Os agentes infecciosos têm sido considerados iniciadores da desestabilização da placa de ateroma. Este mecanismo pode estar relacionado a uma intensificação do processo inflamatório através da interação dos receptores de membrana CD14 e TLR com os microorganismos. Para avaliar esta hipótese, estudou-se a participação da resposta inflamatória induzida por Chlamydophila pneumoniae (Cp) e Mycoplasma pneumoniae (Mp) em indivíduos com infarto agudo do miocárdio (IAM). Avaliou-se também, a possível associação entre polimorfismos dos genes CD14, TLR2, TLR4 e TNFA e a expressão dos genes IL6, TLR2, TLR4 e TNFA em leucócitos do sangue periférico, assim como a sua associação com o IAM. Para isso, foi realizado um estudo caso-controle constituído por pacientes com IAM e por indivíduos sem evidência de doença cardiovascular (grupo controle). As imunoglobulinas IgM e IgG séricas anti-Cp foram detectadas por imunofluorescência indireta. O DNA dos agentes infecciosos foi detectado no sangue periférico pela PCR em tempo real. A genotipagem dos polimorfismos TNFA -308G>A, IL6 -174G>C, CD14 -260C>T, TLR4 (Asp299Gli e Thr39911e) e TLR2 Arg753Gln e a quantificação relativa da expressão gênica nas células sanguíneas foram analisados pela PCR em tempo real. A porcentagem de positividade para DNA de Cp foi de 18,0% e 8,1% nos grupos IAM e controle (p=0,071), respectivamente, (p=0,071). Foram positivos para DNA de Mp, 5,0% e 11,2% dos indivíduos nos grupos IAM e controle, respectivamente (p=0,318). Sete indivíduos (7,1%) do grupo IAM tiveram títulos anti-Cp IgG positivos (1:512) e 3,9% dos indivíduos do grupo controle (p=0,718). A expressão do TLR4 foi significantemente menor no grupo IAM (0,00113±0,00102) comparado ao grupo controle (0,00144±0,000806; p=0,003). As frequências genotípicas e alelicas dos polimorfismos TNFA -308G>A, CD14 -260C>T, TLR4 (Asp299GIi e Thr39911e) e TLR2 Arg753Gln foram similares entre os grupos estudados (p>0,05) sugerindo que esses polimorfismos não estão associados com IAM nesta amostra populacional. No grupo IAM, houve associação entre o genótipo -260CT+TI CD14 com títulos IgG anti-Cp detectados na diluição 1:16 (p=0,042). Da mesma forma, o alelo A do polimorfismo -308G>A TNF-α foi associado com títulos positivos de IgG anti-Cp na diluição 1:512 (p=0,0058). No grupo IAM, pacientes positivos para DNA de Cp tiveram maiores concentrações de fibrinogênio do que pacientes negativos para este agente infeccioso (541,8±161,5mg/dL e 450,5±196,8mg/dL, respectivamente; p=0.043). Os agentes infecciosos Chlamydophila pneumoniae e Mycoplasma pneumoniae não foram significantemente mais frequentes em indivíduos que tiveram infarto agudo do miocárdio em relação ao grupo controle, porém houve uma associação, no grupo IAM, entre positividade para DNA de C. pneumoniae e concentrações mais elevadas de fibrinogênio. / Atheroma plaque instability has been attributed to the presence of some infectious agents. This mechanism may be related with increased stimulus of inflammatory process through interactions of CD14 and TLR with infectious agents. In this present study, it was evaluated the association of the presence of Chlamydophila pneumoniae and Mycoplasma pneumonia with acute myocardial infarction (AMI). A case-control study was conducted with AMI patients and non-AMI individuais as controls. Immunoglobulin G (lgG) and IgM antibodies anti-Chlamydophila pneumoniae were detected by indirect immunifluorescent assay and the Cp DNA and Mp DNA were detected by real time PCR (RT-PCR) in peripheral blood cells. Using the same method, the individuals were genotyped and the gene expressions of TLR2, TLR4, IL-6 e TNF-α were evaluated by RT-qPCR. In AMI patients, Cp DNA and Mp DNA were positive in 18,0% and 5,0% samples, respectively. In controls, 8,1% and 11,2% were positive for Cp DNA and Mp DNA, respectively. TLR4 expression was significantly decreased in AMI patients (0.00113±0.001 02) compared with controls (0.00144±0.000S06; p=0.003). The frequencies of -308G>A TNF-α., -260C>T CD14, Asp299Gli TLR4, Thr39911e TLR4e Arg753Gln TLR2 SNPs in AMI group were similar to those found in controls. On the other hand, In AMI group, the -260CT+TT CD14 genotype was associated with anti-CP IgG antibody titer of 1/16. Likewise, the rare allele of -308G>A TNF-α was associated with anti-CP IgG antibody titer of 1/16. Cp DNA positive patients had high concentration of fibrinogen when compared with negative patients. In conclusion, Cp DNA and Mp DNA positivity were not associated with AMI.

Abstract Several studies have shown that altered cardiovascular autonomic regulation is associated with hypertension, diabetes, aging, angiographic severity of coronary artery disease (CAD), and increased mortality after acute myocardial infarction (AMI). The purpose of this study was to assess the temporal changes and prognostic significance of various measures of heart rate (HR) behaviour and their possible associations to coronary risk variables, and the progression of CAD in different populations. This study comprised five patient populations. The first consisted of 305 patients with recent coronary artery bypass graft surgery (CABG) and lipid abnormalities, the second of 109 male patients with recent CABG, the third of 53 type II diabetic patients with CAD, the fourth of 600 patients with recent AMI, and the fifth of 41 elderly subjects. HR variability and non-linear measures of HR dynamics were analysed. Among the patients with prior CABG, a significant correlation existed between the baseline HR variability (standard deviation of N-N intervals, SDNN) and the progression of CAD (r = 0.26, p < 0.001)). In the longitudinal study of patients with prior CABG, only the fractal indexes of HR dynamics, such as the power law slope (β) and the short-term fractal exponent (α1), decreased significantly. In diabetic patients, SDNN decreased significantly (p < 0.001) during the three-year period. The reduction of SDNN was related to cholesterol, triglyceride, and glucose levels, and also to progression of CAD (r = 0.36, p < 0.01). In the longitudinal follow-up study of patients with recent AMI, reduced fractal indices (α1 and β), and reduced HR turbulence predicted cardiac death when measured at the convalescent phase after AMI. Reduced β and turbulence slope predicted cardiac death when measured at 12 months after AMI. In the elderly population, β (p < 0.001) and α1 (p < 0.01) reduced significantly. Low-frequency power spectra were the only traditional measure of HR variability that decreased significantly during the 16-year period. HR variability is associated with many risk factors of atherosclerosis and with progression of CAD among patients with ischemic heart disease. Fractal HR dynamics are more sensitively able to detect age-related changes in cardiovascular autonomic regulation. Altered fractal HR dynamics and HR turbulence are associated with increased mortality after AMI.

Abstract The development of commercially available assays from the measurement of enzyme activity to mass concentrations of proteins, especially the assays of cardiac troponin I and T, has been the most important innovation in the field of cardiovascular laboratory diagnostics over the decade. The availability of a simple, rapid test using whole blood to facilitate processing and to reduce the turnaround time could improve the management of patients presenting with chest pain. The aim of this study was to evaluate the analytical and clinical performance of a new time-resolved fluorometry-based immunology technology using the cardiac marker and high-sensitivity C-reactive protein assays. In addition, the use of high-sensitivity C-reactive protein assay for the investigation of patients with acute atrial fibrillation and the influence of heparin for cardiac marker assays were studied. The levels of precision attained with pooled serum and plasma samples and control materials were acceptable. The assays were found to be linear within the ranges tested. The correlation coefficient between the Innotrac Aio! 1st generation cTnI and Abbott AxSYM cTnI assays was 0.960, and the slope was 0.07. The correlations between the 2nd generation Innotrac Aio!, Access AccuTnI and Abbott AxSYM assays were good, but there were biases between the methods. The correlation coefficients between the Innotrac Aio! and Abbott AxSYM CK-MB and myoglobin assays were 0.995 and 0.971, respectively, but the Innotrac Aio! CK-MB assay yielded about 9% higher values than the Abbott assay. The correlations between Innotrac Aio! usCRP and Cobas Integra CRP latex and between Innotrac Aio! usCRP and Hitachi CRP (Latex ) HS were good. Furthermore, the sample material correlation studies showed no significant differences when the Innotrac Aio! System was used. However, the mean Abbott AxSYM CK-MB values and the cTnI values for heparin plasma samples were 17% higher and about 15% lower than for serum samples, respectively. In the investigation of CRP levels in patients with acute atrial fibrillation CRP tended to be higher in the patients with acute FA, and there was a positive correlation between the concentrations of CRP and IL-6. The results demonstrate the excellent analytical performance of the Innotrac Aio! 2nd generation cTnI, myoglobin, CK-MB and usCRP assays, and all the matrices, including serum, plasma and whole blood, are suitable sample matrices to be used with these methods without further standardization.

Background: Stem cells are a promising therapy for regeneration following myocardial infarction (MI). Another therapy currently under investigation for MI is glucagon-like peptide-1 (GLP-1), a natural incretin hormone that has cardio-protective properties, although a short half-life in vivo. GLP-1 CellBeads are a novel therapy, combining stem cells and GLP-1. Human mesenchymal stem cells (MSCs) were immortalised, engineered to secrete a fusion protein of GLP-1 and encapsulated in alginate. We have previously demonstrated that GLP-1 CellBeads significantly reduce infarct size and improve ejection fraction post-MI, but the underlying mechanisms are unclear. The therapy was assessed in an in vivo pig MI model and an in vitro cardiomyocyte ischaemia model. Methods: GLP-1 CellBeads were delivered to coronary artery branches in pigs, creating micro-infarcts, as determined by echocardiography. Cell-free beads (Beads) and CellBeads containing hMSCs without GLP-1 (Beads-MSC) were delivered as controls (n=3-5/group). Pigs were sacrificed one and four weeks post-MI. Tissue was analysed for: apoptosis, collagen, cardiomyocyte cross sectional area and myofibroblasts. The localised response around the beads was also measured using immunohistochemistry. Atomic force microscopy (AFM) was used to examine the ultra-structure of the collagen scar. The expression profiles of genes involved in collagen remodelling were measured using qRT-PCR. Viability of MSCs was measured using GFP-tagging and confirmed using qRT-PCR. To examine effects on apoptosis in vitro, human adult cardiomyocytes underwent ischaemia for 1 hour before incubation with: media conditioned with MSCs or MSC+GLP-1, GLP-1, Exendin-4 or media. Apoptosis and viability were measured at 24 and 48 hours respectively. Results: In the in vivo pig model, significant increases in apoptosis were observed in the infarct of all groups one week post-MI, with no differences between treatments. Despite decreased numbers of myofibroblasts, significantly more collagen was observed in MSC treated groups, with increased collagen fibril periodicity and a more organised collagen scar. The altered scar structure was reflected in differences in gene expression between groups, with an accelerated healing response in the MSC groups. However, significantly fewer myofibroblasts were observed in the MSC treated groups. Viability of MSCs was confirmed up to four weeks post-infusion, with GLP-1 secretion confirmed up to one week. In the in vitro ischaemia model, MSC+GLP-1 conditioned media significantly reduced cardiomyocyte apoptosis 24 hours post-ischaemia, compared to media alone. All agonists (GLP-1, MSC media and MSC+GLP-1 media) significantly improved viability compared to media alone 48 hours post-ischaemia. Conclusions GLP-1 CellBeads have a beneficial effect on healing following MI by significantly decreasing infarct size and improving ejection fraction post-MI. these benefits are associated with decreased cardiomyocyte apoptosis and altered collagen scar formation. The CellBeads act as local hubs for regeneration and are viable up to one month post-infusion. The effects observed are due to a combination of the GLP-1 and paracrine factors released from the hMSCs.

The incidence of heart failure (HF) continues to grow despite advances to current therapies which are effective insofar as slowing disease progression. Cardiac stem cell (CSC) therapy is an emerging treatment for the reversal of HF. We sought to examine the effect of genetically engineering CSCs to over-express stromal cell-derived factor 1α (SDF1α) on myocardial repair. SDF1α over-expressing CSCs exhibited a broader paracrine signature resulting in increased stimulation of capillary network formation and chemotaxis under in vitro conditions. Using a murine model of myocardial ischemia, we demonstrated over-expression of SDF1α increased myocardial SDF1α content, reduced scar burden and increased activation of PI3K/AKT signaling as compared to non-transduced CSC and vehicle controls. These effects improved cardiac function without increasing cell engraftment suggesting that the mechanisms driving these benefits are largely paracrine mediated. Taken together this data suggests that transplantation of CSCs genetically programmed to over-express SDF1α provides superior cardiac repair by boosting the content of cardio-protective cytokines during the critical healing phase after myocardial infarction.

Blood-derived circulatory angiogenic cells (CACs) and resident cardiac stem cells (CSCs) have both been shown to improve cardiac function after myocardial infarction (MI) but the superiority of either cell type has long been an area of speculation with no definitive head-to-head trial. In this study, we compared the paracrine profile of human CACs and CSCs, alone or in combination. We characterized the therapeutic ability of these cells to salvage myocardial function in an immunodeficient mouse model of MI by transplanting these cells as both single and dual cell therapies seven days after experimental anterior wall MI. CACs and CSCs demonstrated unique paracrine repertoires with equivalent effects on angiogenesis, stem cell migration and myocardial repair. Combination therapy with both cell types synergistically improves post infarct myocardial function greater than either therapy alone. This synergy is likely mediated by the complementary paracrine signatures that promote revascularization and the growth of new myocardium.

The objective of the dissertation is analysis of costs that are connected with acute myocardial infarction in the Znojmo Hospital. It is about the bill of costs of this diagnosis with the use of analysis "Cost of Illness". Cost of Illness is one of many kinds of analysis examining the costs of illnesses. At work, I have tried to capture all relevant costs of this diagnosis, especially the cost of diagnosis, therapy and hospitalization of patients with the diagnosis of acute myocardial infarction.

Myocardial Infarction: A Study of the Effects On Patient Compliance of Structured Education and Participation of the Significant Other This study was designed to explore the effects of the independent variables of patient education and the significant other on compliance. The purpose of the study was to test three hypotheses predicting that subjects who receive structured education with their significant other would have higher compliance rates with health care recommendations than would subjects who receive structured and unstructured education without their significant other. The study was conducted with a convenience sample of 12 male patients who had a significant other and had not experienced a previous myocardial infarction within five years. The convenience sample was then randomly and equally allocated into three groups. The control group received unstructured education as currently practiced by nursing staff. One experimental group received structured education from the investigator and the other experimental group of subjects and their significant other received structured education from the investigator. Using a semi-structured interview guide, the investigator interviewed each subject at one month and at three to four months postdischarge from hospital to determine compliance rates with physical activity, dietary, and medication health care recommendations as prescribed by the subject's physician. Open-ended questions were used to determine recommendations and difficulties encountered by noncompliers. More specific questions were used to allow subjects to rate their compliance. Results were subjected to the Kruskal-Wallis rank-sum test with one-way analysis of variance. Statistically significant differences (p < .05) were not found suggesting that method of patient education was not a valid prediction of compliant behaviour. The insignificant findings of this study need to be interpreted with caution because of the small sample size and between group differences of the demographic variables of age and employment. From general observations of the total sample, personal definitions of health, simultaneous demands and the extent of behavioural changes required, and the demographic variables of education and employment appear to influence compliance. These findings suggest that individual differences have an impact on compliant behaviour. Findings also suggest that the significant others of patients with myocardial infarctions are actively involved with the therapeutic regimen prescribed for their mates. The study discusses implications and recommendations for nurse practitioners and researchers who wish to improve their care of myocardial infarction patients and their significant others. / Applied Science, Faculty of / Nursing, School of / Graduate

This study involves an investigation of the relationship between dependency and work resumption of patients with myocardial infarction. In the process of studying this problem, information concerning the different levels of dependency during the convalescence through employment continuum v/as gathered. The purposes of the study are to add to the body of knowledge concerning the concept of dependency and to make nurses and other members of the health team aware of the implications of dependency behaviour in the process of resuming normal function of patients with myocardial infarction. Its long range purpose is to increase the sense of well-being and achieving of the patient with myocardial infarction by helping him resume his productive role, both through the help of members of the health team and members of his family. The study was planned to test the following hypotheses: 1. The employed patients with myocardial infarction will show lower dependency ratings than the unemployed patients in the Navran Dy Scale. 2. The employed patients with myocardial infarction will show progressive decrease in the D-I Scale dependency ratings along the convalescence to employment period continuum, while the unemployed patients with myocardial infarction will maintain a constant level of dependency ratings in the D-I Scale along the convalescence to employment period continuum. 3. Low trait dependents with myocardial infarction will show progressive decrease in the D-I Scale dependency ratings along the convalescence to employment period continuum, while high trait dependent patients with myocardial infarction will continue to show steady dependency ratings in the D-I Scale along the convalescence to employment period continuum. Two structured questionnaires were constructed following a review of the literature to obtain information regarding the research problem. The Navran Dy and the dependency portion of the D-I Scale were also administered. The study population consisted of 21 men. The study population was restricted to men who were confined in the hospital for their first myocardial infarction, who were 64 years of age or younger, who could read and write English, and who had been employed for the 6 months immediately prior to the confinement. Analysis of the data included Frequency tables, T test and the Two-Factor Analysis of Variance. The findings of the study showed that patients with myocardial infarction showed different degrees of dependency, both trait and state. The findings failed to support the three hypotheses even though during the data analysis of the individual hypothesis, the group means showed leaning towards the direction of the hypothesis. The study suggests that steps should be taken to make nurses and family more aware of the varying degrees of dependency in patients. / Applied Science, Faculty of / Nursing, School of / Graduate

Transmyocardial revascularization (TMR) has emerged as an additional therapeutic option for patients suffering from diffuse coronary artery disease (CAD), providing immediate angina relief. The current potential of this therapy focuses on the injection of stem cells, in order to create a synergistic angiogenic effect while increasing myocardial repair and regeneration. Although TMR procedures provide increased vascularization within the myocardium, patients suffering from ischemic cardiomyopathy may not benefit from angiogenesis alone. Therefore, the goal of introducing stem cells is to restore the functional state of a failing heart by providing stem cells with a favorable microenvironment that will enhance their engraftment. Since the therapeutic effect of stem cells is dependent on their capacity to survive and retain in the myocardium, laser therapy may provide a strategy for increasing stem cell engraftment. If so, these cells may have the potential to act as mitochondrial donors or as sources of paracrine factors, aiding in the recovery from oxidative stress and providing antioxidant reserves. Furthermore, laser therapy may also play an influential role in regulating cardiac repair and regeneration via epithelial-mesenchymal transition (EMT). By interacting with specific transcription factors TMR may provide another pathway by which it can offer reparative effects. Cumulatively, paracrine release, denervation, and angiogenesis contribute to the therapeutic benefits experienced by TMR patients, including a significant reduction in angina, with increases in myocardial perfusion and survival rates. With the addition of stem cells, these effects may be further augmented, thus providing increased symptomatic relief in patients.