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1
Adachi, Yuichiro. "Angiotensin 2 type 2 receptor deficiency exacerbates heart failure and reduces survival after acute myocardial infarction in mice." Kyoto University, 2006. http://hdl.handle.net/2433/144310.
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Putot, Alain. "Approche épidémiologique des infarctus du myocarde de type 2 : Etiologies, caractéristiques, traitements et pronostic." Thesis, Bourgogne Franche-Comté, 2020. http://www.theses.fr/2020UBFCI001.
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Introduction : L’infarctus du myocarde (IDM) de type 2 a été récemment défini par un déséquilibre entre apports et besoins du myocarde en oxygène, en l’absence de processus athérothrombotique. L’objectif de ce travail était d’en décrire les principales étiologies, ainsi que les caractéristiques épidémiologiques, cliniques et pronostiques.Méthode : Les données des patients présentant un IDM de type 2 ont été recueillies à partir de l’observatoire des infarctus de Cote d’Or (RICO). Un travail complémentaire a analysé les données rétrospectives du service des urgences du Centre Hospitalier Universitaire (CHU) de Dijon BourgogneRésultats : Parmi 4436 patients consécutifs hospitalisés aux urgences du CHU pour IDM sur 3 ans, 947 (21%) présentaient un IDM de type 2 (âge médian : 81 ans). Dans l’observatoire RICO, 4572 patients consécutifs dont 862 (19%) IDM de type 2 ont été inclus sur 5 ans (âge médian : 77 ans). La mortalité intra-hospitalière des IDM de type 2 était de 14% parmi les patients des urgences et de 11% pour les patients du RICO. Les pathologies chroniques prédisposant à l’IDM de type 2 les plus fréquemment retrouvés étaient l’anémie sévère et le rétrécissement aortique serré. Une infection aigue, dans deux tiers des cas respiratoire, était retrouvée dans 10% de l’ensemble des IDM de la base RICO, représentant de loin le facteur précipitant le plus fréquent dans la genèse des IDM de type 2. Sur le plan thérapeutique, après ajustements sur scores de propension, la transfusion globulaire était associée à une réduction de la mortalité à un an pour les patients >80 ans avec un nadir d’hémoglobine ≤ 8 g/dL. L’angioplastie après IDM post-infectieux n’était pas associée à un meilleur pronostic qu’un traitement médicamenteux seul (mortalité à un an de 24% vs 19%, p = 0.5).Conclusion :L’IDM de type 2 est une pathologie sous-diagnostiquée, représentant 20% des IDM, et fréquente chez le sujet âgé. Elle est associée à un sur-risque de mortalité par rapport aux IDM de type 1. Les infections aigues, en particulier respiratoires, représentent le facteur déclenchant le plus fréquent. Sur la base de données observationnelles, l’angioplastie coronaire ne semble pas associée à une amélioration du pronosticIntroduction: Type 2 Myocardial infarction (MI)has been recently defined as an imbalance between oxygen supply and demand, in the absence of atherothromthrombosis. This work aimed to describe the main etiolgies as well as epidemiological, clinical and prognostic characteristics.Method: Data from patients with type 2 MI were collected from the RICO cohort (Observatoire des Infarctus de Cote d'Or). In a complementary work, we analyzed the retrospective data of the emergency department of Dijon University Hospital.Results: Among 4,436 consecutive patients hospitalized for MI in Dijon emergency department over 3 years, 947 (21%) had type 2 MI (median age: 81 years). In the RICO cohort, 4,572 consecutive patients, including 862 (19%) type 2 MI were included over 5 years (median age: 77 years). Intra-hospital mortality after type 2 MI was 14% among ED patients and 11% for RICO patients. The most common chronic conditions predisposing to type 2 MDI were severe anemia and severe aortic stenosis. An acute infection, from the respiratory tract for rougly 2/3 of them, was found in 10% of all MI in the RICO database, and was by far the most common precipitating factor in the pathogenesis of type 2 MI. Concerning therapeutics, after adjustments on propensity scores, red blood cell transfusion was associated with a one-year mortality reduction for patients >80 years of age with a hemoglobin nadir ≤ 8 g/dL. In Post-infectious PI, percutaneous coronary intervention was not associated with a better prognosis than drug treatment alone (one-year mortality of 24% vs 19%, p = 0.5).Conclusion:Type 2 MI is an underdiagnosed condition, representing 20% of all MI, and is common in the elderly. It is associated with an over-risk of mortality compared with type 1 MI. Acute infections, particularly from the respiratory tract, are the most common triggering factor. Based on observational data, invasive procedures do not appear to be associated with improved prognosis
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Reed, Grant William. "Associations Between Cardiac Troponin, Mechanism of Myocardial Injury, and Long-Term Mortality After Non-Cardiac Vascular Surgery." Case Western Reserve University School of Graduate Studies / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1491571890479287.
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Grzesiak, Aleksandra [Verfasser]. "Angiotensin II type 2 receptor stimulation : a novel options of therapeutic interference with the renin-angiotensin system in myocardial infarction? / Aleksandra Grzesiak." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2014. http://d-nb.info/1052529879/34.
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Yao, Coffy-Akpolet. "Nouvelles approches épidémiologiques des infarctus du myocarde de type 2 : vers une prise en charge personnalisée." Electronic Thesis or Diss., Bourgogne Franche-Comté, 2023. http://www.theses.fr/2023UBFCI011.
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Introduction : l’infarctus du myocarde (IDM) de type 2, qui résulte d’un déséquilibre entre les apports et les besoins en oxygène du myocarde en l’absence d’événement athéro-thrombotique, est une entité mal connue. L’objectif de ce travail était de préciser certains aspects épidémiologiques et diagnostiques de l’IDM de type 2, notamment la place de la maladie coronaire, et d’évaluer la pertinence clinique et pronostique d’une nouvelle classification des IDM proposée par de LemosMéthodes : A partir de la base de données de l’Observatoire des Infarctus de la Côte d’Or (RICO), nous avons analysé les données des patients hospitalisés pour un IDM entre 2012 et 2017, après adjudication des IDM de type 1, de type 2 et des sous types identifiés selon la nouvelle classification distinguant les IDM de type 2 avec (IDM de type 2A) et sans maladie coronaire sous-jacente (IDM de type 2B). Nous avons également réalisé une revue systématique de la littérature sur la maladie coronaire obstructive (MCO) dans l’IDM de type 2 à partir de la base de données PubMed®. Enfin, nous avons travaillé sur le REgistre des InfArctus de CôTe d’IVoire (REACTIV) hospitalisés pour un IDM entre 2018 et 2022 à l’Institut de cardiologie d’Abidjan, afin d’identifier les spécificités des IDM de type 2 dans cette population Sub-Saharienne.Résultats : Parmi les 4573 patients inclus dans l’observatoire RICO sur une période de 5 ans, 3806 (81,1%) patients et 767 (18,9%) présentaient respectivement un IDM de type 1 et un IDM de type 2 après reclassification. Une coronaropathie obstructive était retrouvée chez 68,6 % des patients atteints d’IDM de type 2. L’IDM de type 2A concernait des patients plus âgés (âge médian 78 ans), avec davantage de comorbidités, et il était associée à un plus mauvais pronostic à 1 an, comparativement aux IDM de type 2B et aux IDM de type 1 de nature athéro-thrombotique (type 1A). Nos données retrouvent un surrisque, d’environ 40%, pour la mortalité toutes causes (RR 1,362; IC95% 1,029-1,802) de l’IDM de type 2A par rapport à l’IDM de type 1A. La revue systématique nous a permis de monter une prévalence particulièrement variable de la MCO dans l’IDM de type 2 (entre 30 et 92%), dépendante des définitions, du mode diagnostique de la coronaropathie et de l’origine des populations étudiées. Chez des patients admis aux urgences, un antécédent de MCO était un facteur prédictif indépendant de présenter un IDM de type 2 par rapport à un IDM de type 1, avec une augmentation de cette probabilité de près de 40%. (RR 1,38; IC95% 1,08-1,77). Enfin, parmi les patients inclus dans le programme REACTIV, 62 (14,1%) ont présenté un IDM de type 2. Comparativement aux IDM de type 1, les IDM de type 2 avaient une tendance à être plus jeunes (54 vs 58 ans, p = 0,09), avec une plus faible fréquence de facteurs de risque cardiovasculaires. Les IDM de type 2 présentaient une MCO moins sévère, avec une atteinte tritronculaire moins fréquente (p < 0,001). Dans cette population sub-saharienne, l'embolie coronaire (24,2 %), l'hypertension sévère ± hypertrophie ventriculaire gauche (22,6 %) et la tachyarythmie (16,1 %) constituaient les principaux facteurs déclenchants.Conclusion : Nos travaux soutiennent l’hypothèse que l’IDM de type 2, souvent considérée comme une pathologie gériatrique, semble en réalité présenter une grande hétérogénéité épidémiologique et physiopathologique. De plus, nous suggérons que l’identification de la maladie coronaire, dont la prévalence est élevée, pourrait permettre d’améliorer la caractérisation et la stratification du risque des IDM de type 2 et ainsi guider le développement d’études interventionnelles pour améliorer leur prise en chargeIntroduction : Type 2 myocardial infarction (MI) resulting from an imbalance between oxygen supply and demand, in the absence of atherothrombosic phenomenom, remains an enigmatic clinical entity. This work aimed to precise type 2 MI epidemiological and prognostic features, especially the key role of coronary artery disease (CAD), and to appraise the clinical and prognostic relevance of a new classification of MI proposed by de Lemos.Method : Using the Observatoire des Infarctus de la Côte d'Or (RICO), we collected data from patients hospitalized for MI, including differentiation between type 1 (T1MI) and type 2 MI (T2MI), after adjudication of type 1 MI and type 2 MI, and sub-groups according to the new classification, with categorization of T2MI into those with (T2AMI) or without (T2BMI) obstructive coronary artery disease (CAD). We also conducted a systematic review of the literature on the role of obstructive CAD in T2MI using the PubMed® database. Finally, we analyzed data from the REgistre des InfArctus de CôTe d'IVoire (REACTIV) at the Abidjan Heart Institute, in order to identify the specific features of type 2 MI in this Sub-Saharan Africa population.Results : Among the 4573 patients included in RICO over a 5-year period, 3806 (81.1%) and 767 (18.9%) had T1MI and T2MI after reclassification, respectively. Obstructive CAD was identified in 68.6% of patients with T2MI. T2AMI affected older patients (median age 78 yo), with more comorbidities, and is associated with poorer outcomes after 1-year follow-up, compared with T2BMI and even T1MI due to atherothrombosis (T1AMI). Our data show a 40% excess all-cause mortality at 1-year (HR 1.362; IC95% 1.029-1.802) in T2AMI versus T1AMI. Based on the systematic review of the literature, we found a wide range of CAD prevalence in type 2 MI (between 30% and 92%), depending on definition criteria, diagnostic tools and populations studied. In patients admitted to the emergency department, history of obstructive CAD was an independent predictor of T2MI versus T1MI, increasing this probability by 40% (OR 1.38; 95%CI 1.08-1.77). Finally, of the MI patients included in REACTIV registry over 4 years, 62 (14.1%) met the definition of T2MI. Patients with T2MI were slightly younger (54 vs. 58 years, p = 0.09) with fewer conventional CV risk factors. Patients with T2MI had less severe CAD, with less 3-vessel CAD (p < 0.001). The main triggering factors for T2MI in this Sub-Saharan population were coronary embolism (24.2%), severe hypertension ± left ventricular hypertrophy (22.6%) and tachyarrhythmia (16.1%).Conclusion : Our work support the hypothesis of epidemiological and pathophysiological heterogeneity of T2MI, despite it is increasingly considered as a geriatric condition. Furthermore, we suggest that the identification of CAD, which is highly prevalent, could improve the characterization and risk stratification of type 2 MI, and help target interventional studies to improve its management and outcomes
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Lauer, Dilyara [Verfasser]. "Prevention of cardiac remodeling after experimental myocardial infarction. Role of the angiotensin II type 2 receptor stimulation and modulation of MMP/TIMP axis / Dilyara Lauer." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2016. http://d-nb.info/1119803527/34.
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Davidson, Melissa Anne. "A Pharmacovigilance Approach for Assessing Cardiovascular, Osteological, and Carcinogenic Risk Associated with Thiazolidinedione Drugs Used in the Treatment of Type 2 Diabetes Mellitus." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/38062.
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Diabetes is a chronic and debilitating disease that affects nearly half a billion people worldwide with the vast majority of diabetics suffering from Type 2 diabetes mellitus (T2DM), a disease characterized by insulin insensitivity that often requires pharmacotherapy to effectively maintain target blood sugar levels. The thiazolidinedione (TZD) class of drugs consists of oral hypoglycaemic agents used alone or in combination with other antidiabetic drugs to treat T2DM. The drugs within this class, which include rosiglitazone and pioglitazone, were originally heralded as providing novel first and second-line treatment of T2DM with glycaemic control and physiological effects comparable to, and in some cases, better than, first-line treatments such as metformin. However, over time they have also been associated with adverse cardiovascular, osteological, and carcinogenic effects in some, but not all clinical trials, observational studies, and meta-analyses. Given the conflicting evidence to date on the safety of TZD drugs, their role in the treatment of T2DM continues to be debated and epidemiological gaps remain. The objectives of this doctoral research are fourfold: 1) to conduct an in-depth review of the epidemiology of TZD pharmacotherapy including pharmacokinetics and modes of action, the results of previous studies investigating health risks and benefits associated with TZD treatment, and new and future uses for this class of drugs; 2) to determine whether diabetic patients treated with TZDs are at increased risk of adverse cardiovascular outcomes; 3) to assess whether TZD pharmacotherapy is associated with an increased risk of bone fractures and whether risks differ depending on fracture site and patient sex; and, 4) to investigate associations between TZD use and risk of bladder cancer. Specific research questions were investigated using nested case-control analyses designed to capture incident users of antidiabetic drugs and electronic health data from Cerner Health Facts®, an electronic medical record database that stores time-stamped patient records from more than 480 contributing hospitals throughout the United States. Findings from this work are reported in a series of manuscripts, including a published review paper. Key findings include: 1) TZD use was associated with an increased risk of incident myocardial infarction and congestive heart failure compared to never use of TZD drugs with a trend towards a potential early treatment effect within the first year of exposure to pioglitazone; 2) TZD use was associated with an increased risk of closed bone fractures among Type 2 diabetics with use of pioglitazone or rosiglitazone associated with an increased risk across multiple fracture sites in women, but only rosiglitazone use in men and only at peripheral fracture sites; 3) use of either pioglitazone or rosiglitazone were associated with an increased risk of incident bladder cancer compared to never users, however, a low number of bladder cancer cases resulted in underpowered analyses; and, 4) insulin use in a hospital setting may replace a patient's normal course of antidiabetic therapy which, when combined with other potential sources of bias in traditional nested case-control studies using hospital-based data, may lead to overestimation or underestimation of adverse health risks associated with non-insulin antidiabetic therapies. Although these findings warrant replication, the results of the research contained within this dissertation suggest that caution should be exercised when prescribing diabetic patients TZD drugs if they have cardiovascular, osteological, or carcinogenic risk factors. Additional pharmacovigilance studies should also continue to strive to better understand the health risks related to TZD therapy, especially as new therapeutic roles for TZDs in the prevention and treatment of some cancers, inflammatory diseases, and other conditions in non-diabetic populations are being explored.
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Wu, Chiung-Jung. "Promoting self-management for patients with type 2 diabetes following a critical cardiac event." Thesis, Queensland University of Technology, 2007. https://eprints.qut.edu.au/16465/1/Chiung-Jung_Wu_Thesis.pdf.
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Type 2 diabetes is a global health problem. Evidence indicates that type 2 diabetes can lead to serious complications, such as a cardiac event, which usually require critical nursing care. Patients with type 2 diabetes and with a history of cardiac disease are at greater risk of a further cardiac event requiring readmission to hospital.
Evidence indicates that improved diabetes management assists patients with type 2 diabetes to manage their condition efficiently, reduces risks of a further cardiac event, and therefore reduces hospitalisations. However, there is limited information found regarding a diabetes management program specifically for patients who have already had cardiac complications. Difficulties in developing patients' skills in managing and modifying their daily lives also present a challenge to coronary care staff. Therefore, there is a real need to develop a special diabetes management program for patients with diabetes who have experienced a critical cardiac event, which will be commenced in the Coronary Care Unit (CCU).
The aim of this research is to gain a greater understanding of the characteristics, secondly to obtain in-depth understanding of needs and experiences of patients with type 2 diabetes hospitalised for a critical cardiac event. A further aim is to develop and pilot test a diabetes management program, specific to the patients with diabetes in the context of the CCU.
The design of this research employed three studies: Study I was an exploratory study, which obtained patients' demographic and disease characteristics from the hospital records of all patients with diabetes admitted to the CCU of one public hospital between 1 January 2000 to 31 December 2003. Study II used a qualitative interpretative approach and aimed to gain an in-depth understanding of the perspectives of patients with type 2 diabetes who have experienced a critical cardiac event in managing their everyday lives with both diabetes and cardiac conditions. Study III included two parts. The first utilised the information from the first two studies and the literature (self-efficacy theory) to develop a diabetes self-management program specifically for patients with diabetes who have had a critical cardiac event. The second part pilot tested the newly-developed diabetes self-management program for patients with diabetes admitted to CCU following a critical cardiac event. The pilot study used a randomised controlled trial research design to evaluate the efficacy of the program.
Study I collected data from one hospital's records retrospectively from 2000 to 2003. The results of Study I showed there were 233 (14.7%) patients admitted to CCU that had diabetes out of the total 1589 CCU admissions during the study period. More than 22% of CCU patients with diabetes were readmitted to hospital within 28 days, compared to 6% of CCU patients without diabetes. Patients with diabetes who had a longer CCU stay were more likely to be readmitted. These results indicate that a significant proportion of a CCU population had type 2 diabetes and is more likely to be readmitted to hospital.
Study II used an interpretive approach comprising open-ended interviews to collect data from patients with type 2 diabetes experiencing a cardiac event who had a CCU admission in 2000-2003. The findings revealed that patients with diabetes who had a critical cardiac event experienced considerable feelings of hopelessness and fatigue. Patients also had concerns in the areas of self-confidence and confidence in health professionals. Patients indicated that greater self-confidence and confidence in health professionals would help their ability to manage their daily lives. Therefore, it is very important that intervention programs for these at-risk patients need to improve patients' confidence levels, and reduce their feelings of hopelessness and fatigue.
The information gathered from Study I and Study II provided important insight into the development of an effective diabetes self-management specifically designed for patients with type 2 diabetes following a critical cardiac event, which is presented in Study III in this thesis. Study III also provided a preliminary evaluation of the newly developed program. The evaluation used a randomised controlled trial research design for the new program and the current educational program provided in the CCU. The results of the program indicate the feasibility of commencing the new diabetes self-management program in the CCU, and to be continued in wards or at home. The results also showed significant improvements in patients' knowledge in the experimental group, but not in other outcome variables (self-efficacy, vitality and mental health levels). However, as a small sample size was used in this pilot study, a larger study is needed to ensure adequate testing of the intervention. Future research is also recommended to incorporate the new diabetes self-management program into the current cardiac education program. Staff's further professional development in providing such a program also needs to be examined. Improvements in quality of care, and patients' quality of life are expected in the future.
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Wu, Chiung-Jung. "Promoting self-management for patients with type 2 diabetes following a critical cardiac event." Queensland University of Technology, 2007. http://eprints.qut.edu.au/16465/.
Full textAbstract:
Type 2 diabetes is a global health problem. Evidence indicates that type 2 diabetes can lead to serious complications, such as a cardiac event, which usually require critical nursing care. Patients with type 2 diabetes and with a history of cardiac disease are at greater risk of a further cardiac event requiring readmission to hospital.
Evidence indicates that improved diabetes management assists patients with type 2 diabetes to manage their condition efficiently, reduces risks of a further cardiac event, and therefore reduces hospitalisations. However, there is limited information found regarding a diabetes management program specifically for patients who have already had cardiac complications. Difficulties in developing patients' skills in managing and modifying their daily lives also present a challenge to coronary care staff. Therefore, there is a real need to develop a special diabetes management program for patients with diabetes who have experienced a critical cardiac event, which will be commenced in the Coronary Care Unit (CCU).
The aim of this research is to gain a greater understanding of the characteristics, secondly to obtain in-depth understanding of needs and experiences of patients with type 2 diabetes hospitalised for a critical cardiac event. A further aim is to develop and pilot test a diabetes management program, specific to the patients with diabetes in the context of the CCU.
The design of this research employed three studies: Study I was an exploratory study, which obtained patients' demographic and disease characteristics from the hospital records of all patients with diabetes admitted to the CCU of one public hospital between 1 January 2000 to 31 December 2003. Study II used a qualitative interpretative approach and aimed to gain an in-depth understanding of the perspectives of patients with type 2 diabetes who have experienced a critical cardiac event in managing their everyday lives with both diabetes and cardiac conditions. Study III included two parts. The first utilised the information from the first two studies and the literature (self-efficacy theory) to develop a diabetes self-management program specifically for patients with diabetes who have had a critical cardiac event. The second part pilot tested the newly-developed diabetes self-management program for patients with diabetes admitted to CCU following a critical cardiac event. The pilot study used a randomised controlled trial research design to evaluate the efficacy of the program.
Study I collected data from one hospital's records retrospectively from 2000 to 2003. The results of Study I showed there were 233 (14.7%) patients admitted to CCU that had diabetes out of the total 1589 CCU admissions during the study period. More than 22% of CCU patients with diabetes were readmitted to hospital within 28 days, compared to 6% of CCU patients without diabetes. Patients with diabetes who had a longer CCU stay were more likely to be readmitted. These results indicate that a significant proportion of a CCU population had type 2 diabetes and is more likely to be readmitted to hospital.
Study II used an interpretive approach comprising open-ended interviews to collect data from patients with type 2 diabetes experiencing a cardiac event who had a CCU admission in 2000-2003. The findings revealed that patients with diabetes who had a critical cardiac event experienced considerable feelings of hopelessness and fatigue. Patients also had concerns in the areas of self-confidence and confidence in health professionals. Patients indicated that greater self-confidence and confidence in health professionals would help their ability to manage their daily lives. Therefore, it is very important that intervention programs for these at-risk patients need to improve patients' confidence levels, and reduce their feelings of hopelessness and fatigue.
The information gathered from Study I and Study II provided important insight into the development of an effective diabetes self-management specifically designed for patients with type 2 diabetes following a critical cardiac event, which is presented in Study III in this thesis. Study III also provided a preliminary evaluation of the newly developed program. The evaluation used a randomised controlled trial research design for the new program and the current educational program provided in the CCU. The results of the program indicate the feasibility of commencing the new diabetes self-management program in the CCU, and to be continued in wards or at home. The results also showed significant improvements in patients' knowledge in the experimental group, but not in other outcome variables (self-efficacy, vitality and mental health levels). However, as a small sample size was used in this pilot study, a larger study is needed to ensure adequate testing of the intervention. Future research is also recommended to incorporate the new diabetes self-management program into the current cardiac education program. Staff's further professional development in providing such a program also needs to be examined. Improvements in quality of care, and patients' quality of life are expected in the future.
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Curato, Caterina. "Identification of a non-cytotoxic and IL-10- producing CD8+AT2R+ T lymphocyte population in response to ischemic heart injury." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2011. http://dx.doi.org/10.18452/16362.
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Neuere Untersuchungen legen eine kardioprotektive Rolle für den Angiotensin AT2-Rezeptor nahe, welcher die Postinfarkt-Entzündungsreaktion vermindert, wobei der zelluläre Mechanismus noch wenig verstanden ist. Das Ziel dieser Arbeit war es deshalb, die potentielle Rolle des AT2-Rezeptors in der zellulären Immunantwort auf ischemische Herzverletzungen zu ergründen. Sieben Tage nach myokardialem Infarkt in Ratten wurde der AT2-Rezeptor mittels Immunfluoreszenzfärbung von Gewebeschnitten in einer CD8 T-Zellfraktion detektiert, die das Peri-Infarkt-Myokard infiltiert hatte. Wir haben eine Methode entwickelt, die es mittels kombinierter MACS und FACS Technilogie ermöglicht, CD8+AT2R+ T-Zellen aus dem Myokard zu isolieren und zu analysieren. Im Gegensatz zu den CD8+AT2R- T-Zellen, die in Kultur sowohl auf adulte als auch auf fötale Kardiomyozyten stark zytotoxisch wirkten, zeigten die CD8+AT2R+ T-Zellen keinerlei Zytotoxizität. Die CD8+AT2R+ T-Zellen zeigten eine erhöhte Expression von IL-10 und eine geringere mRNA Expression von IL-2 und IFN-gamma im Vergleich zu CD8+AT2R-T-Zellen. Weiterhin konnten wir zeigen, dass in vitro Stimulation des AT2-Rezeptors zur Hochregulation der IL-10-Expression von CD8+ T-Zellen führt. Entsprechend führt die in vivo Aktivierung des AT2-Rezeptors zur Vergrößerung der CD8+AT2R+ T-Zellpopulation und erhöhter IL-10-Produktion im ischemischen Myokard. Diese CD8+AT2R+ T-Zellen konnten auch in humanem periphärem Blut detektiert werden. Wir haben eine CD8+AT2+T-Zellpopulation definiert, welche sich während ischemischer Herzverletzung vergrößert und das Kardiomyocytenüberleben mittels kardioprotektivem IL-10 aufrechterhält. Somit konnten wir einen neuartigen AT2-Rezeptorvermittelten zellulären Mechanismus aufdecken, welcher die adaptive Immunantwort im Herzen moduliert.One important aspect of cardiac remodeling after myocardial infarction is the activation of an immune response, which removes death cardiomyocytes and initiates scar formation. On the other hand, activation and infiltration of immunocompetent cells are responsible for augmenting damage in non-infarcted areas. Emerging evidence suggests a cardioprotective role of the angiotensin AT2R by attenuating this post-infarct inflammatory reaction, albeit the underlying cellular mechanisms are not well understood. We aimed here at elucidating a potential role of the cardiac angiotensin AT2R in regulating the cellular immune response to ischemic heart injury. Seven days after myocardial infarction in rats, immunofluorescence staining of tissue sections showed that AT2R was detected in a fraction of CD8+ T cells infiltrating the peri-infarct myocardium. We developed a method that allowed the isolation and characterization of CD8+AT2R+ T cells infiltrating the myocardium via combined MACS and FACS technology. While the CD8+AT2R- T cells exhibited potent cytotoxicity to both adult and fetal cardiomyocytes in vitro, the CD8+AT2R+ T cells were non-cytotoxic to these cardiomyocytes. The CD8+AT2R+ T cells were characterized by upregulated IL-10 and downregulated IL-2 and INF-gamma gene expression when compared to CD8+AT2R- T cells. We further showed that IL-10 gene expression was enhanced in CD8+ T cells upon in vitro AT2R stimulation. In addition, in vivo AT2R activation leads to an increment of the CD8+AT2R+ T cells and IL-10 production in the ischemic myocardium. Moreover, the CD8+AT2R+ T cell population was also detected in human peripheral blood. We have defined a CD8+ T cell population that expresses AT2R and increases during ischemic heart injury. This population sustains cardiomyocyte viability by providing cardioprotective IL-1 via a novel AT2R-mediated cellular mechanism for modulating adaptive immune response in the heart.
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Jacquin, Laurent. "Déséquilibre d’oxygénation et lésions myocardiques aiguës : approche clinique en service d’accueil des urgences." Thesis, Lyon, 2021. https://n2t.net/ark:/47881/m6736qrr.
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Dans ce travail de thèse, nous nous sommes intéressés en première partie aux critères de déséquilibre d’oxygénation impliqués dans la survenue d’un infarctus de type 2. Nous avons exploré chez 610 patients l’association entre les paramètres de ces critères et la survenue de lésions myocardiques aiguës, et d’infarctus de type 2, ainsi que la relation entre ces paramètres et l’extension de l’atteinte du myocarde. Nos résultats ne montraient pas de lien entre l’amplitude du déséquilibre d’oxygénation et la survenue de lésions myocardiques aiguës. Il n’y avait également pas de corrélation avec l’importance de ces lésions. Nous n’avons donc pas pu définir de seuils restrictifs stricts considérés comme facteur de stress myocardique significatif. Dans la deuxième partie, nous avons comparé le devenir à court terme et à distance des patients admis avec une condition de déséquilibre d’oxygénation en fonction de la présence d’une lésion myocardique, ou d’un infarctus de type 2, et évaluer l’association de ces entités pathologiques avec la mortalité et les évènements cardiovasculaires. Dans cette population de 824 patients, la survenue de lésions myocardiques aiguës non-ischémiques ou d’infarctus de type 2 conduisait à une mortalité hospitalière élevée à plus de 20% et y était significativement associée après ajustement sur les caractéristiques des patients. A plus long terme chez les survivants, le devenir était dépendant des comorbidités sans implication de la survenue de ces lésions myocardiques initiales, avec des taux de mortalité de 27 à 35 % et d’évènements cardiovasculaires de 23 à 40%. Nous avons proposé de confronter ces résultats dans une autre étude, menée prospectivement, avec un suivi standardisé à 6 mois des patients admis en déséquilibre d’oxygénation, dont nous détaillons la méthodologie. Cette cohorte est constituée de 670 patients dont l’analyse des données est en cours. Enfin, dans une troisième partie, nous nous sommes focalisés sur les 675 personnes âgées, qui représente plus de 80% de notre cohorte, pour déterminer les facteurs associés à la survenue de ces lésions myocardiques et infarctus de type 2 en fonction des classes d’âge. Nous avons retrouvé des profils de patients très dépendants de ces classes, liés aux évolutions épidémiologiques du vieillissement. L’individualisation des infarctus de type 2 au sein des lésions myocardiques aiguës n’était cependant pas évidente, de même que l’impact sur la mortalité qui reposait essentiellement sur le poids des comorbiditésIn the first part, we were interested in the criteria of oxygen supply/demand imbalance involved in the occurrence of a type 2 infarction. We explored in 610 patients the association between the parameters of these criteria and the occurrence of acute myocardial injury and type 2 infarction, as well as the correlation between these parameters and the extent of myocardial injury. Our results did not show any association between the importance of oxygen mismatch and the occurrence of acute myocardial injury. There was also no correlation with the magnitude of such injury. Therefore, we could not define strict restrictive thresholds that could be considered a significant myocardial stressor. In the second part, we compared the short-term and the long-term outcomes of patients admitted with an oxygen supply/demand imbalance condition according to the presence of myocardial injury or type 2 infarction and assessed the association of these pathological entities with mortality and major cardiovascular events. In this population of 824 patients, the occurrence of myocardial injury or type 2 infarction led to high in-hospital mortality of more than 20% and was significantly associated with it after adjustment for patient characteristics. In the follow-up of survivors, the outcome was dependent on comorbidities without the involvement of the occurrence of these initial myocardial injuries, with mortality rates of 27 to 35% and major cardiovascular events of 23 to 40%. We proposed to compare these results in another study, conducted prospectively, with a standardized 6-month follow-up of patients admitted for oxygenation failure, the methods of which are detailed here. This cohort consists of 670 patients whose data are currently being analyzed. Finally, in the third part, we focused on the 675 elderly patients, who represent more than 80% of our cohort, to determine the factors associated with the occurrence of these myocardial injuries and type 2 infarction according to age classes. We found very dependent patient profiles in these classes, linked to the epidemiological changes of aging. However, the individualization of type 2 myocardial infarction within acute myocardial lesions was not obvious, nor was the impact on mortality, which was essentially based on the burden of comorbidities
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Herrera, Comoglio Nelly. "Évenements cardiovasculaires majeurs et mortalité en patients traités avec hypoglycémiants non insuliniques." Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0355.
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Le diabète mellitus Type 2 (DMT2) est une maladie chronique et progressive causée par multiples facteurs. Plus de 422 millions de personnes dans le monde ont du diabète; la maladie a un profond impact social et économique. La maladie cardiovasculaire est la cause principale de la morbidité et la mortalité chez les patients diabétiques, qui ont des taux de mortalité plus élevées que la population non-diabétique. La définition de la DMT2 est basée sur ses manifestations métaboliques – surtout celles de glucose sanguin – qui servent comme marqueurs du contrôle et de l’évolution de la maladie. Cependant, tandis qu’on reconnaît l’effet du contrôle de la glucose sanguin sur les complications microvasculaires, son impact sur les complications macrovasculaires ne sont pas clairs. Depuis 2008, les nouveaux agents hypoglycémiants doivent démontrer leur sécurité cardiovasculaire, soit à travers d’une meta-analyse ou d’essais cliniques évaluant les résultat cliniques cardiovasculaires; quelques nouveaux agents ont montré une réduction des effets cliniques (comme infarctus du myocarde et accident cérébrovasculaire) et de la mortalité. Toutefois, les populations qui faisaient partie de ces essais cliniques a grande échelle ont différences avec la population générale; donc, les résultats de ces essais ne sont pas complètement généralisables. Tandis que les essais cliniques randomisés sont toujours considérés le “goldstandard” pour la génération de l’évidence scientifique, les études observationnelles qui sont fait à partir de grande bases de données utilisés pour d’autre propos, dites “secondaires”, sont de plus en plus utilisées pour la génération de l’évidence scientifique complémentaire ou confirmatoire de celle provenant des essais cliniques, surtout quand ces essais ne sont pas disponibles ou sont impraticables. Ce travail montre les résultats d’une étude observationnelle de cohortes, basée sur la population enregistrée en SIDIAP, une large base de données des médecins généraux de Catalogne, qui recueille les registres de plus de 5,5 millions de personnes. Les événements cliniques cardiovasculaires et la mortalité ont été évalués dans la population générale, non-sélectionnée, traitée avec des agents hypoglycémiants non-insuliniques. On attend que les résultats de cette investigation soient utiles pour la prise de décisions, tant au niveau des cliniciens comme au niveau de la santé publiqueType 2 diabetes mellitus (T2DM) is a multifactorial, chronic, progressive disease, affecting more than 422 million people over the world, and having a significant societal and economic impact. Cardiovascular disease is the leading cause of morbidity and mortality in T2DM patients, who have higher rates of mortality than the non-diabetic population. T2DM is defined by its metabolic -mainly glucose-related- manifestations which serve as markers for controlling the evolution of disease. However, while the effect of control serum glucose levels on microvascular complications is acknowledged, its impact on macrovascular complications remains uncertain. Since 2008, new blood glucose-lowering agents have to demonstrate cardiovascular safety, and some have shown to reduce cardiovascular outcomes and mortality. However, the populations included in these large cardiovascular outcome trials differ from the general population, making results no fully generalisable. While randomised controlled trials are the gold standard for generating scientific evidence, observational studies conducted with secondary data of Electronic medical records (EMRs) are increasingly used as a source of complementary or confirmatory evidence, especially when RCTs are not feasible or unavailable. This work report an observational, population-based cohort study conducted in SIDIAP, a large Catalan general practitioners database that contains health data of 5,5 million people. We assessed cardiovascular outcomes and mortality in general, unselected T2DM population treated with non-insulin blood-glucose-lowering agents. The results are expected to be useful both for clinical and public health decision-making
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Cediel, Calderón Germán Eduardo. "Papel de la troponina i como biomarcador pronóstico en pacientes atendidos en los servicios de urgencias sin diagnóstico de síndrome coronario agudo." Doctoral thesis, Universitat Rovira i Virgili, 2017. http://hdl.handle.net/10803/435687.
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En els últims anys, l'ús generalitzat de la troponina en els serveis d'urgències, ha permès la seva detecció en pacients amb diagnòstics clínics diferents a la síndrome coronària aguda (SCA).
L'objectiu d'aquesta tesi va ser establir el valor pronòstic d'una troponina I (cTnI) elevada en el seguiment dels pacients atesos en un servei d'urgències i que no són diagnosticats de SCA, estudiant també, el seu valor pronòstic en els pacients donats d'alta directament des d´urgències. També ens plantegem identificar aquells pacients amb diagnòstic d'infart de miocardi (IM) tipus 2 i injúria miocàrdica no isquèmica i comparar la seva mortalitat i esdeveniments cardiovasculars adversos en el seguiment.
Per respondre a aquests objectius es va realitzar un estudi de cohorts observacional i retrospectiu en el qual es van incloure pacients atesos al servei d'urgències de l'Hospital Universitari Joan XXIII als que es va sol·licitar almenys una determinació de cTnI. Es van identificar les variables demogràfiques, clíniques i analítiques de l'episodi agut, així com les troballes electrocardiogràfiques i les principals exploracions cardiològiques realitzades.
Hem observat que els pacients amb troponina I elevada no diagnosticats de SCA van tenir pitjor supervivència que els pacients amb SCA i els pacients amb cTnI negativa. A més, la cTnI constitueix un marcador independent associat a mortalitat en el seguiment dels pacients que són donats d'alta directament des d´urgències. Finalment, una alta proporció de pacients atesos en urgències amb cTnI positiva compleixen criteris diagnòstics d'IM tipus 2. Els pacients amb diagnòstic d'IM tipus 2 i injúria miocàrdica no isquèmica es caracteritzen per tenir un perfil clínic similar, una elevada taxa de mortalitat i menor proporció de reingrés per SCA en comparació als pacients amb diagnòstic d'IM tipus 1.En los últimos años, el uso generalizado de la troponina en los servicios de urgencias (SU), ha permitido su detección en pacientes con diagnósticos clínicos diferentes al síndrome coronario agudo (SCA). El objetivo de esta tesis fue establecer el valor pronóstico de una troponina I (cTnI) elevada en el seguimiento de los pacientes atendidos en un SU y que no son diagnosticados de SCA, estudiando a su vez, su valor pronóstico en los pacientes dados de alta directamente desde urgencias. También nos planteamos identificar a aquellos pacientes con diagnóstico de infarto de miocardio (IM) tipo 2 e injuria miocárdica no isquémica y comparar su mortalidad y eventos cardiovasculares adversos en el seguimiento. Para responder a estos objetivos se realizó un estudio de cohortes observacional y retrospectivo en el que se incluyeron pacientes atendidos en el SU del Hospital Universitario Joan XXIII a quienes se solicitó al menos una determinación de cTnI. Se identificaron las variables demográficas, clínicas y analíticas del episodio agudo, así como los hallazgos electrocardiográficos y las principales exploraciones cardiológicas realizadas. Hemos observado que los pacientes con troponina I elevada no diagnosticados de SCA tuvieron peor supervivencia que los pacientes con SCA y los pacientes con cTnI negativa. Además, la cTnI constituye un marcador independiente asociado a mortalidad en el seguimiento de los pacientes que son dados de alta directamente desde urgencias. Finalmente, una alta proporción de pacientes atendidos en los SU con cTnI positiva cumplen criterios diagnósticos de IM tipo 2. Los pacientes con diagnostico de IM tipo 2 e injuria miocárdica no isquémica se caracterizan por tener un perfil clínico similar, una elevada tasa de mortalidad y menor proporción de reingreso por SCA en comparación a los pacientes con diagnóstico de IM tipo 1.
Recently, the widespread use of troponin in emergency services has allowed its detection in patients who are not diagnosed with acute coronary syndrome (ACS). The aim of this thesis was to establish the prognostic value of an elevated troponin I (cTnI) in follow-up of patients admitted to the emergency department and without ACS, also studying, its prognostic value in patients discharged directly from the emergency department. We also aimed to identify patients with diagnosis of type 2 myocardial infarction and non-ischaemic myocardial injury and to compare their mortality and cardiovascular events at follow-up. In order to respond to these objectives, an observational and retrospective cohort study was carried out, including all patients admitted at the emergency department in the Hospital Universitario Joan XXIII, and who underwent at least one cTnI determination. We identified the demographic, clinical and analytical variables of the acute episode, as well as the electrocardiographic findings and the main cardiological explorations performed. We found that patients with high troponin levels and without ACS had higher rates of mortality than patients with ACS and patients with negative troponin. In addition, cTnI is an independent predictor associated with mortality in follow-up of patients discharged directly from the emergency department. Finally, a high percentage of patients admitted in the emergency department with high levels of cTnI meet diagnostic criteria for type 2 IM. Patients with a final diagnosis of type 2 myocardial infarction and non-ischemic myocardial injury have a comparable clinical profile, higher rates of mortality and lower readmission rates for ACS compared with patients with type 1 myocardial infarction.
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McSweeney, Sara Jane. "11β-hydroxysteroid dehydrogenase type 1 : a new therapeutic target post-myocardial infarction?" Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/4833.
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Glucocorticoids can reduce infarct size when given immediately after myocardial infarction (MI) but are detrimental when administration is continued into the post-infarct healing phase. A number of experimental studies have shown that reduction of infarct expansion by enhancing blood supply to the infarct border reduces remodelling and improves heart function post-MI. Previous experiments from this laboratory have shown that mice unable to locally regenerate corticosterone due to deficiency in 11β-hydroxysteroid dehydrogenase type 1 (11HSD1) have an enhanced angiogenic response during myocardial infarct healing that is associated with improved cardiac function. We hypothesized that the enhanced angiogenic response in 11HSD1 knock out (-/-) mice would be preceded by augmented inflammation. Moreover this would be associated with improved cardiac function. This thesis aimed firstly to establish that murine cardiac phenotype was not influenced by 11HSD1 deficiency. 11HSD1-/- and C57Bl6 control mice had comparable cardiac structure and function. 11HSD1 expression was localised to fibroblasts and vascular smooth muscle cells in the myocardium. The second aim of this thesis was to characterise the healing response after MI in 11HSD1-/- mice compared to C57Bl6 mice. Neutrophil infiltration peaked 2 days after MI and was significantly enhanced in the 11HSD1-/- mice relative to C57Bl6 mice, despite comparable infarct size in both groups. This was followed by increased macrophage accumulation in the infarct border. Furthermore, in the 11HSD1-/- mice a greater proportion of macrophages were of the alternatively activated phenotype. Left ventricular expression of pro-angiogenic IL-8, but not VEGF, was increased. Cellular proliferation and vessel density at 7 days were greater in 11HSD1-/- compared to C57Bl6 hearts. This was associated with improved cardiac function 7 days post-MI. The third aim of this thesis was to determine whether the enhancement in vessel density and cardiac function was maintained beyond the initial wound healing phase. 11HSD1-/- mice retained the increased vessel density compared to C57Bl6 mice and these vessels were smooth muscle coated suggesting vessel maturation. This was associated with sustained improvement in cardiac function and modification of the scar characteristics. The final aim of this thesis was to establish whether the effect of the knock out could be recapitulated by administration of a small molecule inhibitor of 11HSD1 after MI. Oral administration of the 11HSD1 inhibitor had no effect on inflammation, angiogenesis and heart function as determined at 7 days post-MI relative to vehicle treated animals. In conclusion, the data confirm the enhancement in vessel density and cardiac function in 11HSD1-/- mice and demonstrate that this was preceded by enhanced inflammation. This was not due to an underlying cardiac phenotype or modification of the infarct size. Increased infiltration of alternatively activated macrophages may have been the source of pro-angiogenic factor, IL-8, which was also increased at the time of angiogenesis. Importantly the enhanced vessel density was retained 4 weeks after MI, these vessels were mature suggesting longevity and the improvement in cardiac function was retained. While pharmacological inhibition did not recapitulate the effect of the knock out this may have been due to route of administration. The data provides compelling evidence that further development and use of small molecule inhibitors of 11HSD1 may be of benefit post-MI.
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Oranzie, Marlon. "Electrochemical Aptasensing of B-Type Natriuretic Peptide-A Biomarker for Myocardial Infarction." University of the Western Cape, 2019. http://hdl.handle.net/11394/7707.
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>Magister Scientiae - MScinfarction (MI) affects many parts of the western world and in South Africa alone it is estimated that MI is responsible for 1 in 6 deaths (17.3%). Traditional diagnostic methods for MI include an electrocardiograms and blood tests. The problem with these diagnostic methods are that they are time consuming, require large sample volumes, expensive equipment and complicated machinery. To achieve early detection of MI the discovery of specific, sensitive and reliable biomarkers are required. Brain natriuretic peptide (BNP) has been identified as a reliable biomarker for MI due to the fact that it has a defined cutoff of 100 pg/ml and it is not susceptible to patient‘s age which could make early detection of BNP complicated. Early detection methods for BNP has been based on immunoradiometric assays but problems associated with immunoradiometric assays are that there is a restricted availability of antigens and incubation of the labeled antibody could take up to two weeks which affects the patients waiting time on results. Electrochemical biosensors are emerging as early detection method for MI because they can be designed to be sensitive, specific to BNP at a low cost. This research study reported for the first the successful fabrication and implementation of highly sensitive mercaptosuccinic acid capped nickel selenide quantum dots (MSA-NiSe2 QDs) aptasensor for the detection of BNP. The poly-dispersed MSA-NiSe2 QDs were synthesized via an inexpensive, simple and reproducible aqueous microwave assisted irradiation method. The prepared MSA-NiSe2 QDs were characterized by Ultraviolet spectroscopy (UV-Vis), X-ray Diffraction (XRD), Fourier Transform Infrared spectroscopy (FTIR), High Resolution Transmission/Scanning Electron Microscopy (HR TEM/SEM) and Small Angle X-ray Scattering (SAXSpace). The electrochemical properties of the MSA-NiSe2 QDs were investigated by Cylic Voltammetry (CV) and Electrochemical Impedance Spectroscopy (EIS). HR-TEM revealed the formation of small sized MSA-NiSe2 QDs about 4 nm in diameter which was complemented by SAXSpace. UV-Vis studies showed absorption peaks in the ultraviolet region (100-400 nm) confirming the small size of these QDs as well confirming the direct and indirect bandgap of the QDs. XRD confirmed that the QDs are crystalline and belong to the bulk cubic MSA-NiSe2 QDs phase. FTIR studies confirmed the successful capping of MSA on the QDs due to the disappearance of the thiol peak at 2652 cm-1. Electrochemical studies revealed that the MSA-NiSe2 QDs showed good electrochemical properties on screen printed carbon electrodes (SPCE) which allowed them to be used as a mediating platform between the aptamer and SPCE. The successful detection of BNP was achieved by an incubation process between the aptamer drop coated on the MSA-NiSe2 QDs/SPCE surface overnight. The response of the MSA-NiSe2 QDs based aptasensor towards different concentrations of BNP was studied by differential pulse voltammetry (DPV). DPV showed a good linearly with correlation coefficient of R2 = 0.98. DPV also showed a high sensitivity (0.4513 μA/ pg/mL) towards detecting BNP with a detection limit of 11.93 pg/ml. The value of 11.93 pg/ml falls within the negative predictive value range of 10-100 pg/ml for early-stage diagnosis of BNP.
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Gianelli, Dorothy M. "Comparison study between Type A and Type B individuals' compliance to cardiac rehabilitation following myocardial infarction /." Staten Island, N.Y. : [s.n.], 1987. http://library.wagner.edu/theses/nursing/1987/thesis_nur_1987_giane_compa.pdf.
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Chan, Cangel Pui Yee. "A superior early myocardial infarction marker : human heart-type fatty acid-binding protein /." View Abstract or Full-Text, 2002. http://library.ust.hk/cgi/db/thesis.pl?CHEM%202002%20CHAN.
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Thesis (Ph. D.)--Hong Kong University of Science and Technology, 2002.Includes bibliographical references (leaves 139-166). Also available in electronic version. Access restricted to campus users.
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Groves, Robert W. "A study of the effect of cotreatment of taprostene (CG 4203), a novel stabilized prostacyclin analogue, with saruplase, a gene technologically produced unglycosylated single chain urokinase-type plasminogen activator (r-scuPA), in thrombolysis in vivo." Thesis, University of Bath, 1990. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.278267.
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Luther, Daniel J. "The role of type VI collagen in cardiac remodeling following myocardial infarction in mice." Thesis, Kent State University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3618869.
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Cardiac remodeling is a dynamic process largely propagated by cardiac fibroblasts (CFs), the critical mediators of wound repair. Following myocardial infarction (MI), this process is accelerated resulting in aberrant structural changes to the heart. Investigation into the fibrotic responses of the heart to injury have focused on collagens type I and III however, we have uncovered a novel role for type VI collagen (Col6). Here, we report the effects of the deletion of Col6 from the myocardium during post-MI wound repair and demonstrate that Col6-/- mice are resistant to ischemic injury resulting in reductions in infarct size and preserved cardiac function. To investigate potential mechanisms responsible for the cardioprotection in Col6-/- mice, we used histological approaches to assess the cardiac ECM for structural changes that may alter cardiac wound repair. Our results suggest looser formed collagen fibers and an abundance of type III collagen in the post-MI hearts of Col6-/- mice, in contrast to the abundance of type I collagen observed in WT post-MI mice. Additionally, we hypothesized that altered mitochondrial structure and function in the hearts of Col6 -/- mice also presents a potential mechanism leading to protection from ischemic injury. To test this, we used electron microscopy (EM) and molecular approaches to assess mitochondria of Col6-/- post-MI mice. EMs of Col6-/- uninjured hearts illustrate normal mitochondrial morphology however, at 3 days post-MI Col6-/- mice demonstrate increased mitochondrial fusion, in contrast to increased mitochondrial swelling and fission observed in WT mice. By 14 days, Col6-/- mitochondria appear normal while WT post-MI mice have disrupted mitochondria. Western blot indicated differences in mitochondrial fusion/fission protein flux between groups at 24 hrs. post-MI. Oxygen consumption of isolated mitochondria from Col6-/- sham hearts demonstrate a reduced mitochondrial respiratory control index (RCI) compared to WT controls. Following MI the RCI of Col6-/- mice did not significantly decline, as was observed in WT post-MI mice. Together, these data indicate that Col6-/- mice are protected from ischemic injury leading to improved cardiac remodeling and function following MI, and differences in ECM structure and mitochondrial function are possible mechanism(s) underlying the unexpected cardioprotection observe in Col6 -/- mice.
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Luther, Daniel J. "The Role of Type VI Collagen In Cardiac Remodeling Following Myocardial Infarction In Mice." Kent State University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=kent1376067347.
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Bandyopadhyay, Somnath. "Changes in the mouse left ventricular transcriptome after myocardial infarction." Laramie, Wyo. : [University of Wyoming], 2006. http://proquest.umi.com/pqdweb?did=1212778701&sid=1&Fmt=2&clientId=18949&RQT=309&VName=PQD.
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Keele, Jacque Anne. "Regulation of arginine metabolism following acute myocardial infarction in mice." Laramie, Wyo. : University of Wyoming, 2008. http://proquest.umi.com/pqdweb?did=1707917171&sid=1&Fmt=2&clientId=18949&RQT=309&VName=PQD.
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Miwa, Senri. "Spaciotemporal alteration of 8-hydroxy-2'-deoxyguanosine levels in cardiomyocytes after myocardial infarction in rats." Kyoto University, 2002. http://hdl.handle.net/2433/149330.
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Stevens, Victoria E. "Personality type and ways of coping : a study of female spouses of post myocardial infarction patients /." Access Digital Full Text version, 1992. http://pocketknowledge.tc.columbia.edu/home.php/bybib/11228313.
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Thesis (Ed.D.)--Teachers College, Columbia University, 1992.Includes tables. Typescript; issued also on microfilm. Sponsor: Marilyn Rawnsley. Dissertation Committee: John P. Allegrante. Includes bibliographical references (leaves 135-141).
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Morrice, K. W. "An investigation into the potential utility of Intermedin (adrenomedullin-2) as a biomarker of myocardial ischaemia or infarction." Thesis, Queen's University Belfast, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.580099.
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Introduction: Elevated blood levels of Cardiac Troponin (cTnT) are the gold standard for diagnosis of acute coronary syndrome (ACS). However cTnT is not detectable for 3-4 hours after symptom onset; an early marker of myocardial ischaemia is therefore desirable. The peptide Calcitonin Gene-Related Peptide (CGRP) is released from nerve endings during myocardial ischaemia and has cardioprotective effects. Intermedin (IMD), from the same family, is elevated in myocardial infarction and oxidative stress in animal studies. Methods: I enrolled 81 patients with chest pain, suspected to have acute coronary syndrome to a chest pain study (1). Samples were taken on admission, at 12hours after pain, the next day and the following day. Samples were analysed for intermedin, & CGRP (radioimmunoassay) and High-Sensitivity troponin (HsTnT). Study 2 assessed 30 patients undergoing Percutaneous Coronary intervention (PCI) with 6 controls. Samples taken, pre, 1,5, 10,30, 120 or 240 minutes post balloon inflation and next day. Results: Study 1- Intermedin showed a non-significant trend towards elevation in ACS patients. In those patients who were (cTnT) negative «0.03ng/ml) on presentation, IMD & CGRP were significantly elevated. CGRP was significantly elevated at 12 hours after ACS onset and appeared to remain elevated for 48 hours. HsTnT identified more ACS on an admission sample than cTnT. Study 2 - IMD showed a small but significant rise at ten minutes after balloon inflation. HsTnT was significantly elevated the next day following PC!. Neither marker was related to number of stents/inflations, balloon pressure or length of inflation. Conclusions: The novel peptide IMD is elevated in ischaemia and infarction, but the rise is too small to be clinically useful. CGRP had a significant rise in ACS patients, but again of a small magnitude. The time course of their elevation is incompletely defined. HsTnT is more sensitive in ACS than cTnT on a presenting blood sample.
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Bena, Stefania. "Expression and function of the formyl peptide receptor 2 in experimental myocardial infarct." Thesis, Queen Mary, University of London, 2014. http://qmro.qmul.ac.uk/xmlui/handle/123456789/7905.
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In Acute Myocardial Infarction (AMI), inflammation is a prerequisite for healing but it can paradoxically extend tissue injury; hence it needs to be modulated. Here, we investigated the role of the pro resolving GPCR FPR2/ALX and its agonist Annexin A1 (AnxA1) in AMI using mice lacking of the Fpr2/3 genes and with an in-frame GFP gene ‘knocked-in’. We developed protocols aimed to determine GFP expression as an indication of Fpr2 gene activity. Also, the Left Anterior Descending Coronary Artery of male Fpr2/3 KO and littermate controls (WT) was occluded for 30min and re-opened for 90min. At the end tissue injury and inflammatory response were studied. A significant proportion of Fpr2/3 KO perished during the procedure. The rest survived up to 90 min and exhibited a larger infarct size, with higher troponin I and inflammation markers (KC, TNFα) than WT animals. At the end of reperfusion, Fpr2/3 KO displayed an unbalanced production of pro and anti-inflammatory lipids (higher PGE2, PGI2, LTB4 and attenuated PGA1, RvD2, LXA4) and a deregulated activation of the cardioprotective IL-6/JAK/STAT3 signalling. Administration of AnxA1 afforded cardioprotection (reduction of infarct size; Troponin I, Caspase3 activity and TNFα) in WT but not in Fpr2/3 KO. A parallel in vitro investigation on the functional FPR2/ALX domains required by AnxA1 and other agonists was also conducted. HEK-293 cells transfected with FPR1, FPR2/ALX and FPR1/FPR2 chimeric receptor were used and calcium flux, 4 pERK and gene modulation analysed. AnxA1 required the N-terminus and the II and III extracellular loops of FPR2/ALX to evoke canonical responses. SAA interacted/activated the I and the II extracellular loops of FPR2/ALX, whereas the compound 43 suffices the I extracellular loop. In summary, the FPR2/AnxA1 pathway exerts a protective role in AMI. AnxA1 mimetic that activated selective FPR2/ALX domains can be synthetize to prevent tissue damage caused by AMI.
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Dutra, Luiz Antonio [UNESP]. "Planejamento, síntese e avaliação farmacológica de novos compostos 1,2,5-oxadiazol-2-n-óxido úteis como preventivos de aterotrombose." Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/108423.
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Doenças cardiovasculares como infarto do miocárdio e acidente vascular encefálico ainda representam a principal causa de morte no Brasil. A aterosclerose é uma doença progressiva e silenciosa classificada como fator de risco para o desenvolvimento de doenças cardiovasculares. É caracterizada pelo aumento dos níveis de colesterol no plasma os quais são oxidados por radicais livres originando a lipoproteína de baixa densidade oxidada (LDLox). A fagocitose de LDLox por macrófagos permite a transformação destes em células espumosas, que são depositadas na camada íntima dos vasos. Após o rompimento do endotélio há o extravasamento do conteúdo da placa aterosclerótica para a circulação levando à formação de trombo. Este interrompe o fluxo sanguíneo em artérias e vasos, levando ao desenvolvimento de doenças cardiovasculares como infarto do miocárdio e acidente vascular encefálico. A terapia preventiva contra eventos aterotrombóticos é realizada com fármacos antiagregantes plaquetários. O ácido acetilsalicílico (AAS) é um dos fármacos mais utilizados na prevenção de aterotrombose, mas apresenta limitações como indução de ulcerações gástricas e bloqueio de somente uma via de agregação plaquetária. Neste sentido, e em continuidade com a linha de pesquisa visando à busca de novos fármacos antiagregantes plaquetários obtidos por estratégia de modificação molecular implantados no Laboratório de Pesquisa e Desenvolvimento de Fármacos (Lapdesf – UNESP Araraquara), realizou-se a hibridação molecular das subunidades presentes no AAS e furoxanos sendo ambas partes espaçadas pela subunidade N-acilhidrazona. O furoxano é conhecido por suas propriedades doadoras de óxido nítrico (NO) responsável pelo efeito antiagregante plaquetário. Assim, o objetivo deste trabalho é a síntese de novos compostos derivados do AAS, mais potentes e seguros para serem usados como antiagregantes plaquetários. Os ...
Cardiovascular diseases such as myocardial infarction and stroke still represents the leading cause of death in Brazil. Atherosclerosis is a silent progressive disease classified as a risk factor for developing cardiovascular diseases. It is characterized by increased levels of plasma cholesterol which are oxidized by free radicals resulting in oxidized low density lipoprotein (oxLDL). The oxLDL phagocytosis by macrophages allows for transformation into foam cells, which are deposited in the intima of vessels. After the disruption of the endothelium occurs the leak plaque’s contents into the circulation driving to thrombus formation. This blocks the blood flow in arteries and vessels, leading to the development of cardiovascular diseases such as myocardial infarction and stroke. The preventive therapy against atherothrombotic events is performed with antiplatelet drugs. Acetylsalicylic acid (ASA) is a drug commonly used to prevent atherothrombosis, but it has limitations such as induction of gastric ulcer and blocking only one route of platelet aggregation. Continuing goals finding new antiplatelet drugs obtained by molecular modification strategy implemented in the Laboratory of Drug Research and Development (Lapdesf - UNESP Araraquara), held the molecular hybridization of subunits present in AAS and furoxans being spaced by subunit N-acylhydrazone. The furoxano is known for its donor properties of nitric oxide (NO) responsible for the antiplatelet effect. The objective of this work is the synthesis of new compounds derived from AAS, most powerful and safe to use as antiplatelet agents. Compounds were synthesized using divergent route for obtaining derivatives furoxans, N-acilhidrazones spacers and the hybrid compounds. All compounds were purified and characterized by analytical methods such as, Infrared Absorption Spectroscopy, Mass Spectrometry and Nuclear Magnetic Resonance. N-acilhidrazones spacers was possible to perform the ...
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Dutra, Luiz Antonio. "Planejamento, síntese e avaliação farmacológica de novos compostos 1,2,5-oxadiazol-2-n-óxido úteis como preventivos de aterotrombose /." Araraquara, 2013. http://hdl.handle.net/11449/108423.
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Orientador: Jean Leandro dos SantosBanca: Leoberto Costa Tavares
Banca: Cíntia Duarte de Freitas Milagre
Resumo: Doenças cardiovasculares como infarto do miocárdio e acidente vascular encefálico ainda representam a principal causa de morte no Brasil. A aterosclerose é uma doença progressiva e silenciosa classificada como fator de risco para o desenvolvimento de doenças cardiovasculares. É caracterizada pelo aumento dos níveis de colesterol no plasma os quais são oxidados por radicais livres originando a lipoproteína de baixa densidade oxidada (LDLox). A fagocitose de LDLox por macrófagos permite a transformação destes em células espumosas, que são depositadas na camada íntima dos vasos. Após o rompimento do endotélio há o extravasamento do conteúdo da placa aterosclerótica para a circulação levando à formação de trombo. Este interrompe o fluxo sanguíneo em artérias e vasos, levando ao desenvolvimento de doenças cardiovasculares como infarto do miocárdio e acidente vascular encefálico. A terapia preventiva contra eventos aterotrombóticos é realizada com fármacos antiagregantes plaquetários. O ácido acetilsalicílico (AAS) é um dos fármacos mais utilizados na prevenção de aterotrombose, mas apresenta limitações como indução de ulcerações gástricas e bloqueio de somente uma via de agregação plaquetária. Neste sentido, e em continuidade com a linha de pesquisa visando à busca de novos fármacos antiagregantes plaquetários obtidos por estratégia de modificação molecular implantados no Laboratório de Pesquisa e Desenvolvimento de Fármacos (Lapdesf - UNESP Araraquara), realizou-se a hibridação molecular das subunidades presentes no AAS e furoxanos sendo ambas partes espaçadas pela subunidade N-acilhidrazona. O furoxano é conhecido por suas propriedades doadoras de óxido nítrico (NO) responsável pelo efeito antiagregante plaquetário. Assim, o objetivo deste trabalho é a síntese de novos compostos derivados do AAS, mais potentes e seguros para serem usados como antiagregantes plaquetários. Os ...
Abstract: Cardiovascular diseases such as myocardial infarction and stroke still represents the leading cause of death in Brazil. Atherosclerosis is a silent progressive disease classified as a risk factor for developing cardiovascular diseases. It is characterized by increased levels of plasma cholesterol which are oxidized by free radicals resulting in oxidized low density lipoprotein (oxLDL). The oxLDL phagocytosis by macrophages allows for transformation into foam cells, which are deposited in the intima of vessels. After the disruption of the endothelium occurs the leak plaque's contents into the circulation driving to thrombus formation. This blocks the blood flow in arteries and vessels, leading to the development of cardiovascular diseases such as myocardial infarction and stroke. The preventive therapy against atherothrombotic events is performed with antiplatelet drugs. Acetylsalicylic acid (ASA) is a drug commonly used to prevent atherothrombosis, but it has limitations such as induction of gastric ulcer and blocking only one route of platelet aggregation. Continuing goals finding new antiplatelet drugs obtained by molecular modification strategy implemented in the Laboratory of Drug Research and Development (Lapdesf - UNESP Araraquara), held the molecular hybridization of subunits present in AAS and furoxans being spaced by subunit N-acylhydrazone. The furoxano is known for its donor properties of nitric oxide (NO) responsible for the antiplatelet effect. The objective of this work is the synthesis of new compounds derived from AAS, most powerful and safe to use as antiplatelet agents. Compounds were synthesized using divergent route for obtaining derivatives furoxans, N-acilhidrazones spacers and the hybrid compounds. All compounds were purified and characterized by analytical methods such as, Infrared Absorption Spectroscopy, Mass Spectrometry and Nuclear Magnetic Resonance. N-acilhidrazones spacers was possible to perform the ...
Mestre
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Frewen, Sharon H. "The design and evaluation of a short-term group psychotherapy model for survivors of a first myocardial infarction." Thesis, Rhodes University, 2005. http://hdl.handle.net/10962/d1015041.
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There is extensive evidence that the rehabilitation of individuals with coronary heart disease needs to include psychological components to complement the exercise and dietary recommendations that are normally provided. However, psychological aspects have not been integrated into medical care in South Africa to any significant degree. Psychological interventions overseas have included the modification of the Type A behaviour pattern, stress management, cognitive restructuring, relaxation techniques, improved communication skills, the identification and expression of emotions, and emotional support. The aim of the present study was to design a short-term group intervention which incorporated these aspects and which included an exploration of the mind-body experience post infarct. In addition, the intervention aimed to increase participants' awareness of the compensatory dynamics of the Type A behaviour pattern. The intervention was tailored to South African conditions and was evaluated by means of a multiple case study design. The intervention was delivered to a group of nine coronary heart disease patients which included six survivors of myocardial infarction, the remaining participants having undergone a by-pass operation. Data included weekly feedback sheets evaluating each session, repeated measures on the Profile of Mood States, the Jenkins Activity Survey, a Spouse Rating Scale and extensive qualitative data on each participant including tape recordings of each session and data collected from a series of interviews before, during and after the programme. The feedback sheets and recordings of the sessions were used as a basis for recommendations for revising the content and structure of the programme for future use. Case narratives were written for three of the participants and provided an in-depth look at how and why individual changes did or did not occur in response to the intervention. In addition, the case narratives revealed the role played by the compensatory dynamics of the Type A behaviour pattern in complicating rehabilitation for survivors of myocardial infarction. Two participants were offered a series of individual sessions at 18-month follow-up and the material from these sessions was also used to aid in the interpretation of the data. The content of the 18-month follow-up sessions provided evidence for the importance of conducting a developmental analysis of the origins of low self-esteem and insecurity that maintain and drive the Type A behaviour pattern. In these sessions, this analysis provided the basis for a brief focused psychodynamic psychotherapy that facilitated marked changes that had not been achieved in the 12-week structured group intervention. It is recommended that future research investigate the use of brief psychodynamic psychotherapy on an individual basis as a complement to a group intervention focusing on psycho-education, building social support and management of problematic emotions in everyday situations.
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Condén, Emelie. "Type D Personality : Psychometric Properties of the DS14 and Associations with Ill Health and Coronary Heart Disease in General and Clinical Populations." Doctoral thesis, Uppsala universitet, Institutionen för neurovetenskap, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-233041.
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Type D personality, or distressed personality, refers to the joint tendency to experience negative emotions and to inhibit self-expression in social interactions. The overall aims of this thesis were to examine the impact of Type D personality on adolescents’ self-perceived health, to examine the factorial and temporal stability of the Type D personality construct DS14, and to clarify whether type D personality is an independent risk factor for recurrent myocardial infarction and all-cause mortality among patients with myocardial infarction. The prevalence of Type D personality in the adolescent population was 10.4% for boys and 14.6% for girls. Boys and girls with Type D personality were approximately twice as likely to report musculoskeletal pain and five times as likely to report psychosomatic symptoms. Adolescents with Type D personality were four times more likely to have sleep disturbances and to sleep fewer hours, especially on school nights. Among patients with myocardial infarction, the Swedish DS14 had stable structural validity. Our measurements confirmed the two-factor model of the DS14. However, the DS14 exhibited low temporal stability, especially when comparing the measurement obtained during hospitalization with the 1- and 12-month follow-up measurements. Among patients with myocardial infarction, the Framingham risk score had a strong predictive value for recurrent myocardial infarction, and a somewhat weaker predictive value for all-cause mortality. However, none of the previously proposed methods for the analysis of the DS14 Type D personality measurement predicted recurrent myocardial infarction or all-cause mortality, either in univariable analyses or in addition to the Framingham risk score. In conclusion, the present thesis found significant associations between the DS14 and psychosomatic symptoms in adolescents. However, the measurement exhibited a low stability over time and no predictive value for recurrent myocardial infarction and mortality among patients with myocardial infarction. Taken together, these results raise the question of whether the Swedish DS14 really is a measure of personality. An alternative explanation for the strong cross-sectional associations observed between the DS14 and psychosomatic symptoms might be that the DS14 functions as a pseudo-measure of ill health, or co-varies with depressive or psychosomatic characteristics.
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Dean, Stephanie A. "Regulation of angiotensin converting enzyme and angiotensin II type 1 receptor by 17beta-estradiol in female rats: Implications following experimental myocardial infarction." Thesis, University of Ottawa (Canada), 2005. http://hdl.handle.net/10393/26883.
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The present studies tested the hypothesis that 17beta-estradiol (E2) downregulates ACE and AT1R in several tissues important to cardiovascular regulation, including the brain and heart, and that this downregulation attenuates the progression of LV dysfunction following myocardial infarction (MI). In Experiment 1, female Wistar rats were randomized into one of four groups: (1) sham-ovariectomized (OVX); (2) OVX+vehicle (veh); (3) OVX+E2 replacement at physiological levels and (4) OVX+high E2. Five weeks following OVX, ACE and ATIR were increased 15-90% in the heart, several cardiovascular nuclei of the brain, kidney, abdominal aorta, adrenal and lung. These increases were prevented in all cases by E2 replacement at physiological levels and in most cases reversed to decreases by high E2. In Experiment 2, age-matched female Wistar rats underwent 1 of 3 treatments: no surgery (ovary-intact), OVX+veh treatment for two weeks, or OVX+high E2 treatment for two weeks. (Abstract shortened by UMI.)
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Hodson, Aimee Elizabeth. "Insulin Treatment Increases Myocardial Ceramide Accumulation and Disrupts Cardiometabolic Function." BYU ScholarsArchive, 2016. https://scholarsarchive.byu.edu/etd/5954.
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Prevalence of diabetes, especially type 2 diabetes mellitus (T2DM) is increasing worldwide. Millions of people are already affected by T2DM and estimates predict over half a billion people will likely be suffering from the disease by 2030. T2DM is associated with an increased risk of developing cardiovascular disease. Cardiovascular dysfunction is the leading cause of mortality among type 2 diabetics. Treatment for T2DM has changed over time. Though it was once known as insulin independent, a large portion of type 2 diabetics are now treated with insulin injections. However, type 2 diabetics treated with insulin are more likely to suffer from heart complications. Due to this, we sought to determine the specific effect of insulin and insulin-induced ceramide accrual on heart mitochondrial bioenergetics. To do so we used both in vitro and in vivo models. H9c2 cardiomyocytes and adult male mice were treated with insulin with or without the ceramide biosynthesis inhibitor myriocin. Mitochondrial bioenergetics were determined in permeabilized cardiomyocytes and myocardium. In this study we demonstrate that insulin induced ceramide accrual in both isolated cardiomyocytes and whole murine myocardium. We further found that insulin treatment is sufficient to disrupt mitochondrial respiration in both models. Inhibition of the ceramide accrual rescued mitochondrial respiration, indicating that ceramide is necessary for the insulin-induced alterations in heart mitochondrial respiration. These results suggest that insulin has a role in the development of heart complications associated with T2DM due to cardiomyocyte mitochondrial disruption. They also implicate ceramide as a possible mediator in the development of insulin-related heart disorders.
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Whittington, H. J. "The influence of age and type 2 diabetes on cardioprotective interventions against myocardial ischaemia-reperfusion injury." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1402476/.
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The background of the thesis is based on the conflicting results between bench and bedside regarding the susceptibility to myocardial infarction with old age and diabetes. In laboratories all over the world, strategies have been developed to protect the myocardium from this insult, including the use of ischaemic conditioning (short periods of ischaemia and reperfusion prior to or following lethal ischaemia) or the use of a variety of pharmacological agents. However, surprisingly, translating these effective cardioprotective treatments into the clinic has proved problematic. The main issue seems to be the fact that the experimental investigations have mainly used young, healthy animals while the human patients present often with a number of other risk factors, or comorbidities, such as type 2 diabetes and old age. Therefore the aim of this thesis was to investigate the susceptibility to ischaemia-reperfusion injury and the proficiency of cardioprotective strategies to protect the heart in the setting of ageing and type 2 diabetes. Utilizing a model of type 2 diabetes, the Goto-Kakizaki rat and its normoglycaemic control Wistar rat, within the range of 3 to 18 months of age, the Langendorff isolated heart model and in vivo coronary artery occlusion and reperfusion were employed to investigate the susceptibility to ischaemia-reperfusion injury. Mechanical or pharmacological cardioprotective strategies were also investigated in this setting and the mechanisms of the failed cardioprotection were examined further using in vitro techniques focusing on known pro survival signalling pathways within the myocardium. The ageing diabetic heart demonstrated an increased vulnerability to injury and was less amenable to protection by ischaemic conditioning. Pharmacological agents namely, metformin and sitagliptin appear to differentially protect the diabetic and non-diabetic heart, and this could be due to the underlying intracellular changes associated with ageing and diabetes.
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Geil, Dominik. "Charakterisierung der Ca 2+ -Transportaktivität des sarkoplasmatischen Retikulums nach experimentellem Myokardinfarkt." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 1998. http://dx.doi.org/10.18452/14393.
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Zur Charakterisierung der myokardialen SR Ca2+-Transportaktivität nach experimentellem Myokardinfarkt wurde 10-15 Wochen alten Ratten die linke Koronararterie unterbunden und sechs Wochen später die Funktion und Expression der Ca2+-ATPase des sarkoplasmatischen Retikulums untersucht. Ein Teil der Tiere wurde mit dem Carnitin-Palmitoyl-Transferase-1- Inhibitor Etomoxir behandelt, der die mitochondrale Oxidation von langkettigen Fettsäuren hemmt und dadurch verstärkt Glukoseoxidation bewirkt. Diese Stoffwechselumstellung sollte die Schädigung der myokardialen Funktion und die gestörte zelluläre Ca2+-Homöostase nach Myokardinfarkt vermindern. Die mit Etomoxir behandelten Tiere wiesen nach sechs Wochen eine deutlich verminderte Infarktgröße auf. Durch die CPT-1-Hemmung entstand eine starke biventrikuläre Hypertrophie. Darüber hinaus ergaben sich Hinweise auf den Erhalt einer normalen Wandspannung des linken Ventrikels und einer verbesserten Kontraktilität gegenüber der unbehandelten Gruppe. Unter Etomoxir zeigte die für die diastolische Ca2+ Senkung verantwortliche ATP-abhängige Ca2+-Rückbindung in das SR verbesserte Transportraten. Damit korrelierte der immunchemisch gemessene erhöhte SERCA2a-Proteinspiegel. Die Ergebnisse lassen vermuten, daß es infolge einer Behandlung mit Etomoxir nach Myokardinfarkt zu einer verbesserten Zellstoffwechsellage des ischämisch nicht irreversibel geschädigten Myokards kommt. Dafür scheint die verstärkte Glukoseoxidation bei Hemmung der Oxidation langkettiger Fettsäuren im Herzmuskel verantwortlich zu sein. Die Größe des infarzierten Areals wird begrenzt, dadurch lassen sich zum Teil verbesserte hämodynamische Parameter und gesteigerte SR Ca2+-Transportraten und SERCA2a-Proteinspiegel erklären. Auf die Hämodynamik hat sicherlich auch die durch Etomoxir erfolgte myokardiale Hypertrophie einen wesentlichen Einfluß. Für weitere Studien bleibt abzuklären, durch welchen Mechanismus Etomoxir seine verbessernde Wirkung nach Myokardinfarkt entfaltet. Außerdem ist zu prüfen, ob nach akutem Myokardinfarkt beim Menschen mit dem Prinzip der chronischen Verschiebung der myokardialen Substratverwertung von Fettsäure- nach Glukoseoxidation eine verbesserte Überlebensrate und das Hinauszögern bzw. Verhindern einer Dekompensation des Herzens zu erreichen ist.To characterise the activity of sarcoplasmic reticulum (SR) Ca2+ after myocardial infarction the left coronary artery of 10-15 week old male rats was ligated; six weeks later function and expression of the SR Ca2+-pump ATPase (SERCA2a) transport in the surviving myocardium was investigated. Part of the animals were treated with the carnithin palmitoyltransferase-1 (CPT-1) inhibitor etomoxir (8mg/kg/d for six weeks) to decrease the oxidation of long chain fatty acids. Due to the drug-induced shift from fatty acid to carbohydrate utilization an attenuated myocardial dysfunction and an improved SR Ca2+ handling homeostasis in the surviving myocardium could be expected. The etomoxir treated rats showed a decreased infarct size six weeks after coronary ligation. Due to CPT-1 inhibition a significant biventricular hypertrophy was observed. In addition, the treatment normalized elevated LVEDP and improved contractility. Compared to sham-operated controls treatment with etomoxir caused an enhanced SR Ca2+ uptake activity that correlated with increased immunoreactive SR Ca2+-ATPase levels. The results suggest that chronic inhibition of CPT-1 after myocardial infarction improves the metabolism of reversible damaged tissue. It appears that increased oxidation of glucose and inhibition of long chain fatty acid oxidation is responsible for this effect. Limitation of the infarct size induces improvement of haemodynamic parameters, increases SR Ca2+ uptake and protein levels of SERCA2a. Further studies are required to find out whether etomoxir is able to delay the development of congestive heart failure in humans and whether it could decrease mortality in patients after myocardial infarction.
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Messina, Julia Antoinette. "Molecular Localization of Hypoxia Inducible Factor-1-Alpha in Post-Ischemic Myocardium Following in Vivo Prolyl-4 Hydroxylase-2 Gene Silencing." VCU Scholars Compass, 2006. http://hdl.handle.net/10156/2197.
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Anderson, Donna. "Social support, quality of life and impact of illness on quality of life following myocardial infarction of coronary by-pass surgery /." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://proquest.umi.com/pqdweb?did=737023791&sid=4&Fmt=2&clientId=9268&RQT=309&VName=PQD.
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Govind, Satish C. "Myocardial Effects of Type 2 Diabetes, Co-morbidities, and Changing Loading Conditions : a Clinical Study by Tissue Velocity Echocardiography." Doctoral thesis, Stockholm : Skolan för teknik och hälsa, Kungliga Tekniska högskolan, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4359.
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Kakimoto, Yu. "Sorbin and SH3 Domain-containing Protein 2 Is Released from Infarcted Heart in Very Early Phase: Proteomic Analysis of Cardiac Tissues from Patients." Kyoto University, 2014. http://hdl.handle.net/2433/188650.
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Das, Rajiv. "Risk assessment and quality of care of patients with redefined acute myocardial infarction : a second evaluation of methods and management of acute coronary events study : EMMACE-2." Thesis, University of Leeds, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.416317.
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Hobbs, Daniel. "PATHOGENIC ROLE OF PHOSPHODIESTERASE TYPE 5 UPREGULATION IN CARDIAC ISCHEMIA/REPERFUSION INJURY." VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/106.
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Phosphodiesterase Type 5 (PDE5) inhibitors are cardioprotective against ischemia/reperfusion (I/R) injury. However, it remains uncertain if I/R affects PDE5. We hypothesized that generation of reactive oxygen species (ROS) during I/R leads to upregulation of PDE5, which contributes to pathological changes following acute myocardial infarction (AMI). Adult male ICR mice were subjected to 30 minutes of in vivo or ex vivo I/R. To examine the role of ROS, a subset of hearts were perfused with 100 µM hydrogen peroxide (H2O2). Expression and activity of PDE5, pPDE5, and cGMP-dependent protein kinase (PKG) were measured by Western blots and spectrophotometric assay. The results show that ischemia and I/R significantly increased expression of PDE5. H2O2 had no effect on PDE5 expression and activity but significantly increased PKG activity. We conclude that acute cardiac ischemia or I/R upregulate PDE5 independent of oxidant stress in the heart.
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Reyes, Levy Austin. "New mechanisms in nitric oxide synthase related endothelial dysfunction in the isolated heart." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1338346540.
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Hoxha, M. "THE POTENTIAL THERAPEUTIC ROLE OF MONTELUKAST AND NEW HYBRID AGENTS, TXA2 ANTAGONIST-COX-2 INHIBITORS IN CARDIOVASCULAR EVENTS." Doctoral thesis, Università degli Studi di Milano, 2016. http://hdl.handle.net/2434/347148.
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The main target of my PhD research project was to explore new alternatives to reduce the cardiovascular (CV) risk targeting the arachidonic acid metabolites. Hence, I have been part of two different projects, one studying multitarget compounds with balanced COXIB and TP receptor antagonist properties, and the other evaluating the potential role of a leukotriene (LT) antagonist drug such as montelukast in improving the CV outcome.
In reference to the first project, new multitarget compounds were synthesized at the University of Turin, by substituting the carboxylic function of Lumiracoxib. This strategy led to several new compounds, of which we have analyzed the platelet aggregation, total inositol phosphate production, COX-1 and COX-2 inhibitory activity. Out of all the studied compounds compound 18, the terazole derivative as well as compound 20 were the most active, with a decent balanced activity as COXIB and TP antagonist . Whereas, compound 32, displaying a functional group of terutroban did not accomplish our expectation to be a more potent TP antagonist with respect to compounds 7,18,20. Our main goal is to obtain new molecules with higher TP antagonist properties but at the same time retaining the COXIB activity. It is important to highlight that the therapeutic effect of these new compounds depend on the balance of two pharmacological profiles. The results we obtained demostrate that it is possible to have new chemical entities with higher TP antagonist potencies, and better balanced COX-2 selectivity. This approach will provide further benefits for patients with chronic pain taking a COXIB, and in patients with higher CV risk, like diabetics and hopefully can lead to a new generation of safer non steroidal antiinflammatory drugs.
The second project of my PhD was focused on a LT antagonist drug such as montelukast, which is a pharmacological alternative for patients suffering asthma, allergic rhinites and urticaria. We performed a retrospective study including patients exposed or not to montelukast for a total of eight hundred asthmatic patients to assess the potential role of montelukast in primary and secondary prevention of major CV events as ischemic stroke (IS) or myocardial infarction (MI). Each of the two subjects sample was further classified in patients with or without MI or IS based on their diagnosis according to the International Classification of Diseases (ICD). The myocardial infarction event rate was almost 6 fold higher in asthmatic patients not taking montelukast and 9 fold higher for ischemic stroke events. Drug used in these patients were also monitored in order to exclude potential confounders of the results. Overall, our results suggest a reduction of CV events by montelukast, including both MI and IS eventhough the study should be expanded to a larger number of subjects. Given their association with the inflammatory onset and amplification, LTs synthesis inhibitors or LT receptor antagonists such as montelukast could be consider as potential approach for CV diseases.
The results obtained during this three years of PhD cycle have shown that new innovative strategies targeting arachidonic acid metabolites can be implied to improve the CV outcome. There is still an unmet need for an anti-inflammatory treatment to reduce the CV risk, and these strategies can lead to new pharmacological approaches.
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Conti, Filipe Fernandes. "Efeitos do treinamento físico na cardiomiopatia e neuropatia autonômica associadas ao diabetes tipo 2 em fêmeas." Universidade Nove de Julho, 2016. http://bibliotecatede.uninove.br/handle/tede/1837.
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Diabetic patients frequently present cardiomyopathy and autonomic neuropathy, which increases mortality risk. On the other hand, exercise training has been suggested as a non-pharmacological tool in the prevention and treatment of type 2 diabetes. However, there are few studies that evaluated the effects of the three types of exercise training, aerobic, resistance or combined, mainly in the female sex, on diabetic cardiomyopathy and autonomic neuropathy. Thus, the objective of this study was to evaluate the effects of exercise training on cardiac and autonomic changes in female mice with a model of type 2 diabetes associated or not with myocardial infarction. To better understand and analyze the data, we divided the thesis into three protocols with specific objectives: 1) to describe the use of the ECG platform coupled to the echocardiogram machine for the acquisition of cardiac signals used in the analysis of heart rate variability in trained and sedentary (Protocol 1); 2) to analyze the effects of three types of exercise training (aerobic, resistance and combined) on cardiac and autonomic function parameters in ob/ob female mice, a model of type 2 diabetes (Protocol 2); 3) to evaluate the effects of aerobic exercise training on cardiac, autonomic, oxidative stress and inflammation parameters in ob/ob female mice submitted to myocardial infarction (MI) (Protocol 3). In protocol 1, a new approach to the acquisition of the RR interval in mice for the analysis of heart rate variability (HRV) using the echocardiographic machine was described. This method was tested in sedentary mice and trained mice submitted to a protocol of exercise training in the wheel (8 weeks), proving the improvement of cardiac function and autonomic modulation in the trained group. In the protocol 2, ob/ob animals (group O) presented additional body weight gain, hyperglycemia, glucose intolerance, reduction of sympathetic and vagal modulation and impairment in diastolic function parameters in relation to control animals (group C), showing a development of diabetic cardiomyopathy and diabetic autonomic neuropathy. The animals submitted to aerobic training (OTA group, treadmill: 40-60% maximum test, 8 weeks) and combined (OTC group, treadmill + ladder in alternate days: 40-60% maximum capacity, 8 weeks) showed improvement of diastolic function and myocardial global index (MPI – C: 0.48±0.01, O: 0.59±0.04, OTA: 0.37±0.02, OTR: 0.51±0,05; OTC: 0.33±0.02) in relation to the O and resistance (OTR) groups. There was an improvement in HRV in the OTA group in relation to the other ob/ob groups (cardiac vagal modulation (AF - O: 12±3, OTA: 20±6, OTR: 9±3, OTC: 7±2 ms2). Correlations between the improvement of the cardiac vagal modulation and the attenuation of the ventricular dysfunction were observed. In addition, the three types of exercise training attenuated the body weight gain in obese animals, as well as reduced glycemia and glucose intolerance. In protocol 3, myocardial infarction (OIS group) reduced exercise capacity, cardiac function (ejection fraction - O: 68.0±2.0 vs. OIS: 49.5±4.8%), and HRV (RMSSD - O: 5.9±0.7 vs. OIS: 0.7±1 ms; SD1 - O: 4.2±0.5 vs. OIS: 0.5±0.1 ms; SD2 - O: 13.6±2.1 vs. OIS: 2.0±7.5 ms), increased pro-inflammatory profile (increase of IL-17 and reduction of IL-10) and increased oxidative stress (lipoperoxidation- O: 2,92 ± 0,37 vs. OIS: 6.53 ± 1.05 μmol/mg protein; Protein oxidation - O: 8.46±0.61 vs. OIS: 13.02±1.20 nmol/mg protein) in ob/ob female mice. On the other hand, aerobic exercise training (treadmill: 40-60% maximal test, 4 weeks) post-MI in ob/ob females, despite not modifying cardiac function, improved exercise capacity, as well as HRV (RMSSD - 2.8±0.7 ms, SD1- 2.0±0.5 ms, SD2 – 7.5±1.2 ms), the inflammatory profile (reduction of IL-17 and increase of IL-10) and oxidative stress (lipoperoxidation - 4.18±0.3 μmol / mg protein; Protein oxidation - 10.18 ± 0.55 nmol / mg protein). In conclusion, even before the establishment of severe hyperglycemia, the development of type 2 diabetes in ob/ob females is associated with cardiac and autonomic dysfunctions, which are attenuated by resistance training, but mainly by aerobic or combined exercise training. In addition, myocardial infarction is associated with exacerbation of diabetic cardiomyopathy and autonomic neuropathy in females, and aerobic exercise training has a beneficial role in autonomic modulation, inflammation and cardiac oxidative stress in this condition. Taken together, our findings reinforce the important role of exercise training in managing cardiac and autonomic dysfunctions associated with complications of type 2 diabetes in females.
Pacientes diabéticos frequentemente apresentam cardiomiopatia e neuropatia autonômica, que aumentam risco de mortalidade. Por outro lado, o treinamento físico vem sendo sugerido como uma ferramenta não-farmacológica na prevenção e tratamento do diabetes tipo 2. Porém, são escassos os estudos que avaliaram os efeitos dos três tipos de treinamento físico, aeróbio, resistido ou combinado, principalmente no sexo feminino, na cardiopatia e neuropatia diabética. Dessa forma o objetivo deste estudo foi avaliar os efeitos do treinamento físico sobre as alterações cardíacas e autonômicas em camundongos fêmeas com um modelo de diabetes tipo 2 associado ou não ao infarto do miocárdio. Para melhor compreensão e análise dos dados, dividimos a tese em três protocolos com objetivos específicos: 1) descrever o uso da plataforma de ECG acoplado ao aparelho de ecocardiograma para aquisição dos sinais cardíacos usados na análise da variabilidade da frequência cardíaca em camundongos treinados e sedentários (Protocolo 1); 2) analisar os efeitos de três tipos de treinamento físico (aeróbio, resistido e combinado) sobre parâmetros de função cardíaca e autonômica em camundongos fêmeas ob/ob, um modelo de diabetes tipo 2 (Protocolo 2); 3) avaliar os efeitos do treinamento físico aeróbio sobre parâmetros de função cardíaca, autonômicos, de estresse oxidativo e de inflamação em camundongos fêmeas ob/ob submetido ao infarto do miocárdio (IM) (Protocolo 3). No protocolo 1, foi descrita uma nova abordagem para aquisição do intervalo RR em camundongos para a análise da variabilidade da frequência cardíaca (VFC) utilizando a aparelho de ecocardiograma. Este método foi testado em camundongos sedentários e submetidos à treinamento físico em roda (8 semanas) comprovando-se a melhora da função cardíaca e da modulação autonômica no grupo treinado. No protocolo 2, os animais ob/ob (grupo O) apresentaram aumento adicional de peso corporal, hiperglicemia, intolerância à glicose, redução da modulação simpática e vagal e prejuízo em parâmetros de função diastólica em relação a animais controles (grupo C), evidenciando o desenvolvimento de cardiomiopatia e neuropatia autonômica diabética. Os animais submetidos ao treinamento aeróbio (grupo OTA, esteira: 40-60% teste máximo, 8 semanas) e combinado (grupo OTC, esteira+escada em dias alternados: 40-60% capacidade máxima, 8 semanas) apresentaram melhora da função diastólica e global cardíaca (Índice de performance miocárdica (MPI) - C: 0,48±0,01; O: 0,59±0,04; OTA: 0,37±0,02; OTR: 0,51±0,05; OTC: 0,33±0,02) em relação aos grupos O e treinado resistido (OTR). Foi observada melhora da VFC no grupo OTA em relação aos demais grupos ob/ob (Modulação vagal cardíaca (AF) - O: 12±3; OTA: 20±6; OTR: 9±3; OTC: 7±2 ms2). Foram observadas correlações entre a melhora da modulação vagal cardíaca com a atenuação da disfunção ventricular. Além disto, os três tipos de treinamento físico atenuaram o ganho de peso corporal nos animais obesos, além de reduzirem a glicemia e a intolerância à glicose. No protocolo 3, o infarto do miocárdio (grupo OIS) promoveu redução da capacidade de exercício, da função cardíaca (Fração de ejeção- O: 68,0±2,0 vs. OIS: 49,5±4,8 %) e da VFC (RMSSD- O: 5,9±0,7 vs. OIS: 0,7±01 ms; SD1- O: 4,2±0,5 vs. OIS: 0,5±0,1 ms; SD2 - O: 13,6±2,1 vs. OIS: 2,0±7,5 ms) um perfil pró inflamatório (aumento de IL-17 e redução de IL-10) e aumento de estresse oxidativo (Lipoperoxidação- O: 2,92±0,37 vs. OIS: 6,53±1,05 µmoles/mg proteína; Oxidação de proteínas- O: 8,46±0,61 vs. OIS: 13,02±1,20 nmol/mg proteína) em camundongos fêmeas ob/ob. Por outro lado, o treinamento físico aeróbio (esteira: 40-60% teste máximo, 4 semanas) pós IM em fêmeas ob/ob, apesar de não modificar a função cardíaca, melhorou a capacidade de exercício, bem como a VFC (RMSSD- 2,8±0,7 ms; SD1- 2,0±0,5 ms; SD2 - 7,5±1,2 ms), o perfil inflamatório (redução de IL-17 e aumento de IL-10) e de estresse oxidativo (Lipoperoxidação- 4,18±0,3 µmoles/mg proteína; Oxidação de proteínas- 10,18±0,55 nmol/mg proteína). Concluindo, os resultados evidenciam que mesmo antes do estabelecimento de hiperglicemia severa, o desenvolvimento do diabetes tipo 2 em fêmeas ob/ob está associado a disfunções cardíacas e autonômicas, que são atenuadas pelo treinamento físico resistido, mas principalmente pelo aeróbio ou combinado. Além disto, o infarto do miocárdio está associado à exacerbação da cardiomiopatia e neuropatia autonômica diabética em fêmeas, tendo o treinamento físico aeróbio um papel benéfico na modulação autonômica, na inflamação e no estresse oxidativo cardíaco nessa condição. Em conjunto, nossos achados reforçam o importante papel do treinamento físico no manejo das disfunções cardíacas e autonômicas associadas as complicações do diabetes tipo 2 no sexo feminino.
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Wagner, Claudia Karin. "Kardioprotektion durch Postkonditionierung gesunder Rattenherzen sowie von Herzen mit kardiovaskulären Risikofaktoren: Charakterisierung der Signaltransduktion unter besonderer Betrachtung von PI3-K/Akt, mTOR, ERK1/2 und GSK-3ß." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2008. http://nbn-resolving.de/urn:nbn:de:bsz:14-ds-1226858602601-68237.
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In den ersten Versuchsreihen der hier vorliegenden Arbeit bestätigte sich, dass im in vitro Modell die klassische ischämische Präkonditionierung kardioprotektiv wirkt. Die Präkonditionierung bewirkte eine Infarktgrößenreduktion um 54 %; dies wird durch Literaturangaben bestätigt. Die Postkonditionierung dagegen, trotz drei verschiedener Postkonditionierungsprotokolle, ist am isoliert perfundierten Rattenherzen nicht protektiv. Im in vivo Rattenherz-Modell wurden die Präkonditionierung und die klinisch relevantere Postkonditionierung gegenüberstellend untersucht. Hier zeigte sich, dass die 3 Reperfusions-/Ischämiezyklen für jeweils 30 Sekunden der Postkonditionierung genauso protektiv wie die Präkonditionierung wirken. Infarktgrößen- und biochemische Untersuchungen belegen, dass hierbei die PI3-Kinase ein wichtiges Signaltransduktionselement ist, da einerseits durch die Inhibition der PI3-Kinase mittels Wortmannin die Infarktgrößenreduktion vollständig aufgehoben war und andererseits nach einer 1,5-minütigen Reperfusion eine vermehrte Phosphorylierung der Akt im Western-Blot auftrat. Des Weiteren konnte erstmals die Inaktivierung der GSK-3ß durch eine verstärkte Phosphorylierung über einen PI3-Kinase-vermittelten Signaltransduktionsweg nachgewiesen werden. Die Zugabe des spezifischen Inhibitors TDZD-8 der GSK-3ß verringert ebenfalls die Infarktgröße signifikant. Auch konnte zum ersten Mal gezeigt werden, dass das mammalian target of Rapamycin in der Postkonditionierung des in vivo Rattenherzens eine wichtige Rolle zu spielen scheint. Außerdem konnte neben dem PI3-Kinase/Akt-Signaltransduktionsweg auch die Beteiligung des MEK1/2-ERK1/2–Wegs als Signaltransduktionsweg der Postkonditionierung im in vivo Rattenherzen nachgewiesen werden. Erstmals wurde die Apoptose in einem in vivo Herzen nach regionaler Ischämie untersucht. Die Ergebnisse des TUNEL-Tests und der Western-Blot-Analysen zeigen eine unterdrückte Apoptose durch die Postkonditionierung. Ein weiterer Teil der vorliegenden Arbeit widmete sich der Untersuchung der Postkonditionierung in pathologischen Rattenherzen. Im Gegensatz zu gesunden Herzen schlug die Postkonditionierung in hypertrophiertem Myokardium von spontan-hypertensiven Ratten mit einer signifikant arteriellen Hypertension fehl. Diese Blockierung der Kardioprotektion zeigte sich durch die fehlende Reduzierung der Infarktgröße trotz unterschiedlicher Postkonditionierungsprotokolle (3x30’’ und 6x10’’ R/I) und unterschiedlich langer Ischämiedauern (20 und 30 Minuten). Gleichfalls war auch die Phosphorylierung der GSK-3ß aufgehoben. Als Modell des metabolischen Syndroms wurde die WOKW-Ratte untersucht. Diese Ratten entwickeln in sehr jungem Alter klassische Symptome wie Dyslipidämie, Hyperinsulinämie und Fettsucht. Wie bei der Herzhypertrophie war auch beim Modell des metabolischen Syndroms die Postkonditionierung - mit 3 Reperfusions-/ Ischämiezyklen für jeweils 30 Sekunden - blockiert. Dabei konnte weder eine Infarktgrößenreduktion noch eine vermehrte Phosphorylierung der GSK-3ß nachgewiesen werden. Die Ergebnisse der vorliegenden Arbeit erlauben die Schlußfolgerung, dass das Substrat der GSK-3ß, die mPTP des Mitochondriums, eine „Schlüsselrolle“ in der Apoptose innehat - die Postkonditionierung vermindert nicht nur die Nekrose, sondern reduziert auch die Apoptose. Bemerkenswert und potentiell von klinischer Bedeutung ist die Beobachtung, dass bei Vorliegen von Risikofaktoren, wie arterielle Hypertonie und metabolischem Syndrom, solche Schutzmechanismen des Herzens aufgehoben sind. Diese Erkenntnisse sind im Hinblick auf die Therapie am Menschen von großer Bedeutung. Ob langfristig einzelne Komponenten der Signaltransduktionswege, wie PI3-Kinase, Akt, mTOR, ERK1/2 oder GSK-3ß, Angriffspunkte einer pharmakologischen Therapie sein könnten, muß in weiteren Untersuchungen geklärt werden.
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Addisu, Anteneh. "Natriuretic peptides as a humoral link between the heart and the gastrointestinal system." [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002406.
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Gunter, Bryan R., Kristen A. Butler, Rick L. Wallace, Steven M. Smith, and Sam Harirforoosh. "NSAIDs-Induced Cardio- and Cerebro-Vascular Adverse Events: a Meta-analysis." Digital Commons @ East Tennessee State University, 2017. https://doi.org/10.1111/jcpt.12484.
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What is known and objective: Although non-steroidal anti-inflammatory drugs (NSAIDs) have been studied in randomized, controlled trials and meta-analyses in an effort to determine their cardiovascular (CV) risks, no consensus has been reached. These studies continue to raise questions, including whether cyclooxygenase-2 (COX-2) selectivity plays a role in conferring CV risk. We performed a meta-analysis of current literature to determine whether COX-2 selectivity leads to an increased CV risk.
Methods: We utilized randomized, controlled trials and prospective cohort studies. We selected eight NSAIDs based on popularity and COX selectivity and conducted a search of the MEDLINE, EMBASE, and Cochrane databases. Primary endpoints included any myocardial infarction (MI), any stroke, CV death, and a combination of all three (composite CV outcomes). Twenty-six studies were found that met inclusion and exclusion criteria. Comparisons were made between all included drugs, against placebo, and against non-selective NSAIDs (nsNSAIDs). Drugs were also compared against COX-2 selective inhibitors (COXIBs) with and without inclusion of rofecoxib.
Results and discussion: Incidence of MI was increased by rofecoxib in all comparison categories [all NSAIDs (OR: 1·811, 95% CI: 1·379-2·378), placebo (OR: 1·655: 95% CI: 1·029-2·661), nsNSAIDs (OR: 2·155, 95% CI: 1·146-4·053), and COXIBs (OR: 1·800, 95% CI: 1·217-2·662)], but was decreased by celecoxib and naproxen in the COXIB comparison [(OR: 0·583, 95% CI: 0·396-0·857) and (OR: 0·609, 95% CI: 0·375-0·989, respectively]. Incidence of stroke was increased by rofecoxib in comparisons with all NSAIDs and other COXIBs [(OR: 1·488, 95% CI: 1·027-2·155) and (OR: 1·933, 95% CI: 1·052-3·549), respectively]. Incidence of stroke was decreased by celecoxib when compared with all NSAIDs, nsNSAIDs, and COXIBs [(OR: 0·603, 95% CI: 0·410-0·887), (OR: 0·517, 95% CI: 0·287-0·929), and (OR: 0·509, 95% CI: 0·280-0·925), respectively]. No NSAID reached statistical significance in regard to CV death. Incidence of the composite endpoint was increased by rofecoxib when compared against all NSAIDs, placebo, and other COXIBs [(OR: 1·612, 95% CI: 1·313-1·981), (OR: 1·572, 95% CI: 1·123-2·201) and (OR: 1·838, 95% CI: 1·323-2·554), respectively]. Incidence of composite endpoint was decreased by celecoxib in the all NSAIDs and COXIBs comparisons [(OR: 0·805, 95% CI: 0·658-0·986) and (OR: 0·557, 95% CI: 0.404-0.767), respectively]. When rofecoxib was removed from the COXIBs group, no difference was found with any comparison, suggesting rofecoxib skewed the data.
What is new and conclusion: This instead of the meta-analysis suggests that COX-2 selectivity may not play a role in the CV risk of NSAIDs. Rofecoxib was the only drug to demonstrate harm and skewed the data of the COX-2 selective group.
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Rezende, Paulo Cury. "Expressão do precondicionamento isquêmico em pacientes com diabetes mellitus tipo 2 e doença arterial coronariana." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/5/5131/tde-06012016-135102/.
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Introdução: Acredita-se que o diabetes mellitus possa alterar mecanismos celulares do miocárdio tornando-o mais sensível a um insulto isquêmico, e que esta menor resistência do miocárdio isquêmico induzido pelo diabetes possa ser um dos motivos para o pior prognóstico observado em pacientes com doença arterial coronariana e diabetes. Um dos principais mecanismos adaptativos protetores do miocárdio é o precondicionamento isquêmico, sendo este desencadeado por curtos períodos de isquemia seguidos por reperfusão e que tornam o tecido mais resistente a um insulto isquêmico grave e prolongado. Em humanos, o precondicionamento isquêmico pode ser observado durante testes ergométricos sequenciais, nos quais a melhora em parâmetros isquêmicos no segundo teste ergométrico quando comparado ao primeiro é uma metodologia consagrada para o estudo clínico deste fenômeno. Estudos experimentais demonstram resultados controversos em relação à interferência do diabetes sobre o fenômeno do precondicionamento, e estudos com humanos são escassos e inconclusivos. Assim, ainda é incerto se o diabetes pode afetar a expressão do precondicionamento isquêmico em pacientes com doença arterial coronariana. Objetivos: Identificar se o diabetes mellitus interfere no fenômeno do precondicionamento isquêmico em pacientes com doença arterial coronariana. Métodos: Pacientes com doença arterial coronariana comprovada por cineangiocoronariografia diagnóstica, função ventricular sistólica preservada e com angina ou teste ergométrico positivo para isquemia miocárdica foram submetidos a dois testes ergométricos sequenciais com intervalo de 30 minutos. Parâmetros isquêmicos foram comparados entre pacientes com e sem diabetes mellitus. O precondicionamento isquêmico foi considerado presente quando o tempo para a depressão em 1,0 mm do segmento ST (T-1mm) foi maior no segundo teste sequencial comparado ao primeiro. Também se mensurou o duplo-produto (frequência cardíaca multiplicada pela pressão arterial sistólica) no momento do T- 1mm. Os testes foram analisados por dois cardiologistas experientes, independentes. Resultados: De 2.140 pacientes consecutivos com doença arterial coronariana, 361 apresentavam critérios para inclusão nesse estudo. Destes, 174 pacientes (64,2 ± 7,6 anos) foram submetidos aos testes ergométricos sequenciais para identificação e caracterização do precondicionamento isquêmico; 86 apresentavam diabetes mellitus (grupo 1) e 88 não apresentavam diabetes mellitus (grupo 2). Os dois grupos foram semelhantes em relação às principais características demográficas, com exceção de infarto do miocárdio prévio e perfil lipídico. No primeiro grupo, 62 pacientes (72,1%) manifestaram o precondicionamento isquêmico e no segundo, 60 (68,2%) manifestaram o precondicionamento isquêmico (P=0,62). Analisando-se os pacientes que expressaram o fenômeno, a melhora do T-1mm foi similar entre os dois grupos (média da melhora do tempo entre os testes 1 e 2: 79,4 ± 47,6 x 65,5 ± 36,4 segundos, respectivamente para os grupos 1 e 2, P=0,12). Em relação ao duploproduto no momento do T-1mm, os pacientes com diabetes apresentaram melhora expressiva em relação aos pacientes sem diabetes (média da melhora do duploproduto 3011 ± 2430 x 2081 ± 2139 bpm x mmHg, respectivamente para os grupos 1 e 2, P=0,01). A análise da melhora das arritmias e da morfologia da depressão do segmento ST nos testes ergométricos sequenciais não mostrou diferenças entre os dois grupos de pacientes. Conclusão: Neste estudo, o diabetes mellitus tipo 2 não impediu o surgimento do PI. Além disso, o diabetes esteve associado à melhora significativa do esforço cardíaco e do consumo miocárdico de oxigênio, caracterizados pelo duplo-produto .Background: It\'s postulated that diabetes mellitus may impair myocardial cellular mechanisms turning it more sensitive to ischemic injuries, and that this lower resistance of the ischemic myocardium induced by diabetes may be one reason for the poor prognosis observed in patients with both coronary artery disease and diabetes. One major adaptive myocardial protective mechanism is ischemic preconditioning, which is triggered by brief ischemia followed by reperfusion that turns the myocardium more resistant to a prolonged ischemic insult. In humans, ischemic preconditioning can be observed during sequential exercise tests, in which the improvement in ischemic parameters in the second exercise test compared to the first is a methodology devoted to the clinical study of the phenomenon. However, experimental studies have shown conflicting results about the interference of diabetes on ischemic preconditioning, and the few human studies are scarce and inconclusive. Thus, it\'s still uncertain whether diabetes may affect ischemic preconditioning in coronary artery disease patients. Objectives: Identify whether type 2 diabetes mellitus intervenes on myocardial ischemic preconditioning in symptomatic coronary artery disease patients. Methods: Symptomatic multivessel coronary artery disease patients with preserved systolic ventricular function and a positive exercise test underwent two sequential exercise tests to demonstrate ischemic preconditioning. Tests were performed with a 30 minutes interval between them. Ischemic parameters were compared among patients with and without type 2 diabetes mellitus. Ischemic preconditioning was considered present when the time to 1.0 mm ST deviation (T-1mm) was greater in the second of 2 exercise tests. Rate pressure-product (heart rate multiplied by systolic arterial pressure) at T-1mm was also assessed. Sequential exercise tests were analyzed by 2 independent cardiologists. Results: Of the 2,140 consecutive coronary artery disease patients screened, 361 met inclusion criteria, and 174 patients (64.2 ± 7.6 years) completed the study protocol. Of these, 86 had the diagnosis of type 2 diabetes. The 2 groups were similar regarding the main demographic characteristics, except for the rate of previous myocardial infarction and lipid profile. Among diabetic patients, 62 (72.1%) manifested an improvement in ischemic parameters consistent with ischemic preconditioning, whereas among nondiabetic patients, 60 (68.2%) manifested ischemic preconditioning (P=0.62). The analysis of patients who demonstrated ischemic preconditioning showed similar improvement in the time to 1.0 mm ST deviation between diabetic and nondiabetic groups (79.4 ± 47.6 vs 65.5 ± 36.4 sec, respectively, P=0.12). Regarding rate pressure-product, the improvement was greater in diabetic compared to nondiabetic patients (3011 ± 2430 vs 2081 ± 2139 bpm x mmHg, respectively, P=0.01). The analysis of arrhythmias and ST-segment deviation morphology during sequential exercise tests did not show differences between the 2 groups of patients. Conclusion: In this study, type 2 diabetes mellitus did not prevent the occurrence of ischemic preconditioning. In addition, diabetes was associated with significant improvement in cardiac stress and myocardial oxygen consumption, characterized by rate pressure-product
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Philouze, Clothilde. "Dépistage des altérations précoces de la fonction régionale myocardique par échocardiographie de stress et effet d’une intervention par supplémentation en vitamine D3 dans le diabète de type 2 : approche translationnelle." Thesis, Avignon, 2018. http://www.theses.fr/2018AVIG0346/document.
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Le diabète est aujourd’hui la 7ème cause de mortalité dans le monde. Dans cette population, la cardiomyopathie diabétique est la principale cause de morbi-mortalité. Le développement de cette complication débutant dès l’apparition du diabète, un dépistage et une prise en charge précoces de cette pathologie sont donc de première importance et sont les deux objectifs visés par ces travaux. La première étude que nous avons réalisée a permis de démontrer l’utilité d’une évaluation compréhensive de la fonction régionale myocardique gauche par 2D speckle-tracking imaging, en conditions de stress à la dobutamine, dans le dépistage précoce de la cardiomyopathie diabétique chez des patients diabétiques de type 2 asymptomatiques. La deuxième partie de ces travaux a, quant à elle, donné lieu à deux études. L’étude clinique a permis de mettre en évidence une amélioration de la réponse au stress de la fonction régionale myocardique après 3 mois de supplémentation en vitamine D3 chez des patients carencés. L’étude expérimentale a, pour sa part, souligné les effets bénéfiques sur le remodelage et la fonction cardiaques de cette supplémentation, en prévention secondaire, dans un modèle murin de diabète de type 2 induit par un régime gras et sucré. Par ailleurs, cette étude a mis en lumière l’implication potentielle d’une modulation des taux myocardiques en espèces lipotoxiques par la vitamine D3 dans ces effets. L’ensemble de ces travaux de thèse a ainsi permis, d’une part, de proposer une technique de dépistage des signes précoces d’altération de la fonction cardiaque chez le patient diabétique de type 2 et, d’autre part, de montrer les effets bénéfiques d’une supplémentation en vitamine D3 dans ce contexteDiabetes has reached the 7th place in the world’s top ten mortality causes. In this population, morbi-mortality mainly originates from diabetic cardiomyopathy. This complication evolving from the onset of diabetes, early diagnosis and care are of paramount importance and are the two purposes of this work. In our first study, we demonstrated the relevance of a comprehensive 2D speckle-tracking imaging analysis, under dobutamine stress, in unmasking early left ventricular regional myocardial dysfunction in a population of asymptomatic type 2 diabetic patients. In the second part of this work, we performed two studies. In the first one, we brought to light an improvement of regional myocardial function response to dobutamine stress after a three-month vitamin D3 supplementation protocol, in deficient patients. The second study was performed in a mouse model of diet-induced type 2 diabetes. In this last work, we put forward the beneficial effects of vitamin D3 supplementation, in secondary prevention, on cardiac remodeling and function. These cardioprotective effects may be, at least in part, on account of modulatory effects of vitamin D3 on myocardial lipotoxic species levels. This whole work allow us to propose a tool enabling recognition of early cardiac function impairments in type 2 diabetic patients and to demonstrate the beneficial effects of vitamin D3 supplementation in this context
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Bakhta, Oussama. "Métabolites circulants induits par le conditionnement ischémique à distance et mécanismes cardioprotecteurs de la colchicine à la phase aigue de l'infarctus du myocarde Metabolic Signature of Remote Ischemic Preconditioning Involving a Cocktail of Amino Acids and Biogenic Amines Cardioprotective role of colchicine against inflammatory injury in a rat 2 model of acute myocardial infarction." Thesis, Angers, 2017. http://www.theses.fr/2017ANGE0089.
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La reperfusion précoce à la phase aiguë de l’infarctus du myocarde améliore le pronostic des patients. Elle induit cependant une partie des lésions d’ischémie-reperfusion (I/R) liées à l’activation de mécanismes métaboliques et inflammatoires. Le conditionnement ischémique à distance (RIC) d’une part et les approches pharmacologiques d’autre part, constituent un espoir dans la prévention des lésions de reperfusion contre lesquelles nous ne disposons pas de traitement validé chez l’homme. L’objectif de cette thèse était d’explorer ces stratégies de cardioprotection à la phase aiguë de l’infarctus du myocarde. Grace à une approche métabolomique, nous avons identifié la kynurénine et glycine comme métabolites associés au RIC sur des plasmas de rats et confirmés dans une cohorte de patients. Nous avons ainsi validé in vivo l’action bénéfique de la kynurénine et de la glycine dans un modèle d’infarctus du myocarde. Nous avons ensuite étudié la modulation de la voie des kynurénines dans la cardioprotection induite par le RIC. Nous avons observé une activation de la voie de synthèse du NAD+ associée à une déacétylation des protéines mitochondriales hépatiques. Dans un dernier travail réalisé in vivo et in vitro, nous avons étudié le rôle cardioprotecteur de la colchicine dans l’I/R et analysé ces effets sur la modulation de l’inflammation et l’activation des voies de survieThe introduction of early reperfusion in the acute phase of myocardial infarction has improved the prognosis of patients. However, it induces irreversible damages called ischemia-reperfusion (I / R) injury followed by myocardial metabolic and inflammatory disorders. Remote ischemic conditioning (RIC) on the one hand and pharmacological approaches on the other hand, constitute a hope in the prevention of reperfusion injury against which we do not have validated treatment in humans.The aim of this thesis was to explore cardioprotection strategies in the acute phase of myocardial infarction. Using a metabolomics approach, we identified kynurenine and glycine as RIC-associated metabolites in rat plasmas and confirmed in a cohort of patients. We have also validated in vivo the beneficial effect of kynurenine and glycine in a model of myocardial infarction. We then studied the modulation of the kynurenine pathway in RIC-induced cardioprotection. We observed an activation of the NAD + synthesis pathway associated with deacetylation of hepatic mitochondrial proteins. In a last work carried out in vivo and in vitro, we studied the cardioprotective role of colchicine in I / R and analyzed its immunomodulatory effect and activation of survival pathways
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Labbé, Vincent. "Risques thrombotiques et hémodynamiques chez les patients hospitalisés en réanimation présentant une fibrillation atriale de novo au cours d’un sepsis : caractérisation, stratification et stratégies thérapeutiques." Electronic Thesis or Diss., Sorbonne université, 2023. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2023SORUS556.pdf.
Full textAbstract:
Objectifs Les patients hospitalisés en réanimation pour un sepsis sont à haut risque d’accidents thrombotiques (AT) intéressant l’ensemble des circulations (grande, coronaire, petite). Nous souhaitons étudier ce risque thrombotique lors du sepsis (i) au sein de la grande circulation chez les patients présentant une fibrillation atriale de novo (FAN), (ii) au sein de la circulation coronaire chez les patients présentant un infarctus du myocarde (IDM) et (iii) au sein de la petite circulation chez les patients COVID-19 sévère. Par ailleurs, si le risque d’AT pose la question de l’intérêt de la thromboprophylaxie à dose croissante, l’évaluation du risque hémorragique en regard devra être systématique afin d’établir la balance bénéfice/risque d’un tel traitement. Méthodes Nous avons investigué le risque d’événements cardio-vasculaires majeurs (caractérisation et stratification) incluant les ATs, les hémorragies sévères, et le décès au sein de trois populations de patients septiques présentant une FAN, un IDM, ou une COVID-19 sévère par l’étude (i) de marqueurs tels que la dysfonction de l’auricule gauche à l’échocardiographie trans-oesophagienne (ETO) et la troponine cardiaque, et (ii) des scores de risque thrombotique et hémorragique utilisés chez les patients de cardiologie. Nous avons mené une enquête de pratique sur la gestion du risque thrombotique chez les patients ayant une FA lors d’un sepsis. Enfin nous avons effectué deux essais thérapeutiques : l’essai CAFS (Control Atrial Fibrillation Sepsis) de supériorité multicentrique randomisé, contrôlé comparant trois stratégies usuelles de prévention du risque hémodynamique chez les patients en choc septique présentant une FAN (en cours d’inclusion), et l’essai ANTICOVID (ANTIcoagulation in patients with hypoxemic COVID-19 pneumonia) comparant trois stratégies de traitement anticoagulant avec escalade de dose chez des patients présentant une pneumonie hypoxémiante COVID-19. Résultats Le risque d’évènements cardio-vasculaires majeures est élevé au cours d’un sepsis. Chez les patients en FAN, les approches cardiologiques de stratification des risques thrombotiques (anomalies ETO, score CHA2DS2-VASc) et hémorragiques (score HAS-BLED) semblent limitées. Une approche individualisée basée sur l’ETO et le score CHA2DS2-VASc pourrait néanmoins être intéressante. Ce travail a également mieux caractérisé le risque de formation d’un thrombus intra-cardiaque (absence de thrombus dans les 48 h suivant le début de la FA, prévalence rare de la sidération post cardioversion de l’auricule gauche). Enfin, nous avons confirmé l’hétérogénéité de prise en charge des risques hémodynamiques et thrombotiques justifiant la réalisation d’essais thérapeutiques. Chez les patients ayant un IDM au cours d’un sepsis, les approches cardiologiques usuelles de stratification des risques thrombotiques (scores GRACE et TIMI) semblent également limitées. En pratique usuelle, une stratégie invasive avec revascularisation coronaire précoce est très rarement effectuée. Chez les patients explorés par angiographie coronaire, l’incidence d’une coronaropathie obstructive est importante. Chez les patients présentant une pneumonie hypoxémiante COVID-19, le traitement anticoagulant préventif à dose forte, comparé au traitement anticoagulant préventif à dose standard, a été associé à un meilleur bénéfice clinique net, en raison d’une diminution du risque de thrombose et d'un faible risque hémorragique. Le traitement anticoagulant curatif n'a pas apporté de bénéfice supplémentaire. Conclusions Sur une base physiopathologique pro-thrombotique inhérente au sepsis, ce travail a permis (i) de mieux caractériser certaines situations à haut risque thrombotique (FAN, IDM, COVID sévère), (ii) élaborer des stratégies individuelles thérapeutiques de prévention du risque thrombotique (COVID-19), et (iii) poser les bases de futurs essais au sein de populations spécifiques à très haut risque thrombotiqueObjectives Patients admitted to intensive care units with sepsis are at high risk of thrombotic events (TEs) throughout the circulatory systems (systemic, coronary, and pulmonary). We aimed to investigate the thrombotic risk during sepsis (i) within the systemic circulation in patients with new-onset atrial fibrillation (NOAF), (ii) within the coronary circulation in patients with acute myocardial infarction (MI), and (iii) within the pulmonary circulation in patients with severe COVID-19. Furthermore, while the risk of TE raises the question of whether thromboprophylaxis doses should be escalated, assessment of associated bleeding risk should be systematic in order to establish the benefit/risk balance of such treatment. Methods We investigated the risk of major cardiovascular events (risk characterization and stratification), including AT, major bleeding and death in three populations of septic patients with NOAF, MI or severe COVID-19 by studying (i) markers such as left atrial dysfunction on transesophageal echocardiography (TEE) and cardiac troponin, and (ii) thrombotic and hemorrhagic risk scores used in cardiology patients. We conducted a practice survey on thrombotic risk management in patients with de NOAF during sepsis. Finally, we carried out two therapeutic trials: the CAFS (Control Atrial Fibrillation Sepsis) multicenter, randomized, controlled superiority trial comparing three usual strategies to prevent hemodynamic risk with NOAF during septic shock (currently being included), and the ANTICOVID (ANTIcoagulation in patients with hypoxemic COVID-19 pneumonia) multicenter, randomized, controlled superiority trial comparing three anticoagulation strategies with dose escalation in patients with hypoxemic COVID-19 pneumonia Results Our work confirmed the high risk of major cardiovascular events during sepsis. In patients with NOAF, cardiological approaches to thrombotic (TEE abnormalities, CHA2DS2-VASc score) and hemorrhagic (HAS-BLED score) risk stratification seem limited. An individualized approach with TEE based on the CHA2DS2-VASc score could nevertheless be of interest. This work also better characterized the risk of intra-cardiac thrombus formation (absence of thrombus within 48 h of AF onset, low prevalence of post-cardioversion left atrial stunning). Finally, we confirmed the heterogeneity of hemodynamic and thrombotic risks management, calling for randomized trials. In patients with MI during sepsis, cardiological approaches to thrombotic risk stratification (GRACE and TIMI scores) also appear limited. In usual practice, an invasive strategy involving early coronary revascularization is very uncommon. In patients investigated using coronary angiography, the incidence of obstructive coronary artery disease is high. In patients with hypoxemic COVID-19 pneumonia, high-dose prophylactic anticoagulation, provided a better net clinical benefit driven by a 4-fold reduction in de novo thrombosis rate with no increase in major bleeding compared with standard-dose prophylactic anticoagulation. Also, therapeutic anticoagulation did not provide additional benefit in comparison with high-dose prophylactic anticoagulation. Conclusions On the basis of the common pro-thrombotic pathophysiology described in septic conditions, our work has made it possible to (i) better characterize clinical situations at particularly high thrombotic risk (NOAF, MI, severe COVID-19 infection), (ii) develop individual therapeutic strategies for thrombotic risk prevention (COVID-19), and (iii) establish the basis for subsequent trials in specific intensive care populations at very high thrombotic risk