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.

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

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.

Yes / The silkworm cocoon has been used in the treatment of various ailments in different Asian countries. This research was designed to evaluate the effect of sericin on myocardial necrosis and hypertrophy in isoproterenol-challenged rats. The rats were administered with sericin (500 and 1000 mg/kg, p.o.) for 28 days, followed by administration of isoprenaline (85 mg/kg, s.c.) on the 29th and 30th days. The cardioprotective activity was assessed by various physical, enzymatic, and histopathological parameters along with apoptotic marker expression. The cardioprotective effect showed that pre-treatment of rats with sericin significantly increased the non-enzymatic antioxidants marker in serum and heart tissue (glutathione, vitamin E, and vitamin C). The results were the same in enzymatic antioxidant marker, mitochondrial enzymes, and protein. The grading of heart, heart/body weight ratio, gross morphology, cardiac markers, oxidative stress markers in serum and heart tissue, glucose, serum lipid profiling and Lysosomal hydrolases, heart apoptotic markers such as MHC expression by western blot, apoptosis by flow cytometry, total myocardial collagen content, fibrosis estimation, myocyte size were significantly decreased when compared with isoproterenol (ISG) group however histopathological studies showed normal architecture of heart in both control and treated rats. The pharmacological study reflects that sericin on both doses i.e., 500 mg/kg and 1000 mg/kg have potent cardioprotective action against the experimental model which was confirmed by various physical, biochemical, and histopathological parameters evaluated further research is required to examine the molecular mechanism of cardioprotective effect of sericin. / King Saud University, Riyadh, Saudi Arabia (RSP-2021/357)

Myocardial structure is compromised after myocardial infarction (MI) in vertebrates, resulting in a significant decrease in cardiac output. Pro-proliferative compounds, such as ALK5 inhibitors and p38 inhibitors, are promising in increasing cardiac function after MI, but are only beginning to be functionally evaluated. Zebrafish larvae suffering cardiac arrest in severe acute hypoxia (1 kPa for ~18-20 min) are an effective model for studying how these compounds affect MI. I investigated the effects of ALK5i and p38i on cardiac function after cardiac injury. Several concentrations (0.03 – 100 µmol) administered in four different times of exposure (6, 12, 18, and 24 h) were used. Videos of heartbeat were recorded at three different time points: before hypoxic exposure, 48 h, and 72 h after treatment. For ALK5 inhibition, heart rate (fH) decreased in different groups from 0.03-30 µmol. For p38 inhibition, low concentrations (0.1-1 µmol) during intermediate times increased cardiac function. The concentration 0.3 µmol increased stroke volume by 134%, with no changes in fH. Overall, cardiac output increased significantly (P<0.001) by 144% following p38 inhibition. Behavioral effects caused by a simulated heart attack in 7 dpf zebrafish larvae were tested one and two weeks after simulated heart attack. A control group, a cardiac injury group, and a group with cardiac injury + p38 inhibition (0.3 µmol) were evaluated for anxiety-like behavior and boldness when placed in a novel environment. Larvae with cardiac injury + p38 inhibition spent significantly more time in the thigmotaxis zone compared to larvae with cardiac injury alone, suggesting an increase in anxiety-like behavior (P=0.0395). Boldness was decreased in the cardiac injury group compared to controls, because they spent a shorter time in the novel object zone at two weeks after cardiac arrest (P=0.04). Growth was impaired in both cardiac injury groups, regardless of pharmacological inhibition, with a significant increase in growth compared to controls. Further studies of cardiac function and behavior need to be performed with a holistic approach, to understand the effects of pro-proliferative compounds from molecular to organism level.

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