Medical history of coronary artery disease and time to electrocardiogram in the emergency department: a real-life, single-center, retrospective analysis.

Background: Timely acquisition of 12-lead Electrocardiogram (ECG) in the emergency department (ED) is crucial and recommended by current guidelines.

Objectives: To evaluate the association of medical history of coronary artery disease (hCAD) on door-to-ECG time in the ED.

Methods: In this single center, retrospective cohort study, patients admitted to ED for cardiac evaluation were grouped according to hCAD and no hCAD.

Dual-Pathway Antithrombotic Therapy in Patients With Atrial Fibrillation After Percutaneous Coronary Intervention in Stable Coronary Artery Disease: A Single-Center, Single-Operator, Retrospective Cohort Study.

There is limited data evaluating the prescription practices for antithrombotic therapy in patients with atrial fibrillation (AF) following elective percutaneous coronary intervention (PCI). This single-center, single-operator, retrospective cohort study aimed to evaluate trends of antithrombotic treatment strategies in patients with AF undergoing elective PCI. Patients with AF who electively underwent PCI performed by a single interventionalist between April 2013 and May 2018 were identified.

Extracellular HtrA2 Induces Apoptosis in Human Umbilical Vein Endothelial Cells.

The serine protease high-temperature-required protein A2 (HtrA2) has been identified as a key intracellular molecule promoting apoptosis in cells during ischemia reperfusion (IR) injury. IR injury in ST-segment elevation myocardial infarction (STEMI) contributes to overall myocardial damage. HtrA2 has further been shown to be significantly increased in the serum of patients with STEMI.

Inflammation in acute coronary syndrome: Expression of TLR2 mRNA is increased in platelets of patients with ACS.

Background: Platelets are key components in atherogenesis and determine the course of its clinical sequelae acute coronary syndrome (ACS). Components of the innate immune system-the superfamily of TLR receptors-are present in platelets and represent a link between atherothrombosis and inflammation. We hypothesize that alteration in platelet TLR mRNA expression is a result of inflammation driving coronary atherosclerosis and may represent an alternative platelet activation pathway in ACS.

α-Tocopherol preserves cardiac function by reducing oxidative stress and inflammation in ischemia/reperfusion injury.

Objective: Myocardial infarction (MI) is a leading cause of mortality and morbidity worldwide and new treatment strategies are highly sought-after. Paradoxically, reperfusion of the ischemic myocardium, as achieved with early percutaneous intervention, results in substantial damage to the heart (ischemia/reperfusion injury) caused by cell death due to aggravated inflammatory and oxidative stress responses. Chronic therapy with vitamin E is not effective in reducing the cardiovascular event rate, presumably through failing to reduce atherosclerotic plaque instability.

Digital PCR for Quantifying Circulating MicroRNAs in Acute Myocardial Infarction and Cardiovascular Disease.

Circulating serum microRNAs (miRNAs) have shown promise as biomarkers for the cardiovascular disease and acute myocardial infarction (AMI), being released from the cardiovascular cells into the circulation. Circulating miRNAs are highly stable and can be quantified. The quantitative expression of specific miRNAs can be linked to the pathology, and some miRNAs show high tissue and disease specificity.

Expression of the oxygen-sensitive transcription factor subunit HIF-1α in patients suffering from secondary Raynaud syndrome.

Anti-ischemic therapy remains a challenge due to the complexity of hypoxia response pathways. Hypoxia-inducible factor (HIF)-1 is a heterodimer transcription factor consisting of 2 subunits, HIF-1α and HIF-1β. Hypoxia-dependent activation of HIF-1α regulates cellular O homeostasis.

Chip-based digital PCR as a novel detection method for quantifying microRNAs in acute myocardial infarction patients.

miRNAs have shown promise as potential biomarkers for acute myocardial infarction (AMI). However, the current used quantitative real-time PCR (qRT-PCR) allows solely for relative expression of nucleic acids and it is susceptible to day-to-day variability, which has limited the validity of using the miRNAs as biomarkers. In this study we explored the technical qualities and diagnostic potential of a new technique, chip-based digital PCR, in quantifying the miRNAs in patients with AMI and ischaemia-reperfusion injury (I/R).

The mitochondria-targeting peptide elamipretide diminishes circulating HtrA2 in ST-segment elevation myocardial infarction.

Background: The extent of myocardial damage in patients with ST-segment elevation myocardial infarction (STEMI) depends on both the time to reperfusion as well as injury induced by ischaemia-reperfusion resulting in a cascade of cellular and humoral reactions. As a consequence of ischaemia-reperfusion in the heart, the high-temperature requirement serine peptidase 2 (HtrA2) is translocated from the mitochondria to the cytosol, whereupon it induces protease activity-dependent apoptosis mediated via caspases. Myocardial damage induced by reperfusion cannot be monitored due to a current lack in specific biomarkers.

Direct factor IXa inhibition with the RNA-aptamer pegnivacogin reduces platelet reactivity in vitro and residual platelet aggregation in patients with acute coronary syndromes.

Background: Residual platelet reactivity is a predictor of poor prognosis in patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention. Thrombin is a major platelet activator and upon initiation of the coagulation cascade, it is subsequently produced downstream of factor IXa, which itself is known to be increased in ACS. Pegnivacogin is a novel RNA-aptamer based factor IXa inhibitor featuring a reversal agent, anivamersen.

[Community acquired pneumonia in the emergence department--do standardized care bundles improve quality of care?].

Community acquired pneumonia (CAP) is associated with high in-hospital mortality. The initial correct diagnosis, risk assessment and initiation of treatment are responsibilities of the emergency department (ED). In Germany, emergency medicine is not well established nationwide and organized in a very heterogeneous manner.

Reduction of mortality in community-acquired pneumonia after implementing standardized care bundles in the emergency department.

Objectives: Community-acquired pneumonia (CAP) is associated with high in-hospital mortality. Standardization of diagnostics and adherence to sepsis bundles in the emergency department (ED) are associated with reduced mortality in patients with sepsis. We examined whether introduction of standardized care bundles and checklists in the ED is associated with reduced mortality in patients hospitalized for CAP.

Differential effects of heart rate reduction with ivabradine in two models of endothelial dysfunction and oxidative stress.

Heart rate reduction with the I(f)-channel-inhibitor ivabradine is a novel and appealing option in the therapy of patients with ischemic heart disease. The aim of the current study was to determine the effects of ivabradine in two different animal models of vascular disease characterized by increased oxidative stress and endothelial dysfunction. Wistar rats with angiotensin II induced hypertension and ApoE knockout mice were used as animal models of endothelial dysfunction and oxidative stress, with half of the animals receiving ivabradine 10 mg/kg/day in parallel.

α1AMP-activated protein kinase preserves endothelial function during chronic angiotensin II treatment by limiting Nox2 upregulation.

Objective: Besides its well-described metabolic effects, vascular AMP-activated protein kinase (AMPK) can activate endothelial NO synthase, promotes angiogenesis, and limits endothelial cell apoptosis. The current study was designed to study the effects of α1AMPK deletion during vascular disease in vivo.

Methods And Results: Chronic angiotensin II infusion at low subpressor doses caused a mild endothelial dysfunction that was significantly aggravated in α1AMPK-knockout mice.

[Presence and future of emergency medicine in Germany].

Health care policy has changed duties and responsibilities of hospitals in Germany. The transition zone of in- and outpatient care has been recognized as a critical gateway for the success of hospitals, subsequently leading to the appreciation of the value of professionalized emergency departments. Currently, hospital-based emergency medicine in Germany is organized in a very heterogeneous manner.

Conversion of biliverdin to bilirubin by biliverdin reductase contributes to endothelial cell protection by heme oxygenase-1-evidence for direct and indirect antioxidant actions of bilirubin.

Heme oxygenase-1 (HO-1) is highly protective in various pathophysiological states such as cardiovascular and neurodegenerative diseases. HO-1-derived bilirubin is an efficient scavenger of reactive oxygen and nitrogen species (RONS). It remains to determine whether conversion of biliverdin to bilirubin is an essential step for HO-1-conferred protection of endothelial cells.

Pentaerythritol tetranitrate improves angiotensin II-induced vascular dysfunction via induction of heme oxygenase-1.

The organic nitrate pentaerythritol tetranitrate is devoid of nitrate tolerance, which has been attributed to the induction of the antioxidant enzyme heme oxygenase (HO)-1. With the present study, we tested whether chronic treatment with pentaerythritol tetranitrate can improve angiotensin II-induced vascular oxidative stress and dysfunction. In contrast to isosorbide-5 mononitrate (75 mg/kg per day for 7 days), treatment with pentaerythritol tetranitrate (15 mg/kg per day for 7 days) improved the impaired endothelial and smooth muscle function and normalized vascular and cardiac reactive oxygen species production (mitochondria, NADPH oxidase activity, and uncoupled endothelial NO synthase), as assessed by dihydroethidine staining, lucigenin-enhanced chemiluminescence, and quantification of dihydroethidine oxidation products in angiotensin II (1 mg/kg per day for 7 days)-treated rats.

Manganese superoxide dismutase and aldehyde dehydrogenase deficiency increase mitochondrial oxidative stress and aggravate age-dependent vascular dysfunction.

Aims: Imbalance between pro- and antioxidant species (e.g. during aging) plays a crucial role for vascular function and is associated with oxidative gene regulation and modification.

Cyclooxygenase 2-selective and nonselective nonsteroidal anti-inflammatory drugs induce oxidative stress by up-regulating vascular NADPH oxidases.

Cyclooxygenase 2-selective inhibitors (coxibs) and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increase in cardiovascular events. The current study was designed to test the effect of coxibs and nonselective NSAIDs on vascular superoxide and nitric oxide (NO) production. mRNA expression of endothelial NO synthase (eNOS) and of the vascular NADPH oxidases was studied in spontaneously hypertensive rats (SHR) and in human endothelial cells.

AT1-receptor blockade by telmisartan upregulates GTP-cyclohydrolase I and protects eNOS in diabetic rats.

Several enzymatic sources of reactive oxygen species (ROS) were described as potential reasons of eNOS uncoupling in diabetes mellitus. In the present study, we investigated the effects of AT1-receptor blockade with chronic telmisartan (25 mg/kg/day, 6.5 weeks) therapy on expression of the BH4-synthesizing enzyme GTP-cyclohydrolase I (GCH-I), eNOS uncoupling, and endothelial dysfunction in streptozotocin (STZ, 60 mg/kg iv, 7 weeks)-induced diabetes mellitus (type I).

First evidence for a crosstalk between mitochondrial and NADPH oxidase-derived reactive oxygen species in nitroglycerin-triggered vascular dysfunction.

Chronic nitroglycerin treatment results in development of nitrate tolerance associated with endothelial dysfunction (ED). We sought to clarify how mitochondria- and NADPH oxidase (Nox)-derived reactive oxygen species (ROS) contribute to nitrate tolerance and nitroglycerin-induced ED. Nitrate tolerance was induced by nitroglycerin infusion in male Wistar rats (100 microg/h/4 day) and in C57/Bl6, p47(phox/) and gp91(phox/) mice (50 microg/h/4 day).

Sirolimus-induced vascular dysfunction. Increased mitochondrial and nicotinamide adenosine dinucleotide phosphate oxidase-dependent superoxide production and decreased vascular nitric oxide formation.

Objectives: This study sought to analyze mechanisms that mediate vascular dysfunction induced by sirolimus.

Background: Despite excellent antirestenotic capacity, sirolimus-eluting stents have been found to trigger coronary endothelial dysfunction and impaired re-endothelialization.

Methods: To mimic the continuous sirolimus exposure of a stented vessel, Wistar rats underwent drug infusion with an osmotic pump for 7 days.

Protein kinase C alpha promotes angiogenic activity of human endothelial cells via induction of vascular endothelial growth factor.

Aims: Protein kinase C (PKC) plays an important role in the regulation of angiogenesis. However, downstream targets of PKC in endothelial cells are poorly defined.

Methods And Results: mRNA expression of vascular endothelial growth factor (VEGF) was analysed by quantitative real-time RT-PCR in human umbilical vein endothelial cells (HUVEC) and HUVEC-derived EA.