Myocardial infarction, stroke, and sepsis trigger systemic inflammation and organism-wide complications that are difficult to manage. Here, we examined the contribution of macrophages residing in vital organs to the systemic response after these injuries. We generated a comprehensive catalog of changes in macrophage number, origin, and gene expression in the heart, brain, liver, kidney, and lung of mice with myocardial infarction, stroke, or sepsis. Predominantly fueled by heightened local proliferation, tissue macrophage numbers increased systemically. Macrophages in the same organ responded similarly to different injuries by altering expression of tissue-specific gene sets. Preceding myocardial infarction improved survival of subsequent pneumonia due to enhanced bacterial clearance, which was caused by IFNɣ priming of alveolar macrophages. Conversely, EGF receptor signaling in macrophages exacerbated inflammatory lung injury. Our data suggest that local injury activates macrophages in remote organs and that targeting macrophages could improve resilience against systemic complications following myocardial infarction, stroke, and sepsis. Hoyer, Naxerova, et al. generate a comprehensive catalog of changes in macrophage number, origin, and gene expression in the heart, brain, liver, kidney, and lung of mice with myocardial infarction, stroke, or sepsis. They find that local injury activates macrophages in remote organs and that these adaptations were damaging or protective in different settings.

The Joint Commission in a joint effort with the Centers of Medicare and Medicaid Services (CMS) has established certain "core measures" by which hospital performance is measured. One of these is the measure for patients with ST-elevation myocardial infarction (STEMI) recommending percutaneous coronary intervention within 90 minutes of presentation to the Emergency Department in institutions that are able to provide this service. This recommendation does not take into account the long-term use of clopidogrel that is recommended by the American College of Cardiology and American Heart Association for patients that are treated with coronary stents. The purpose of this study was to evaluate outcomes of providing a short course of clopidogrel versus a prescription alone for clopidogrel to uninsured patients experiencing STEMI who were treated with a bare metal stent. After conducting a cost-benefit analysis, a policy was approved that provided uninsured STEMI patients with clopidogrel at discharge rather than a prescription. A social worker evaluated patients to determine if they met criteria and arranged for medication delivery to the patient’s bedside. A retrospective chart review for all patients who presented to the Emergency Department during two different time frames (before and after policy implementation) was conducted to evaluate if providing clopidogrel decreased readmissions. Data were collected on over a 15-month period of time before and after the clopidogrel policy implementation to allow for evaluation of 90-day readmissions with repeat STEMI. Data were analyzed using chi-square cross tabulation and T-test for independent samples. A total of 201 charts were reviewed: 100 from the pre-intervention group and 101 from the post-intervention group. Demographic characteristics of age, gender and insurance status iv were not statistically different between groups. The mean age for the control group was 59.1 (+ 13.8) years and 58.9 (+ 13.6) years for the intervention group. Twenty percent of the patients were uninsured. Five uninsured patients were readmitted with STEMI prior to the intervention compared to two patients in the intervention group (p = .191). The admissions for the preintervention patients occurred in the first 30 days after discharge compared to 31-60 days in the post-intervention group. All of the patients who were readmitted were assessed to be noncompliant with treatment. Additionally, a transition to increased use of bare metal stents in STEMI patients from 23.1% pre-intervention to 67.4% post-intervention was noted (p < .001). Although no differences were found in readmission rates, fewer readmissions for STEMI were noted after the intervention. The small number of patients who were readmitted with STEMI likely accounted for this finding, and additional monitoring of readmission rates is warranted. Despite provision of the clopidogrel, adherence remains an issue and needs to be addressed. During the intervention, physicians were encouraged to consider the financial and social resources of individual STEMI patients presenting to the Emergency Department to help identify patients that would be less likely to adhere to antiplatelet therapy. In those believed to be at high risk for non-adherence, primarily due to inability to purchase the relatively expensive medication clopidogrel, many physicians chose to insert bare metal stents rather than drugeluting stents to take advantage of the shorter course of clopidogrel required post procedure. Provision of a 30-day course of clopidogrel and aspirin was a major part of this effort to decrease recurrent myocardial infarction in this at-risk population. A few patients eligible for the clopidogrel were not provided the medication if they were admitted to a nursing unit where staff members were not familiar with the policy; revisions to the policy to ensure medication is provided to all eligible patients will be made. Providing clopidogrel to patients who experience v STEMI may improve adherence and thereby decrease readmissions as a result of repeat STEMI due to subacute thrombus formation. Patients who experience STEMI continue to be vulnerable after STEMI. Programs that provide medication to patients should be expanded within this facility and to other hospital systems to encompass all patients who are treated for STEMI. Multi-disciplinary collaboration is necessary in developing and implementing a program that will address care for this.

No description available.

Background: Telomeres are repetitive, gene-poor regions that cap the ends of DNA and help to maintain chromosomal integrity. Their shortening is caused by inflammation and oxidative stress within the cellular environment and ultimately leads to cellular senescence. Shortened leukocyte telomere length (LTL) is hypothesized to be a novel biomarker for age-related diseases and may therefore be useful in the prediction of cardiometabolic outcomes above conventional risk factors. Methods: A systematic review and meta-analysis was undertaken to summarize existing literature on the association between LTL and myocardial infarction (MI), stroke, and type 2 diabetes (T2D). MEDLINE (1966–present), and EMBASE (1980-present) were last searched on September 9th 2013. Studies were combined using the generic inverse variance method and both fixed and random effects models. Additionally, LTL was measured in 3972 MI patients and 4321 controls from an international study on risk factors for MI (INTERHEART), and 8635 participants from an epidemiological study on dysglycemia and T2D (EpiDREAM) prospectively followed (approximately 3.5 years) for incident cardiometabolic events. Results: Based on current literature, a 1-standard deviation decrease in LTL was significantly associated with stroke (OR=1.21, 95% CI=1.06-1.37; I2=61%), myocardial infarction (OR=1.24, 95% CI=1.04-1.47; I2=68%), and type 2 diabetes (OR=1.37, 95% CI=1.10-1.72; I2=91%). Stratification by measurement technique, study design, study size, and ethnicity explained heterogeneity in certain cardiometabolic outcomes. Within INTERHEART participants, a 1 unit decrease in LTL was associated with an increased risk of MI (OR=2.17, 95% CI=1.74-2.72). Effect estimates were consistent across all ethnic groups (p=0.19). In EpiDREAM a significant association between LTL and T2D or incident cardiometabolic outcomes was not observed. Conclusion: Telomere length appears to be a marker for MI above conventional risk factors. Further research is needed to explain existing heterogeneity in the literature with respect to LTL and T2D. / Thesis / Master of Science (MSc)

Otolin-1 is a collagenous, C1q domain-containing extracellular matrix protein that has been identified and characterized in the inner ear. Recently, mass spectrometry analysis of left ventricular cardiac tissue detected a peptide of Otolin-1. Experimental analysis confirms Otolin-1 is an insoluble protein present in the left ventricular extracellular matrix whose expression decreases dramatically post-myocardial infarction beginning at day 5 post-MI. The protein is localized to the gap junctions of cardiac myocytes, and depletion of protein levels in the infarcted region of the left ventricle shows strong association with ventricular dimensions, observed via echocardiography.

No / Myocardial infarction (MI) is an acute life-threatening disease with a high incidence worldwide. Aim of this study was to test lectin-carbohydrate binding-induced red blood cell (RBC) agglutination as an innovative tool for fast, precise and cost effective diagnosis of MI. Five lectins (Ricinus communis agglutinin (RCA), Phaseolus vulgaris erythroagglutinin (PHA), Datura stramonium agglutinin (DSA), Artocarpus agglutinin (ArA), Triticum agglutinin (TA)) were tested for ability to differentiate between agglutination characteristics in patients with MI (n = 101) or angina pectoris without MI (AP) (n = 34) and healthy volunteers (HV) as control (n =68) . RBC agglutination was analyzed by light absorbance of a stirred RBC suspension in the green to red light spectrum in an agglutimeter (amtec, Leipzig, Germany) for 15 min after lectin addition. Mean cell count in aggregates was estimated from light absorbance by a mathematical model. Each lectin induced RBC agglutination. RCA led to the strongest RBC agglutination (~500 RBCs/aggregate), while the others induced substantially slower agglutination and lead to smaller aggregate sizes (5-150 RBCs/aggregate). For all analyzed lectins the lectin-induced RBC agglutination of MI or AP patients was generally higher than for HV. However, only PHA induced agglutination that clearly distinguished MI from HV. Variance analysis showed that aggregate size after 15 min. agglutination induced by PHA was significantly higher in the MI group (143 RBCs/ aggregate) than in the HV (29 RBC-s/aggregate, p = 0.000). We hypothesize that pathological changes during MI induce modification of the carbohydrate composition on the RBC membrane and thus modify RBC agglutination. Occurrence of carbohydrate-lectin binding sites on RBC membranes provides evidence about MI. Due to significant difference in the rate of agglutination between MI > HV the differentiation between these groups is possible based on PHA-induced RBC-agglutination. This novel assay could serve as a rapid, cost effective valuable new tool for diagnosis of MI.

京都大学 / 新制・論文博士 / 博士(社会健康医学) / 乙第13637号 / 論社医博第20号 / 新制||社医||13(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 石見 拓, 教授 大鶴 繁, 教授 尾野 亘 / 学位規則第4条第2項該当 / Doctor of Public Health / Kyoto University / DFAM

published_or_final_version / abstract / Community Medicine / Doctoral / Doctor of Philosophy

<p>Myocardial infarction (MI) causes high morbidity and mortality worldwide and for effective prevention and treatment MIs have to be adequately detected. </p><p>The existence of clinically unrecognized MIs (UMIs) has been known for the past hundred years, but an ultimate tool for their detection has not yet been found. Using persistent Q waves on electrocardiography as a sign of MI, it has been estimated that UMIs constitute at least ¼ of all MIs and have mortality rates similar to those of recognized MIs (RMIs). These estimates are misleading, however, since persistent Q waves do not necessarily represent MIs.</p><p>The late enhancement technique in magnetic resonance imaging (LE MRI) has been developed over the past decade and accurately determines myocardial viability. The aim of this research was to investigate the prevalence and impact of UMI and RMI in a population-based sample of 70-year-olds, assessed with MRI.</p><p>Cardiac function and viability were examined with MRI in 259 randomly selected 70-year-old subjects (127 women, 132 men) participating in a larger population-based study (PIVUS). Information on other parameters of cardiovascular disease was obtained and related to the findings.</p><p>Three methods for segmentation of the left ventricular mass were used in the first 100 subjects; these differed in accuracy and led to differences in systolic function values. In the subsequent 159 examinations one of the segmentation methods was used. </p><p>The viability images were assessable in 248 subjects (123 women, 125 men). Among these, the prevalence of UMI, 19.8%, definitely exceeded the expectations and UMIs constituted 4/5 of all MIs. The prevalence of RMI was 4.4%. MRI-detected UMIs differed from RMIs in several respects; they were smaller, frequently located inferolaterally, did not appear to be associated with atherosclerosis, and displayed increased collagen turnover. The pathogenesis of these UMIs remains to be investigated, but our observations suggest that they are caused by ischemia. Subjects with UMI showed increased cardiac morbidity, a decreased ejection fraction and an increased left ventricular mass, indicating an increased cardiovascular risk.</p><p>It is thus important to detect these UMIs, and this is adequately achieved by LE MRI. However, to decide upon prevention and treatment of these UMIs we need to know more about their pathogenesis and prognosis.</p>

Myocardial infarction (MI) causes high morbidity and mortality worldwide and for effective prevention and treatment MIs have to be adequately detected. The existence of clinically unrecognized MIs (UMIs) has been known for the past hundred years, but an ultimate tool for their detection has not yet been found. Using persistent Q waves on electrocardiography as a sign of MI, it has been estimated that UMIs constitute at least ¼ of all MIs and have mortality rates similar to those of recognized MIs (RMIs). These estimates are misleading, however, since persistent Q waves do not necessarily represent MIs. The late enhancement technique in magnetic resonance imaging (LE MRI) has been developed over the past decade and accurately determines myocardial viability. The aim of this research was to investigate the prevalence and impact of UMI and RMI in a population-based sample of 70-year-olds, assessed with MRI. Cardiac function and viability were examined with MRI in 259 randomly selected 70-year-old subjects (127 women, 132 men) participating in a larger population-based study (PIVUS). Information on other parameters of cardiovascular disease was obtained and related to the findings. Three methods for segmentation of the left ventricular mass were used in the first 100 subjects; these differed in accuracy and led to differences in systolic function values. In the subsequent 159 examinations one of the segmentation methods was used. The viability images were assessable in 248 subjects (123 women, 125 men). Among these, the prevalence of UMI, 19.8%, definitely exceeded the expectations and UMIs constituted 4/5 of all MIs. The prevalence of RMI was 4.4%. MRI-detected UMIs differed from RMIs in several respects; they were smaller, frequently located inferolaterally, did not appear to be associated with atherosclerosis, and displayed increased collagen turnover. The pathogenesis of these UMIs remains to be investigated, but our observations suggest that they are caused by ischemia. Subjects with UMI showed increased cardiac morbidity, a decreased ejection fraction and an increased left ventricular mass, indicating an increased cardiovascular risk. It is thus important to detect these UMIs, and this is adequately achieved by LE MRI. However, to decide upon prevention and treatment of these UMIs we need to know more about their pathogenesis and prognosis.