Background: Myocardial infarction (MI) results in severe biochemical, physiological, and cellular changes that lead to alterations in the structure and function of the myocardium. Oxidative stress potentiates this remodeling response and is associated with progressive worsening of cardiac function. Accordingly, we used a powerful antioxidant-based therapeutic strategy to improve cardiac health and study redox-dependent signaling. Methods: MI was surgically induced in rats by ligating the left anterior descending coronary artery. Subgroups of MI rats received resveratrol (i.p., 10 mg/kg/day for 28 days beginning immediately post-MI). Cardiac histology and biochemical analyses of genes and proteins implicated in cardiac fibrosis, hypertrophy, and apoptosis, and redox-dependent signaling were analyzed. Results: As expected, MI resulted in profound structural changes to the myocardium. Further, we observed a sharp reduction in nuclear factor-erythroid 2-related factor 2 (Nrf2) and Krüppel-like factor 15 (KLF15), factors that are responsible for maintaining the endogenous antioxidant capacity and regulating cardiac gene expression, respectively. It is likely that disruption of normal KLF15 signaling permitted the expression of several cardiac genes associated with progressive cardiac remodeling. Importantly, daily treatment with resveratrol ameliorated cardiac remodeling, improved redox state, restored Nrf2 expression, and up-regulated KLF15 expression. Further, induction of KLF15 signaling following resveratrol treatment is associated with attenuated expression of several genes implicated in cardiac remodeling. Conclusions: Chronic oxidative stress potentiates cardiac remodeling post-infarct, in part, by suppressing Nrf2 and KLF15 expression. Importantly, we demonstrate that normal KLF15 signaling may be rescued with an antioxidant-based therapy, which may be an attractive therapeutic target to support cardiac health post-MI.

ECG warning system is established for real time monitoring of a patient's electrocardiogram (ECG) and automatic detection of certainement cardiac diseases, namely myocardial infarction, hyperkalemia and atrioventricular block. A distinctive research work related on the assimilation of modern technologies: software, computer and information technologies. ECG early warning system's algorithm is developed in accordance to measuring the average of the ECG signatures and Interprets the data with simulated healthy curve. The prototype system INITIALLY classifies the data and Evaluated it with natural healthy simulated curve. Meanwhile the system discards f healthy curve exists otherwise the system stores the distinguished abnormalities in the curve then transfers Warning to the doctor and patient. Cardiac patients can be assisted by this warning system by detecting abnormalities at the very early stage. Consequently, doctors Provide better tools to identify cardiac diseases resulting things more accurate medical advice

The present research compared the psychosocial responses of Type A and Type B individuals following myocardial infarction. Differences in self-referential style and responsiveness to an uncontrollable event were of interest. Thirty-three post-MI patients were followed over a three month period. Self-report measures were administered at two weeks, one month, and three months post-MI to assess levels of psychosocial adjustment and factors associated with adjustment. Type A individuals were more self-involved and reported a greater frequency of negative self-statements following the heart attack. They appeared more depressed, reported more symptoms, had lower expectancies for success, and were hypersensitive to a perceived lack of control relative to Type B's. They resumed activities sooner, but delayed their return to work. No differences between the two groups were found on measures of information seeking, medical compliance, health locus of control, or life satisfaction. The results were discussed with reference to previous research on the Type A behavior pattern and implications for cardiac rehabilitation were presented.

No description available.

Myocardial infarction (MI) is primarily caused by blockade of the coronary circulation, resulting in ischemic insult. The only available remedy is reperfusion, which induces oxidative stress and activates inflammatory responses at the site of injury. Cysteinyl leukotrienes (cysLTs) are potent pro-inflammatory mediators that exert their effects through two classical receptors: cysLT receptor 1 (CysLT1R) and cysLT receptor 2 (CysLT2R), the latter of which is prevalent in the heart and circulatory system and has been implicated in cardiovascular disease. However, although endothelial CysLT2R overexpression exacerbates MI damage and induces vascular hyperpermeability, understanding of CysLT2R activation-induced mechanisms is poor, as isolating CysLT2R-specific effects has proven difficult due to a lack of appropriate pharmacological agents. We investigate herein the role of CysLT2R activation in myocardial ischemia/reperfusion injury. We have characterized a novel CysLT2R-selective antagonist BayCysLT2 in both in vitro and in vivo systems, and establish that CysLT2R-selective antagonism attenuates exacerbated MI injury, adhesion molecule gene regulation, and myocardial neutrophil presence observed in CysLT2R overexpressing (EC) mice. We also examined effects of CysLT2R antagonism in long-term cardiac remodeling post-myocardial infarction, and found that blockade of CysLT2R post-reperfusion, regardless of whether CysLT2R is overexpressed or not, elicits a mild pathological cardiac hypertrophic response despite mitigating infarction damage to the apical ventricular wall. Finally, we created a novel mouse model (EC/KO) that expresses CysLT2R predominantly in vascular endothelium in order to identify tissue-specific mechanisms of CysLT2R activation. Surprisingly, MI injury was attenuated in EC/KO mice, indicating that both endothelial and non-endothelial CysLT2R expression subsets have roles in mediating infarction injury. Indeed, EC/KO mice demonstrated hyperpermeability in cremaster venules only when leukotrienes are applied, in contrast to EC mice. In addition, endothelial CysLT2R activation facilitates leukocyte transmigration, whereas non-endothelial CysLT2Rs regulate basal rolling leukocyte flux in microvasculature. Although much work remains to be done, the characterization of a CysLT2R-selective antagonist provides a vital tool for CysLT2R research moving forward, and our investigation of CysLT2R activation reveal the existence of a complicated and multi-faceted pathway resulting in activation of pro-inflammatory mechanisms. / Thesis (Ph.D, Physiology) -- Queen's University, 2013-09-26 10:29:03.466

Le remodelage ventriculaire gauche (RVG) est un processus complexe qui intervient après un infarctus du myocarde chez 30% des patients en dépit des meilleurs traitements connus actuellement. Le but de mon travail de thèse consistait à identifier les déterminants moléculaires du RVG dans le but de mieux en comprendre les mécanismes physiopathologiques. Pour cela, nous avons étudié les modifications post-traductionnelles des protéines contractiles du VG et en particulier, la phosphorylation et la O-N-acétylglucosaminylation (O-GlcNAc). Nous nous sommes ensuite particulièrement intéressés à la troponine T (TnT) pour laquelle nous avons ainsi pu mettre en évidence une diminution de la phosphorylation au niveau de la sérine 208 au niveau du VG et du plasma chez le rat, suggérant que cela pourrait être un marqueur du RVG post-infarctus. Pour cette étude, nous avons travaillé en collaboration avec l’unité INSERM U644 de Rouen sur un modèle expérimental d’insuffisance cardiaque. L’infarctus du myocarde est induit chez le rat par ligature de la branche descendante de l’artère coronaire gauche, les rats témoins subissant l’intervention mais sans ligature. Dans un premier temps, nous avons réalisé une étude globale du phosphoprotéome du VG en phase tardive du RVG (2 mois post-ligature). Pour cela, les protéines extraites du VG ont été séparées par électrophorèse bidimensionnelle puis colorées au Pro-Q®Diamond (spécifique des protéines phosphorylées) puis au Sypro®Ruby (spécifique des protéines totales). Par analyse bioinformatique, nous avons mis en évidences 69 spots polypeptidiques présentant des modulations de phosphorylation. Nous avons donc analysé ces spots par spectrométrie de masse et avons identifié 30 protéines correspondant à 53 spots polypeptidiques présentant des modulations de phosphorylation. Parmi ces protéines, nous avons choisi de nous concentrer et d’étudier 6 protéines contractiles : la TnT, l’alpha-tropomyosine 1 (α-Tm 1), la desmine, l’αB-crystalline et les chaînes légères de myosine 1 et 2 (MLC). Pour chacune de ces protéines, nous avons identifié le type d’acide aminé responsable de la phosphorylation et quantifié les modulations de phosphorylation dans le VG des rats insuffisants cardiaques (IC). De manière intéressante, nous avons observé que le VG des animaux IC présentait une diminution significative de la phosphorylation sur les résidus sérine pour l’α-Tm 1, la TnT et la MLC-2 et sur les résidus de tyrosine pour l’αB-crystalline ainsi qu’une augmentation significative de la phosphorylation sur les résidus tyrosine pour la MLC-1 et sur les résidus de sérines pour la desmine, confirmant ainsi les résultats obtenus en électrophorèse bidimensionnelle. Afin de compléter l’analyse des modifications post-traductionnelles, nous avons étudié les modifications de O-GlcNAc pour chacune de ces protéines. Nous avons ainsi observé une diminution significative de la O-GlcNAcylation de l’α-Tm 1, de la desmine et l’αB crystalline ainsi qu’une augmentation de la O-GlcNAcylation de la MLC-3 et de la TnT. Par ailleurs, nous avons pu corréler ces modulations de phosphorylation et de O-GlcNAcylation avec des modulations de l’activité des enzymes impliquées dans ces modulations. En effet, par analyse bioinformatique de la séquence de la TnT et par recherche bibliographique nous avons mis en évidence que la protéine kinase C et la protéine phosphatase 2A pourrait être impliquées dans ces modulations de phosphorylation. Nous avons alors mis en évidence une diminution de l’activité de la protéine kinase C epsilon dans le VG des rats IC mais sans variation de l’activité de la protéine phosphatase 2A. Par ailleurs, nous avons mis en évidence une augmentation de l’activité de la O-GlcNAc transférase et une diminution de l’activité de la O-GlcNAcase dans le VG des rats IC. [...] / Despite significant improvements in management of myocardial infarction (MI), left ventricular remodelling (LVR) remains a major complication and a strong predictor of both heart failure (HF) and death after MI. Although several variables, such as MI size, have been identified as risk factors, LVR remains difficult to predict in clinical practice. Better prediction could allow an individualized approach with more intense therapy and follow-up for such high-risk patients. The aim of my work is to identify molecular determinants of LVR to have a better understanding of physiopathological mechanisms of LVR. For that purpose, we studied post-translational modifications of contractile proteins in particular, phosphorylation and O-N-acetylglucosaminylation (O-GlcNAc). Then, we studied particularly troponin T (TnT) for which we could highlight a decrease of phosphorylation of serine 208 in LV and plasma of MI-rats. These results suggest that the level of circulating phosphorylated troponin T could be new biomarker of LVR and may help to predict the development of heart failure after MI. For this study, we worked in collaboration with INSERM unit U644 at Rouen using an experimental model of HF. MI was induced in rat by left coronary ligation and, the control rats undergoing the surgery without ligation. Initially, we performed differential phosphoproteomic study of LV in the late phase of the LVR (2 months post-MI). For this purpose, LV proteins were extracted and separated by two-dimensional electrophoresis. Gels were first stained by Pro-Q®Diamond (specific of phosphorylated proteins) and then by Sypro®Ruby (specific of total proteins). By bioinformatic analysis, we showed that 69 polypeptidic spots were modulated for their phosphorylation levels. We analyzed these spots by mass spectrometry and identified 30 proteins corresponding to 53 spots with modulationof phosphorylation. Among these proteins, we have chosen to study 6 contractile proteins: TnT, alpha-tropomyosin 1 (Tm-α1), desmin, αB-crystallin and myosin light chains 1 and 2 (MLC). For each described proteins, we have validated the modulation of phosphorylation and determined the aminoacid involved in the phosphorylation modulation using immunoprecipitation techniques with specific antibodies against the proteins and phospho-Tyrosine, -Threonine and –Serine antibodies confirming the screening performed by 2D-electrophoresis for the detection of phosphoproteins. We observed a significant decrease of phosphorylation on serine for Tm-α1, TnT and MLC-2 and on tyrosine residues for αB-crystallin as well as a significant increase in phosphorylation on tyrosine for MLC-1 and on serine residues for desmin, thus confirming the results obtained in two-dimensional electrophoresis. In order to complete analysis of the post-translational modifications, we studied the modifications of O-GlcNAc for each one of these proteins. We thus observed a significant decrease in O-GlcNAcylation of Tm-α1, αB-crystallin and desmin as well as an increase in O-GlcNAcylation of the MLC-3 and TnT. In addition, we have correlated these modulations of phosphorylation and O-GlcNAcylation levels with modulations of the activity of enzymes implied in these modulations. Indeed, by bioinformatic analysis of the TnT sequence and literature review, we highlighted that the protein kinase C and the protein phosphatase 2A could be implied in these modulations. We observed a decrease of protein kinase C epsilon isoform expression in the LV of MI- rats without modulation of protein phosphatase 2A activity. In addition, we showed an increase in the activity of O-GlcNAc transferase and a decreaseof O-GlcNAcase activity in LV of MI rats. [...]

M.A. / The study investigated the effects of cardiac arrest and myocardial infarction on long-term memory function. Given that anoxia has more serious neuropsychological ramifications than hypoxia, it was hypothesized that the cardiac arrest group would perform poorer than the myocardial infarction group in visuo-spatial and auditory-verbal recall and recognition memory. When brain insult prevails, affective changes may occur and may reflect the trauma related to the illness and partly to the cognitive dysfunction. Thus it was hypothesized that the Beck Depression Inventory scores would be significantly elevated in the cardiac arrest group. Each group consisted of 15 participants. The mean age for the cardiac arrest group and myocardial infarction group was 59.47 years (SD = 9.24) and 58.87 years (SD = 7.22), respectively. Sex, age, education, hypertension, diabetes mellitus, and smoking were controlled. However, the analysis did not reveal any significant between-group differences. There was no significant difference on the BDI, and both groups were moderately depressed, the cardiac arrest (BDI: mean score = 17.07, SD = 16.97) and myocardial infarction (BDI: mean score = 18.33, SD = 18.35). The researchers acknowledged the potential effects that beta-adrenoceptor antagonists and diuretics, and angiotensin-converting enzyme have on memory and cognitive performance, respectively. However, the analysis did not reveal a significant between-group difference for these variables. The neuropsychological test battery comprised: Rey-Auditory Verbal Learning Test (RAVLT), Rey-Osterreith Complex Figure Test (ROCFT), Wechsler Memory Scale-Revised (WMS-R), Wechsler Adult Intelligence Test (WAIS) Symbol Search and Digit Symbol Substitution Test, Raven’s Standard Progressive Matrices, and the Oral Word Controlled Test (FAS). The memory function of the cardiac arrest group was characterized by deficits in visuo-spatial and auditory-verbal recall and recognition memory. In addition, the retention intervals were not mediating factors. This group was also impaired in visuo-spatial perception, constructional and organizational ability, and psychomotor speed. The impairment that characterized the myocardial infarction group converged on all auditory-verbal attentional tasks, indicating that this group has a selective impairment in auditory-verbal attention. Moreover, both groups exhibited equal levels of impairment in orientation, and uniform performance in executive function and verbal fluency. The memory function after cardiac arrest is characterized by deficits in visuo-spatial and auditory-verbal deficits in recall and recognition memory as well as impairment in visual perception, constructional ability, and psychomotor speed. By contrast, myocardial infarction patients are specifically impaired in auditory-verbal attention.

Myocardial infarction is a prominent medical problem in the world today. Current treatments are limited and do not strive to regenerate the myocardial tissue that is lost post-infarction. Human mesenchymal stem cells (hMSCs) have been shown to improve cardiac function when implanted post-infarction. The effectiveness of stem cell therapy largely depends on the delivery method. Current delivery methods are insufficient due to their low cell engraftment rate and inability to target the endocardium, where most myocardial infarctions occur. Biological microthreads are a promising new local cell delivery method that may improve upon these current limitations. We hypothesize that biological microthreads will increase efficiency of hMSC delivery to the beating rat heart compared to intramyocardial injection. To test our hypothesis we seeded biological microthreads in vitro with 100 ìL of cell suspension (100,000 hMSCs). After one day, an average of 11,806 ± 3,932 hMSCs were counted on the biological microthreads. The biological microthreads were attached to suture needles to allow targeted delivery to the rat heart (in the left ventricular wall). Human mesenchymal stem cells were loaded with quantum dots prior to seeding the biological microthread bundles or delivery to the rat heart via injection. For intramyocardial injection, a cell suspension containing 10,000 hMSCs (35 ìL) was injected into the myocardial wall using a 100 ìL syringe. The delivery efficiency of each method was determined by sectioning the heart into 8 µm thick sections and analyzing three sections every sixty sections (24 µm every 480 µm) for quantum dot loaded hMSCs. These sections were stained with Hoechst dye and quantum dot loaded cells in the heart sections were manually counted. The delivery efficiency of each biological microthread implantation was calculated by dividing the number of counted quantum dot loaded hMSCs in the heart wall by the average number of hMSCs on the biological microthread bundles (normalized to the length that was implanted in the heart wall) after 24 hours. The delivery efficiency of intramyocardial injection was calculated by dividing the number of counted quantum dot loaded hMSCs in the heart wall by 10,000 (the number of cells injected). Biological microthread mediated hMSC delivery had a significantly higher delivery efficiency (66.6 ± 11.1%) compared to intramyocardial injection (11.8 ± 6.25%) after 1 hour (p < 0.05). Biological microthread implantation tracking illustrated that we were able to deliver hMSCs to the myocardium and endocardium of the left ventricular wall for hMSC delivery. This study illustrates that biological microthreads can serve as an efficient means of delivering hMSCs to the infarcted heart. Unlike the currently utilized delivery methods, biological microthreads can target the infarcted layer of the left ventricular wall and maximize hMSC engraftment to that layer.

Resumo: 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... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: 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) / Orientador: Leonardo Antonio Mamede Zornoff / Coorientador: Marcos Ferreira Minicucci / Banca: Beatriz Bojikian Batsubara / Banca: Carlos Eduardo Rochitte / Banca: Katashi Okoshi / Banca: Wilson Nadruz Junior / Doutor

Chui Wai Leung. / Thesis (M.Sc.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (leaves 120-126). / List of tables and figures --- p.1 / Declaration --- p.6 / Acknowledgments --- p.7 / Summary --- p.8 / Chapter Chapter 1: --- Introduction --- p.10 / Chapter 1.1 --- Acute Myocardial Infarction (AMI) / Chapter 1.2 --- Diagnosis of AMI / Chapter 1.2.1 --- Clinical Signs / Chapter 1.2.2 --- Electrocardiogram (ECG) / Chapter 1.2.3 --- Cardiac enzymes / Chapter 1.3 --- "CKMB,a marker of choice" / Chapter 1.4 --- "Troponin-T, another candidate marker" / Chapter 1.5 --- Objectives / Chapter Chapter 2: --- Analytical evaluation of CKMB measurement by the four methods --- p.20 / Chapter 2.1 --- Analytical methods / Chapter 2.1.1 --- Assay for total creatine kinase / Chapter 2.1.2 --- Assay for CKMB / Chapter 2.1.2.1 --- CKMB mass concentration assay / Chapter 2.1.2.2 --- CKMB EEC & immunoinhibition activity assay / Chapter 2.1.2.3 --- CKMB activity concentration assay1 / Chapter 2.1.2.4 --- CKMB activity concentration assay2 / Chapter 2.2 --- Precision / Chapter 2.3 --- Accuracy / Chapter 2.4 --- Linearity / Chapter 2.5 --- Recovery / Chapter 2.6 --- Interference / Chapter 2.6.1 --- Effect of haemolysis / Chapter 2.6.2 --- Effect of turbidity / Chapter 2.6.3 --- Effect of bilirubin / Chapter 2.7 --- Stability / Chapter Chapter 3 : --- Correlation among the four methods of CKMB measurement --- p.61 / Chapter Chapter 4 : --- Establishment of reference ranges for the four methods of CKMB measurement --- p.71 / Chapter Chapter 5: --- Information on the Qualitative Troponin-T Rapid Assay® --- p.80 / Chapter Chapter 6 : --- Clinical Evaluation of CKMB and Troponin-T in detection of AMI --- p.82 / Chapter 6.1 --- Material and Methods / Chapter 6.1.1 --- Subjects / Chapter 6.1.2 --- Specimens / Chapter 6.1.3 --- Criteria for diagnosis / Chapter 6.1.4 --- Analytical methods / Chapter 6.1.5 --- Statistical methods / Chapter 6.2 --- Results / Chapter 6.3 --- Discussion / Chapter Chapter 7 : --- General Discussion --- p.105 / Appendix 1: study protocol sheet --- p.113 / Appendix 2: diagnostic criteria for a definite AMI --- p.115 / Appendix 3: criteria for exclusion of AMI --- p.117 / Appendix 4: enzyme criteria --- p.118 / References --- p.120