Orientador: Sergio Alberto Rupp de Paiva / Resumo: A remodelação cardíaca tem papel importante na disfunção ventricular pósinfarto. Alguns mecanismos como estresse oxidativo, metabolismo energético e processo inflamatório modulam este processo. Neste contexto, há interesse em utilizar alimentos naturais, com propriedades antioxidantes e anti-inflamatórias, destacando-se o açaí (Euterpe oleracea Mart). Objetivo: Avaliar a influência da suplementação de açaí na ração sobre a remodelação cardíaca após o infarto do miocárdio (IM) em ratos. Métodos: Ratos Wistar machos, com peso entre 200-250g, foram submetidos ao infarto experimental ou à cirurgia simulada (Sham) e alocados em seis grupos após estudo ecocardiográfico, para verificar o tamanho do infarto: 1) grupo Sham alimentado com ração padrão (SA0, n=14); 2) grupo Sham alimentado com ração padrão suplementada com 2% de polpa de açaí pasteurizado (SA2, n=13); 3) grupo Sham alimentado com ração padrão suplementada com 5% de polpa de açaí pasteurizado (SA5, n=14); 4) grupo infartado alimentado com ração padrão (IA0, n=12); 5) grupo infartado, alimentado com ração padrão suplementada com 2% de polpa de açaí pasteurizado (IA2, n=12); 6) grupo infartado, alimentado com ração padrão suplementada com 5% de polpa de açaí pasteurizado (IA5, n=12). Os animais foram suplementados por três meses e foi observada a mortalidade. Após esse período, os animais foram submetidos à segunda avaliação ecocardiográfica e posteriormente à eutanásia e coleta de material biológico para realização das de... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Cardiac remodeling plays a key role in post-infarction ventricular dysfunction. Some mechanism, such as oxidative stress, energy metabolism and inflammation can modulate this process. In this context, there is great interest in natural foods, with antioxidant and anti-inflammatory properties, as açaí (Euterpe oleracea Mart). Objective: To analyze the influence of açaí supplementation in chow on cardiac remodeling after myocardial infarction (MI) in rats. Methods: Male Wistar rats with 200-250 g, were submitted to the experimental infarction or simulated surgery and divided into six groups: 1) Sham group fed standard chow and not subjected to the IM (SA0, n=14); 2) Sham group fed standard chow supplemented with 2% açaí pulp pasteurized and not subjected to IM (SA2, n=13); 3) Sham group fed standard chow supplemented with 5% açaí pulp pasteurized and not subjected to IM (SA5, n=14); 4) group submitted to MI and fed standard chow (IA0, n=12); 5) group submitted to MI and fed standard chow supplemented with 2% açaí pulp pasteurized (IA2, n=12); 6) group submitted to MI and fed standard chow supplemented with 5% açaí pulp pasteurized (IA5, n=12). The animals were supplemented for three months and observed mortality. After this period, the animals underwent echocardiography and subsequently euthanized and collecting biological material for other evaluations. The values were expressed as mean ± standard error. The comparisons were made by two-way ANOVA test with significance level o... (Complete abstract click electronic access below) / Mestre

FundaÃÃo de Amparo à Pesquisa do Estado do Cearà / A Alpinia zerumbet à uma planta popularmente utilizada no tratamento da hipertensÃo arterial sistÃmica e ansiedade. Estudos, principalmente com o Ãleo essencial da Alpinia zerumbet (OEAz), demonstraram aÃÃes hipotensoras, vasodilatadoras, antioxidantes, entre outras. Assim, o objetivo deste estudo à analisar o efeito do OEAz na funÃÃo cardiovascular e autonÃmica em ratos com infarto agudo do miocÃrdio(IAM) induzido por isoproterenol. Utilizaram-se ratos Wistar machos, pesando entre 250-350 gramas distribuÃdos em quatro grupos: Controle, Ãgua por gavagem durante 7 dias e salina subcutÃnea nos dias 6 e 7; ISO, Ãgua por gavagem 7 dias e isoproterenol 150mg/kg nos dias 6 e7; OEAz, OEAz 100mg/kg por gavagem 7 dias e salina subcutÃnea nos dias 6 e 7; ISO+OEAz, OEAz 100mg/kg por gavagem 7 dias e isoproterenol subcutÃneo dias 6 e 7. A pressÃo arterial(PA) e frequÃncia cardÃaca(FC) foram medidas por catÃter de pressÃo na aorta abdominal. O Eletrocardiograma foi registrado utilizando-se derivaÃÃo DII. Inseriu-se uma cÃnula de polietileno na veia cava, para administraÃÃo dos fÃrmacos fenilefrina(0,5; 1 e 2ug/kg) e nitroprussiato de sÃdio(5, 10 e 20ug/kg) para avaliar os barorreflexos, serotonina(2, 4 e 16ug/kg) para avaliar os receptores cardiopulmonares e atropina(3mg/kg) e propranolol(4mg/kg) para avaliar os sistemas simpÃtico e parassimpÃtico. A Variabilidade da FrequÃncia CardÃaca(VFC) foi derivada do intervalo de pulso e a Variabilidade da PA(VPA) da PAS. O coraÃÃo dos animais foram fatiados e corados com TTC para avaliaÃÃo da Ãrea de infarto. Em relaÃÃo aos parÃmetros cardiovasculares foi significantemente maior a FC e o trabalho cardÃaco do grupo OEAz quando comparado ao ISO. Quanto ao eletrocardiograma o intervalo RR foi menor no grupo OEAz comparado ao ISO, a duraÃÃo do complexo QRS foi maior nos grupos ISO e OEAz+ISO comparadas ao Controle e no grupo ISO comparado com o OEAz, o intervalo QT foi maior nos grupos ISO e OEAz+ISO comparados com o Controle e com o OEAz assim como no intervalo QTc, a onda Q foi mais profunda no grupo OEAz+ISO comparados com o Controle e OEAz, a onda R foi maior no grupo Controle comparado com os demais, a onda T e o segmento ST foram maiores nos grupos ISO e OEAz+ISO comparados com o Controle e OEAz. A mÃdia VFC no domÃnio do tempo foi maior no grupo ISO comparado ao OEAz e OEAz+ISO, o mesmo ocorreu na VFC no domÃnio da frequÃncia na banda de baixa frequÃncia. A VPA na banda de alta frequÃncia foi maior no grupo OEAz comparado com o ISO. O reflexo cardiopulmonar mostrou significÃncia na variaÃÃo da PA da dose intermediÃria de serotonina comparada com as demais, e na variaÃÃo da FC do grupo Controle comparado com OEAz+ISO. A FC intrÃnseca foi menor no grupo ISO comparado com o Controle e o Ãndice simpÃtico-vagal maior no grupo ISO que no Controle. NÃo houve diferenÃa significante na extensÃo do infarto nos grupos ISO e OEAz+ISO. Conclui-se que o prà tratamento com o OEAz nÃo foi capaz de reverter os danos hemodinÃmicos e eletrocardiogrÃficos mas reverteu o aumento da modulaÃÃo simpÃtica causados pelo IAM.

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Aproximadamente 5% dos pacientes com infarto agudo do miocÃrdio tÃm idade inferior a 45 anos. As caracterÃsticas especÃficas, epidemiolÃgicas e clÃnicas desta populaÃÃo ainda nÃo estÃo bem esclarecidas. O objetivo do presente estudo à caracterizar a apresentaÃÃo clÃnica, epidemiolÃgica e cinecoronariogrÃfica em jovens submetidos à angioplastia coronariana primÃria (ATC). Foi realizada uma anÃlise retrospectiva de 150 prontuÃrios de pacientes com idade inferior a 45 anos submetidos à ATC entre janeiro de 2006 e dezembro de 2010. Foram analisados os fatores de risco, a apresentaÃÃo clÃnica e eletrocardiogrÃfica, a funÃÃo ventricular esquerda, caracterÃsticas da anatomia coronariana, o tratamento mÃdico e a evoluÃÃo hospitalar. Observou-se que a idade mÃdia dos pacientes foi de 40,1 Â5 anos, com predominÃncia do sexo masculino (68,7%). Os fatores de risco mais associados com o IAM foram o tabagismo (65%), a hipertensÃo arterial sistÃmica (50%), a histÃria familiar de doenÃa arterial coronariana (40%) e os baixos nÃveis de HDL - colesterol (60%). A prevalÃncia de diabetes mellitus foi de 19,3%. O acometimento da artÃria descendente anterior (DA) ocorreu em 53% dos indivÃduos e em 75% foi observada doenÃa em uma Ãnica artÃria. O tempo mÃdio de chegada ao hospital apÃs o inÃcio dos sintomas (delta T) foi de 5,5  3,4 horas e a permanÃncia hospitalar foi de 10,36  14,1 dias. Em 58% dos pacientes, a fraÃÃo de ejeÃÃo do ventrÃculo esquerdo foi superior a 55%. Houve apenas um Ãbito. A taxa de sucesso da ATC foi de 91%. Quanto ao tratamento do IAM, os pacientes receberam globalmente Ãcido acetilsalicÃlico (99,3%), clopidogrel (98%), inibidores da enzima de conversÃo da angiotensina (IECA) (85,3%), betabloqueadores (66%), estatinas (97,3%) e a prescriÃÃo de inibidores da glicoproteÃna IIb-IIIa foi observada em somente 10% dos pacientes. ConcluÃmos que o IAM em jovens apresenta-se como uma entidade tipicamente masculina e de bom prognÃstico na evoluÃÃo precoce, desde que instituÃdo tratamento adequado em tempo hÃbil. O tratamento mÃdico destinado a estes pacientes no Hospital de Messejana Dr. Carlos Alberto Studart Gomes contempla o que à proposto pela IV Diretriz Brasileira para tratamento do IAM com supradesnivelamento do segmento ST. / Approximately 5% of patients with acute myocardial infarction under the age of 45 years. The specific characteristics, clinical and epidemiological this population are not well understood. The aim of this study is to characterize the clinical, epidemiological and coronary cineangiography in young people undergoing primary coronary angioplasty (PTCA). We performed a retrospective analysis of 150 medical records of patients under the age of 45 years who underwent PCI between January 2006 and December 2010. We analyzed the risk factors, clinical presentation and electrocardiographic left ventricular function, characteristics of the coronary anatomy, medical treatment and hospital course. It was observed that the average age of patients was 40.1  5 years, predominantly male (68.7%). The risk factors associated with AMI were smoking (65%), hypertension (50%), family history of coronary artery disease (40%) and low levels of HDL - cholesterol (60%). The prevalence of diabetes mellitus was 19.3%. Involvement of the anterior descending artery (AD) occurred in 53% of individuals and 75% was observed in the disease in a single vessel. The average time of arrival at the hospital after symptom onset (delta T) was 5.5  3.4 hours and hospital stay was 10.36  14.1 days. In 58% of patients, the ejection fraction of left ventricle was greater than 55%. There was one death. The success rate of PTCA was 91%. Regarding the treatment of AMI patients received aspirin overall (99.3%), clopidogrel (98%), angiotensin-converting enzyme inhibitors (ACEI) (85.3%), beta blockers (66%), statins ( 97.3%) and prescription of glycoprotein IIb-IIIa was observed in only 10% of patients. We conclude that in young AMI presents itself as an entity typically masculine and good prognosis in early evolution, provided that appropriate treatment instituted in a timely manner. Medical treatment for these patients at the Hospital of Messejana Dr. Carlos Alberto Studart Gomes contemplates what is proposed by the IV Brazilian Guideline for the treatment of AMI with ST-segment elevation

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.