs to enhance repair of damaged myocardium.

MicroRNAs are emerging as key players in the regulation of the post-myocardial infarction (MI) environment. We previously identified that matrix-treated hearts had down-regulated expression of miR-92a, a miRNA with inflammatory and migratory effects that is normally up-regulated after MI. We have shown that type I collagen matrix treatment at 3h post-MI leads to less inflammation and improved cardiac function, but the underlying mechanisms remain to be better characterized. The goal of this study was to elucidate a possible role of miR-92a in the anti-inflammatory/pro-wound healing effect of matrix treatment post-MI. C57BL/6J mice underwent LAD ligation to induce MI. Hearts were removed at 4h, 1d, 3d, and 7d post-MI and RNA was extracted from infarct and peri-infarct tissue. PCR analysis revealed that hearts injected with matrix at 3h post-MI resulted in significantly decreased miR-92a at 4h, 1d, and 3d compared to non-injected animals at each time point (p<0.0001) and PBS injected animals at 4h and 7d (p<0.004). Several targets of miR-92a and regulators of macrophage polarization were found to be up-regulated (p<0.05) early in MI indicating early amelioration of inflammatory processes. In vitro, macrophages cultured on matrix also had decreased expression of miR-92a compared to cultures on tissue culture poly styrene (TCPS) (p<0.001). Integrins α5 (ITGAα5) and αV (ITGAαV), involved in cell-matrix interactions, as well as inflammatory regulators S1PR1 and SIRT1 were identified as putative miR-92a targets. When miR-92a is over-expressed in macrophages, ITGα5 (p=0.0002), ITGαV (p=0.02), and S1Pr1 (p<0.0001), and SIRT1 (p=0.03) all had decreased expression. STAT3 and IL-10 were found to be moderately down-regulated. In evaluating macrophage phenotypes, M2 macrophages had reduced miR-92a expression on matrix compared to M1 macrophages. The migration of M2 macrophages into the matrix is increased compared to M1 macrophages. We report that the beneficial effects of matrix treatment post-MI may be mediated, at least in part, through its ability to regulate miR-92a and pro-wound healing mechanisms in macrophages. These results present the matrix as a novel non-pharmacological approach to locally regulate miRNAs in vivo for reducing inflammation and protecting the myocardium post-MI.