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Find video protocols related to scientific articles indexed in Pubmed.
Preoperative interleukin-22 values add valuable information for outcome prediction following orthotopic liver transplantation: a preliminary study.
Ann. Transplant.
PUBLISHED: 10-11-2014
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Recent findings support the idea that interleukin (IL)-22 serum levels are related to disease severity in end-stage liver disease. Existing scoring systems--Model for End-Stage Liver Disease (MELD), Survival Outcomes Following Liver Transplantation (SOFT) and Pre-allocation-SOFT (P-SOFT)--are well-established in appraising survival rates with or without liver transplantation. We tested the hypothesis that IL-22 serum levels at transplantation date correlate with survival and potentially have value as a predictive factor for survival.
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Aggregometric assessment of clonidine's impact on the efficacy of dual platelet inhibition.
Clin. Lab.
PUBLISHED: 10-09-2014
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Clonidine is commonly used as a calmative and antihypertensive agent in perioperative care. Due to the drug's alpha-2-agonistic effects, it has recently been hypothesised that clonidine may affect platelet aggregability. The present investigation aimed to study the potential impact of clonidine on the efficacy of dual antiplatelet therapy.
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Complications associated with the prehospital use of laryngeal tubes-A systematic analysis of risk factors and strategies for prevention.
Resuscitation
PUBLISHED: 08-07-2014
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With the increasing spread of laryngeal tubes (LT) in emergency medicine, complications and side-effects are observed. We sought to identify complications associated with the use of LTs in emergency medicine, and to develop strategies to prevent these incidents.
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Use of lidocaine in endotracheal intubation. Blood and urine concentrations in patients and deceased after unsuccessful resuscitation.
Forensic Sci. Int.
PUBLISHED: 08-04-2014
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In toxicological analysis of postmortem samples the local anesthetic lidocaine is often identified. In most cases, lidocaine levels result from its use as aid in endotracheal intubation. The range of the drug's concentration in blood and urine was studied under controlled conditions from a cohort of cardiac surgery patients (n=35). Plasma concentrations 1h after exposure to lidocaine in the range of the recommended 81mg coating the endotracheal tube were less than 0.2mg/l, its metabolite monoethylglycinxylidide (MEGX) less than 0.05mg/l (median ratio 0.18, range 0.03-1.23). Also the concentrations of lidocaine and MEGX in urine samples were low (less than 1.2 and 0.1mg/l, respectively) with MEGX/lidocaine ratios of 0.11 (median, range up to 1.2). These data were compared with results obtained by analyzing postmortem blood and urine samples of 18 deceased with a documented cardiopulmonary resuscitation attempt prior to death. Blood concentrations were in the same range (lidocaine median 0.07, range 0.02-1.07mg/l; MEGX median 0.01, range <0.001-0.044mg/l); besides low lidocaine concentrations in urine. MEGX was detected only in 2 out of 9 urine samples. The results of the present study confirm that lidocaine is absorbed in the trachea from the endotracheal tube coated with lidocaine containing gel. Postmortem quantitative results can be explained on the basis of the data obtained in the controlled study.
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Multiple Electrode Aggregometry for the Assessment of Acquired Platelet Dysfunctions during Extracorporeal Circulation.
Thorac Cardiovasc Surg
PUBLISHED: 08-01-2014
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Background?There have been many reports on how the usage of extracorporeal circulation (ECC) is independently associated with the induction of platelet dysfunctions. The aim of the present investigation was to study the capability of the multiple electrode aggregometry (MEA) using the Multiplate (Roche AG, Grenzach, Germany) device to reflect the extent of ECC-associated platelet dysfunctions. Patients and Methods?The study population consisted of patients who were treated with either hypothermic (cardiopulmonary bypass [CPB]) or normothermic (extracorporeal membrane oxygenation) ECC. Hemostatic analyses included conventional laboratory coagulation tests and aggregometric measures following stimulation with different agonists using MEA. The area under the aggregation curve in the ADPtest (ex vivo adenosine diphosphate induced platelet aggregation) of the MEA was defined as the primary end point. The analyses were performed before the usage of ECC (baseline) and 90 minutes (T1), 120 minutes (T2), 150 minutes (T3), and 180 minutes (T4) after the usage of ECC. In the hypothermic ECC group, additional hemostatic analyses were performed after the patient's postoperative admission to the intensive care unit (T5). Periprocedural data and results of other hemostatic testing were defined as secondary end points. Results?A total of n?=?40 patients were assessed for eligibility and n?=?25 patients were finally enrolled into the study (hypothermic ECC group: n?=?20; normothermic ECC group: n?=?5). The extent of ADP-induced platelet aggregation decreased significantly between baseline and consecutive measuring points during hypothermic ECC and remained unchanged between T4 and T5. In the normothermic ECC group, ADP-induced aggregability was significantly lower at T1 compared with baseline and remained unchanged from T1 onward. Conclusion?Data from the present study indicate that ex vivo ADP-induced platelet aggregation in MEA reflects the time-dependent extent of ECC-induced platelet dysfunction.
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Hemotherapy algorithms for coagulopathic cardiac surgery patients.
Clin. Lab.
PUBLISHED: 07-15-2014
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In patients undergoing cardiac surgery, perioperative coagulopathy and the use of allogenic blood products are independently associated with increased mortality and major perioperative cardiac and non-cardiac adverse events. Hemotherapy should be based on specific hemotherapy algorithms rather than "clinical judgments". However, whether hemotherapy should be based on "classical" conventional laboratory coagulation analyses or Point-of-Care (POC) measures is discussed controversially. There is very good evidence from retrospective studies and prospective randomized controlled trials that the implementation of viscoelastic and aggregometric measurements in hemostatic therapy algorithms may reduce the transfusion rate of allogenic blood products. Furthermore, data suggest improved clinical outcome. Unfortunately, the studied hemotherapy--algorithms are very complex and thus hard to integrate into daily practice. In close cooperation of three German University Hospitals, the authors developed and implemented two more comprehensive and practical hemotherapy algorithms that are based on either POC measures or conventional coagulation testing. Here we present and discuss the structure and limitations of these algorithms.
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[Hemorrhage after accidental overdosage of enoxaparin: monitoring and therapy].
Anasthesiol Intensivmed Notfallmed Schmerzther
PUBLISHED: 07-08-2014
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At the morning of the sixth postoperative day after a complex cardiac surgery procedure, a patient accidentally received a subcutaneous injection of 450 mg Enoxaparin sodium (Clexane®, Sanofi GmbH, Frankfurt, Germany). A few hours later an excessive coagulopathy developed and necessitated the transfusion of allogenic blood products. The present case report describes and discusses our diagnostic and therapeutic approaches.
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Savoring every drop - Vampire or Mosquito?
Crit Care
PUBLISHED: 05-21-2014
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Blood safety with respect to infectious complications has reached very high standards. Nevertheless, reports on transfusion-associated morbidity and mortality gain momentum. Multidisciplinary patient blood management programs can minimize unnecessary exposure to allogeneic blood products by strengthening and conserving patients' own resources. This article outlines concepts designed to maintain hemoglobin concentration, to optimize hemostasis, and to minimize blood loss in ICUs. These measures prevent or at least alleviate hospital-acquired anemia, reduce the need for blood transfusions, and therefore have great potential to improve patient safety and medical outcome.
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What's new in volume therapy in the intensive care unit?
Best Pract Res Clin Anaesthesiol
PUBLISHED: 05-06-2014
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The administration of intravenous fluid to critically ill patients is one of the most common but also one of the most fiercely debated interventions in intensive care medicine. During the past decade, a number of important studies have been published which provide clinicians with improved knowledge regarding the timing, the type and the amount of fluid they should give to their critically ill patients. However, despite the fact that many thousands of patients have been enrolled in these trials of alternative fluid strategies, consensus remains elusive and practice is widely variable. Early adequate resuscitation of patients in shock followed by a restrictive strategy may be associated with better outcomes. Colloids such as modern hydroxyethyl starch are more effective than crystalloids in early resuscitation of patients in shock, and are safe when administered during surgery. However, these colloids may not be beneficial later in the course of intensive care treatment and should best be avoided in intensive care patients who have a high risk of developing acute kidney injury. Albumin has no clear benefit over saline and is associated with increased mortality in neurotrauma patients. Balanced fluids reduce the risk of hyperchloraemic acidosis and possibly kidney injury. The use of hypertonic fluids in patients with sepsis and acute lung injury warrants further investigation and should be considered experimental at this stage. Fluid therapy impacts relevant patient-related outcomes. Clinicians should adopt an individualized strategy based on the clinical scenario and best available evidence. One size does not fit all.
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[Patient blood management--How does it work in practice?--the interdisciplinary cooperation].
Anasthesiol Intensivmed Notfallmed Schmerzther
PUBLISHED: 05-02-2014
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Patient blood management (PBM), as a multidisciplinary, evidence-based treatment concept for reducing anemia and blood losses, should be realized in individual hospitals after local adaptation according to the available facilities.The implementation of a PBM program in clinical institutions will be a challenging but in every case worthwhile task. The local facilities may be insufficient to fulfill the training requirements of a large group of different personnel. Accordingly, sustained support by the hospital's management with provision of the necessary resources for personnel and materials is essential. The formation of the core PBM team, in our case consisting initially of anaesthesiologists, surgeons, internists and transfusion medicine specialists as well as - the particularly important - motivated nursing personnel, is one of the most pressing and primary tasks in the establishment of a PBM project.It is also extremely important to firmly anchor the PBM project permanently within the hospital. Possible steps and details for this purpose are presented and discussed in terms of value and weighting by the authors on the basis of their actual experience in Frankfurt University Hospital.
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VEGF-A blockade reduces reperfusion edema but favors arterial thromboembolism in a rat model of orthotopic lung transplantation.
Transplantation
PUBLISHED: 04-11-2014
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Ischemia-reperfusion edema is a common early complication after lung transplantation where the hypoxia-induced vascular endothelial growth factor (VEGF)-A plays a pivotal role. It remains unclear whether a VEGF blockade is beneficial in lung transplantation.
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Activities of cardiac tissue matrix metalloproteinases 2 and 9 are reduced by remote ischemic preconditioning in cardiosurgical patients with cardiopulmonary bypass.
J Transl Med
PUBLISHED: 02-07-2014
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Transient episodes of ischemia in a remote organ or tissue (remote ischemic preconditioning, RIPC) can attenuate myocardial injury. Myocardial damage is associated with tissue remodeling and the matrix metalloproteinases 2 and 9 (MMP-2/9) are crucially involved in these events. Here we investigated the effects of RIPC on the activities of heart tissue MMP-2/9 and their correlation with serum concentrations of cardiac troponin T (cTnT), a marker for myocardial damage.
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Comparison of the TruView infant EVO2 PCD™ and C-MAC video laryngoscopes with direct Macintosh laryngoscopy for routine tracheal intubation in infants with normal airways.
Clinics (Sao Paulo)
PUBLISHED: 01-30-2014
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Videolaryngoscopy has mainly been developed to facilitate difficult airway intubation. However, there is a lack of studies demonstrating this method's efficacy in pediatric patients. The aim of the present study was to compare the TruView infant EVO2 and the C-MAC videolaryngoscope with conventional direct Macintosh laryngoscopy in children with a bodyweight ?10 kg in terms of intubation conditions and the time to intubation.
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The early activation of toll-like receptor (TLR)-3 initiates kidney injury after ischemia and reperfusion.
PLoS ONE
PUBLISHED: 01-01-2014
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Acute kidney injury (AKI) is one of the most important complications in hospitalized patients and its pathomechanisms are not completely elucidated. We hypothesize that signaling via toll-like receptor (TLR)-3, a receptor that is activated upon binding of double-stranded nucleotides, might play a crucial role in the pathogenesis of AKI following ischemia and reperfusion (IR). Male adult C57Bl6 wild-type (wt) mice and TLR-3 knock-out (-/-) mice were subjected to 30 minutes bilateral selective clamping of the renal artery followed by reperfusion for 30 min 2.5h and 23.5 hours or subjected to sham procedures. TLR-3 down-stream signaling was activated already within 3 h of ischemia and reperfusion in post-ischemic kidneys of wt mice lead to impaired blood perfusion followed by a strong pro-inflammatory response with significant neutrophil invasion. In contrast, this effect was absent in TLR-3-/- mice. Moreover, the quick TLR-3 activation resulted in kidney damage that was histomorphologically associated with significantly increased apoptosis and necrosis rates in renal tubules of wt mice. This finding was confirmed by increased kidney injury marker NGAL in wt mice and a better preserved renal perfusion after IR in TLR-3-/- mice than wt mice. Overall, the absence of TLR-3 is associated with lower cumulative kidney damage and maintained renal blood perfusion within the first 24 hours of reperfusion. Thus, we conclude that TLR-3 seems to participate in the pathogenesis of early acute kidney injury.
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The small fibrinopeptide B?15-42 as renoprotective agent preserving the endothelial and vascular integrity in early ischemia reperfusion injury in the mouse kidney.
PLoS ONE
PUBLISHED: 01-01-2014
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Disruption of the renal endothelial integrity is pivotal for the development of a vascular leak, tissue edema and consequently acute kidney injury. Kidney ischemia amplifies endothelial activation and up-regulation of pro-inflammatory mechanisms. After restoring a sufficient blood flow, the kidney is damaged through complex pathomechanisms that are classically referred to as ischemia and reperfusion injury, where the disruption of the inter-endothelial connections seems to be a crucial step in this pathomechanism. Focusing on the molecular cell-cell interaction, the fibrinopeptide B?15-42 prevents vascular leakage by stabilizing these inter-endothelial junctions. The peptide associates with vascular endothelial-cadherin, thus preventing early kidney dysfunction by preserving blood perfusion efficacy, edema formation and thus organ dysfunction. We intended to demonstrate the early therapeutic benefit of intravenously administered B?15-42 in a mouse model of renal ischemia and reperfusion. After 30 minutes of ischemia, the fibrinopeptide B?15-42 was administered intravenously before reperfusion was commenced for 1 and 3 hours. We show that B?15-42 alleviates early functional and morphological kidney damage as soon as 1 h and 3 h after ischemia and reperfusion. Mice treated with B?15-42 displayed a significantly reduced loss of VE-cadherin, indicating a conserved endothelial barrier leading to less neutrophil infiltration which in turn resulted in significantly reduced structural renal damage. The significant reduction in tissue and serum neutrophil gelatinase-associated lipocalin levels reinforced our findings. Moreover, renal perfusion analysis by color duplex sonography revealed that B?15-42 treatment preserved resistive indices and even improved blood velocity. Our data demonstrate the efficacy of early therapeutic intervention using the fibrinopeptide B?15-42 in the treatment of acute kidney injury resulting from ischemia and reperfusion. In this context B?15-42 may act as a potent renoprotective agent by preserving the endothelial and vascular integrity.
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Attenuation of Myocardial Injury by HMGB1 Blockade during Ischemia/Reperfusion Is Toll-Like Receptor 2-Dependent.
Mediators Inflamm.
PUBLISHED: 08-29-2013
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Genetic or pharmacological ablation of toll-like receptor 2 (TLR2) protects against myocardial ischemia/reperfusion injury (MI/R). However, the endogenous ligand responsible for TLR2 activation has not yet been detected. The objective of this study was to identify HMGB1 as an activator of TLR2 signalling during MI/R. C57BL/6 wild-type (WT) or TLR2(-/-)-mice were injected with vehicle, HMGB1, or HMGB1 BoxA one hour before myocardial ischemia (30?min) and reperfusion (24?hrs). Infarct size, cardiac troponin T, leukocyte infiltration, HMGB1 release, TLR4-, TLR9-, and RAGE-expression were quantified. HMGB1 plasma levels were measured in patients undergoing coronary artery bypass graft (CABG) surgery. HMGB1 antagonist BoxA reduced cardiomyocyte necrosis during MI/R in WT mice, accompanied by reduced leukocyte infiltration. Injection of HMGB1 did, however, not increase infarct size in WT animals. In TLR2(-/-)-hearts, neither BoxA nor HMGB1 affected infarct size. No differences in RAGE and TLR9 expression could be detected, while TLR2(-/-)-mice display increased TLR4 and HMGB1 expression. Plasma levels of HMGB1 were increased MI/R in TLR2(-/-)-mice after CABG surgery in patients carrying a TLR2 polymorphism (Arg753Gln). We here provide evidence that absence of TLR2 signalling abrogates infarct-sparing effects of HMGB1 blockade.
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Hypothalamo-pituitary and immune-dependent adrenal regulation during systemic inflammation.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 08-19-2013
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Inflammation-related dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is central to the course of systemic inflammatory response syndrome or sepsis. The underlying mechanisms, however, are not well understood. Initial activation of adrenocortical hormone production during early sepsis depends on the stimulation of hypothalamus and pituitary mediated by cytokines; in late sepsis, there is a shift from neuroendocrine to local immune-adrenal regulation of glucocorticoid production. Therefore, the modulation of the local immune-adrenal cross talk, and not of the neuroendocrine circuits involved in adrenocorticotropic hormone production, may be more promising in the prevention of the adrenal insufficiency associated with prolonged sepsis. In the present work, we investigated the function of the crucial Toll-like receptor (TLR) adaptor protein myeloid differentiation factor 88 (MyD88) in systemic and local activation of adrenal gland inflammation and glucocorticoid production mediated by lipopolysachharides (LPSs). To this end, we used mice with a conditional MyD88 allele. These mice either were interbred with Mx1 Cre mice, resulting in systemic MyD88 deletion, predominantly in the liver and hematopoietic system, or were crossed with Akr1b7 Cre transgenic mice, resulting thereby in deletion of MyD88, which was adrenocortical-specific. Although reduced adrenal inflammation and HPA-axis activation mediated by LPS were found in Mx1(Cre+)-MyD88(fl/fl) mice, adrenocortical-specific MyD88 deletion did not alter the adrenal inflammation or HPA-axis activity under systemic inflammatory response syndrome conditions. Thus, our data suggest an important role of immune cell rather than adrenocortical MyD88 for adrenal inflammation and HPA-axis activation mediated by LPS.
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Perioperative coagulation management during cardiac surgery.
Curr Opin Anaesthesiol
PUBLISHED: 06-29-2013
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Cardiac surgery patients commonly present bleeding complications that negatively influence patients clinical outcome. Therefore, fast and detailed diagnoses as well as early and specific therapy of perioperative coagulopathy are of high clinical relevance. The so-called point-of-care (POC) methods for coagulation analyses are increasingly used in perioperative care. It is the purpose of this review to present modern aspects of coagulation management, discuss the effect of the implementation of POC methods in perioperative care, and present substantial components of hemotherapy algorithms to manage coagulopathy in cardiac surgery patients.
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[Perioperative point-of-care coagulation testing--recently published studies].
Anasthesiol Intensivmed Notfallmed Schmerzther
PUBLISHED: 06-11-2013
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Point-of-care (POC) devices are increasingly being used at the bedside in perioperative patient management of hemostatic function. Aggregometric methods can be utilized in preoperative screening of thrombocytopathia and are qualified to describe the efficacy of antiplatelet therapy. Published data about the value of point-of-care diagnostic gives partially conflicting results.Current prospective randomized studies indicate that implementation of hemostatic treatment algorithms based on viscoelastic and aggregometric POC-analysis may reduce transfusion rate of allogenic blood products, improve clinical outcome and reduce cost of hemostatic treatment.
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[Management of extended blood loss and massive transfusion].
Anasthesiol Intensivmed Notfallmed Schmerzther
PUBLISHED: 06-11-2013
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In patients suffering from massive bleeding, transfusion of allogenic blood products (red blood cells, fresh frozen plasma and platelets) and the application of other hemostatic therapy in form of coagulation factor concentrates represent therapeutic approaches to optimize hemostasis and to restore and assure tissue oxygenation. In accordance to the "Helsinki declaration on patient safety" of the European Society of Anaesthesiology, this review article describes a clinical practice guideline for the treatment of patients requiring massive transfusion that was implemented at the University hospital Frankfurt in 2013. Our guideline may be used as a template for other institutions.
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TLR2 stimulation induces cardiac inflammation but not cardiac depression in vivo.
J Inflamm (Lond)
PUBLISHED: 05-16-2013
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Bacteria such as Staphylococcus aureus induce myocardial dysfunction in vivo. To rectify conflicting evidence about the role of TLR2 signaling and cardiac dysfunction, we hypothesized that the specific TLR2 agonist purified lipoteichoic acid (LTA) from S. aureus contributes to cardiac dysfunction in vitro and in vivo.
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Systemic endotoxin activity correlates with clot formation: an observational study in patients with early systemic inflammation and sepsis.
Crit Care
PUBLISHED: 04-12-2013
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Inflammation and coagulation are closely linked, and both can be triggered by endotoxin. Thrombelastometry and impedance aggregometry are of diagnostic and predictive value in critically ill patients. In this observational study we investigated the correlation of endotoxin activity with thrombelasometric and aggregometric variables in patients with systemic inflammation.
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The NFKB1 promoter polymorphism (-94ins/delATTG) alters nuclear translocation of NF-?B1 in monocytes after lipopolysaccharide stimulation and is associated with increased mortality in sepsis.
Anesthesiology
PUBLISHED: 02-26-2013
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Because the nuclear factor-?B (NF-?B) coupled pathway is believed to amplify inflammation prevailing in sepsis, the authors tested the hypotheses that the insertion-deletion polymorphism (-94ins/delATTG) (1) alters nuclear translocation of nuclear factor-?B and activator protein-1 (NF-?B1) in monocytes after lipopolysaccharide stimulation; (2) affects lipopolysaccharide-induced NF-?B1 messenger RNA expression, tumor necrosis factor ? concentrations, and tissue factor activity; and (3) may be associated with increased 30-day mortality in patients with sepsis.
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Determination of organ-specific anemia tolerance.
Crit. Care Med.
PUBLISHED: 02-07-2013
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Utilization of anemia tolerance reduces the need for and risks of perioperative transfusion. Recent publications indicate that the critical limit for oxygen supply might not be the same for each organ system. Therefore, we investigated the effects of acute dilutional anemia on heart, brain, kidneys, liver, small intestine, and skeletal muscle to quantify organ-specific tolerance of different levels of acute anemic hypoxia. We hypothesized that, in some organs, tissue hypoxia occurs before the critical limits of systemic oxygen supply are reached.
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Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury.
Crit Care
PUBLISHED: 01-16-2013
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INTRODUCTION: Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. METHODS: We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. RESULTS: Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. CONCLUSIONS: Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. TRIAL REGISTRATION: ClinicalTrials.gov number NCT01209169.
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Aprotinin may increase mortality in low and intermediate risk but not in high risk cardiac surgical patients compared to tranexamic acid and ?-aminocaproic acid -- a meta-analysis of randomised and observational trials of over 30.000 patients.
PLoS ONE
PUBLISHED: 01-05-2013
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To compare the effect of aprotinin with the effect of lysine analogues (tranexamic acid and ?-aminocaproic acid) on early mortality in three subgroups of patients: low, intermediate and high risk of cardiac surgery.
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Characterization of the LPS-induced inflammation of the adrenal gland in mice.
Mol. Cell. Endocrinol.
PUBLISHED: 01-05-2013
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Systemic administration of endotoxin, which closely mimics the bacteria-induced systemic inflammatory response syndrome (SIRS) can ultimately lead to organ failure. Adrenal gland insufficiency is frequently diagnosed in critically ill patients; however, the underlying mechanisms are still unclear. In the present study, we studied comprehensively the characteristics of adrenal gland dysregulation, including inflammation, leukocyte infiltration and cell death in the adrenal glands in the course of LPS-induced systemic inflammation in mice. LPS enhanced expression of many proinflammatory cytokines, chemokines and adhesion molecules, which resulted in rapid recruitment of leukocytes into the adrenal gland. Furthermore, LPS-mediated inflammation was associated with increased apoptosis of adrenocortical and chromaffin cells. Our results performed in mice, suggest that LPS-induced adrenal gland inflammation and cell death might be mechanisms potentially involved in the adrenal gland dysfunction in patients with sepsis.
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Prednisolone as preservation additive prevents from ischemia reperfusion injury in a rat model of orthotopic lung transplantation.
PLoS ONE
PUBLISHED: 01-01-2013
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The lung is, more than other solid organs, susceptible for ischemia reperfusion injury after orthotopic transplantation. Corticosteroids are known to potently suppress pro-inflammatory processes when given in the post-operative setting or during rejection episodes. Whereas their use has been approved for these clinical indications, there is no study investigating its potential as a preservation additive in preventing vascular damage already in the phase of ischemia. To investigate these effects we performed orthotopic lung transplantations (LTX) in the rat. Prednisolone was either added to the perfusion solution for lung preservation or omitted and rats were followed for 48 hours after LTX. Prednisolone preconditioning significantly increased survival and diminished reperfusion edema. Hypoxia induced vasoactive cytokines such as VEGF were reduced. Markers of leukocyte invasiveness like matrix metalloprotease (MMP)-2, or common pro-inflammatory molecules like the CXCR4 receptor or the chemokine (C-C motif) ligand (CCL)-2 were downregulated by prednisolone. Neutrophil recruitment to the grafts was only increased in Perfadex treated lungs. Together with this, prednisolone treated animals displayed significantly reduced lung protein levels of neutrophil chemoattractants like CINC-1, CINC-2?/? and LIX and upregulated tissue inhibitor of matrix metalloproteinase (TIMP)-1. Interestingly, lung macrophage invasion was increased in both, Perfadex and prednisolone treated grafts, as measured by MMP-12 or RM4. Markers of anti-inflammatory macrophage transdifferentiation like MRC-1, IL-13, IL-4 and CD163, significantly correlated with prednisolone treatment. These observations lead to the conclusion that prednisolone as an additive to the perfusion solution protects from hypoxia triggered danger signals already in the phase of ischemia and thus reduces graft edema in the phase of reperfusion. Additionally, prednisolone preconditioning might also lead to macrophage polarization as a beneficial long-term effect.
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Postoperative neurocognitive dysfunction in patients undergoing cardiac surgery after remote ischemic preconditioning: a double-blind randomized controlled pilot study.
PLoS ONE
PUBLISHED: 01-01-2013
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Remote ischemic preconditioning (RIPC) has been shown to enhance the tolerance of remote organs to cope with a subsequent ischemic event. We hypothesized that RIPC reduces postoperative neurocognitive dysfunction (POCD) in patients undergoing complex cardiac surgery.
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Measure for measure-determination of infarct size in murine models of myocardial ischemia and reperfusion: a systematic review.
Shock
PUBLISHED: 10-01-2011
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Myocardial ischemia/reperfusion injury (MI/R) is one of the most prominent topics of contemporary research. The frequent failure of potential therapeutic drugs and interventions to transfer to clinical practice demonstrates the limitations in using experimental animal models. Because a variety of transgenic animals are readily available in mice, researchers in recent years have made use of murine models rather than of larger animal models for experimental MI/R. This review focuses on in vivo and ex vivo murine models of MI/R and aims to characterize the source of our mechanistic understanding in mice. A systematic review of the literature demonstrated that there is great diversity among ex vivo (Langendorff) and in vivo models of MI/R.
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Low hemoglobin levels during normovolemia are associated with electrocardiographic changes in pigs.
Shock
PUBLISHED: 08-04-2011
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We studied whether low hemoglobin concentrations during normovolemia change the myocardial electrical current (electrocardiogram) in a pig model. Normovolemic anemia was achieved by stepwise replacing blood with colloids (hydroxyethyl starch 6%). We measured the length of the PQ-, QT-, QTc, and the ST interval as well as the amplitude of the Q wave and T wave at hemoglobin concentrations of 9.5, 8.0, 5.5, 3.8, and 3.3 g·dL. Normovolemic anemia is accompanied by a gradual prolongation of the QT and QTc interval and a reduction in the amplitude of the T wave. The QRS complex is partly diminished in amplitude. Results were verified performing a time-frequency analysis on single heartbeats. During severe anemia and normovolemia, electrocardiographic changes can be detected. Further investigations are warranted to elucidate whether these changes indicate myocardial hypoxia.
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Efficacy of the EZ-IO needle driver for out-of-hospital intraosseous access--a preliminary, observational, multicenter study.
Scand J Trauma Resusc Emerg Med
PUBLISHED: 07-22-2011
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Intraosseous (IO) access represents a reliable alternative to intravenous vascular access and is explicitly recommended in the current guidelines of the European Resuscitation Council when intravenous access is difficult or impossible. We therefore aimed to study the efficacy of the intraosseous needle driver EZ-IO in the prehospital setting.
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Biomarkers of endothelial dysfunction: can they help us deciphering systemic inflammation and sepsis?
Biomarkers
PUBLISHED: 06-29-2011
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The endothelial integrity, as mechanical barrier against microorganisms and as natural "anticoagulant", is crucial for physiologic organ function. Systemic activation of the endothelium upon inflammation, sepsis, and septic shock is always ending in blood-tissue barrier disruption. With increasing dysfunction, uncontrolled clotting activation, capillary microthrombi formation, tissue edema, local hypoxia, and ischemia are initiated. This in turn enhances a vicious circle leading to multiple organ failure and death. Therefore, biomarkers reflecting this special compartment may help in the early detection of systemic inflammation and its complications. This review provides an overview of the most important endothelial biomarkers and their possible use in sepsis.
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Linking inflammation and coagulation: novel drug targets to treat organ ischemia.
Curr Opin Anaesthesiol
PUBLISHED: 06-11-2011
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Activation of the coagulation system during ischemia/reperfusion injury is an unavoidable event and even further augmented during cardiovascular surgery. Clotting not only leads to disturbance of blood rheology but also enhances the inflammatory response. We aim to highlight the inflammatory properties of the coagulation system and novel potential therapeutic approaches targeting both features.
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Phosphorylation of vasodilator-stimulated phosphoprotein prevents platelet-neutrophil complex formation and dampens myocardial ischemia-reperfusion injury.
Circulation
PUBLISHED: 05-23-2011
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Recent work has suggested that the formation of platelet-neutrophil complexes (PNCs) aggravates the severity of inflammatory tissue injury. Given the importance of vasodilator-stimulated phosphoprotein (VASP) for platelet function, we pursued the role of VASP on the formation of PNCs and its impact on the extent of myocardial ischemia-reperfusion (IR) injury.
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Emergency airway management in trauma patients using laryngeal tube suction.
Prehosp Emerg Care
PUBLISHED: 04-26-2011
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Endotracheal intubation (ETI) is considered to be the "gold standard" of prehospital airway management of trauma patients. However, ETI requires substantial technical skills and ongoing experience. Because failed prehospital ETI is common and associated with a higher mortality, reliable airway devices are needed to be used by rescuers who are less experienced in ETI.
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Tranexamic acid partially improves platelet function in patients treated with dual antiplatelet therapy.
Eur J Anaesthesiol
PUBLISHED: 03-17-2011
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Although the impact of tranexamic acid on platelet function remains controversial, tranexamic acid is part of clinical algorithms for the management of platelet dysfunction. The goal of our prospective, observational study was to examine the effects of tranexamic acid on platelet function in patients treated with dual antiplatelet therapy compared to those who ceased antiplatelet therapy for at least 7 days.
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Peroxisome proliferator-activated receptor ?-induced T cell apoptosis reduces survival during polymicrobial sepsis.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 02-25-2011
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Despite intensive research, sepsis displays the most prevalent cause of death on intensive care units. The hallmark of sepsis is an overshooting T-cell death that reduces host defense mechanisms and that is associated with poor patient survival. Previous in vitro studies revealed that the expression of the transcription factor peroxisome proliferator-activated receptor (PPAR) ? was increased in isolated T cells of patients with sepsis.
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Soluble triggering receptor on myeloid cells-1 is expressed in the course of non-infectious inflammation after traumatic lung contusion: a prospective cohort study.
Crit Care
PUBLISHED: 02-07-2011
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The triggering receptor expressed on myeloid cells-1 (TREM-1) is known to be expressed during bacterial infections. We investigated whether TREM-1 is also expressed in non-infectious inflammation following traumatic lung contusion.
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Genetic variation of TLR4 influences immunoendocrine stress response: an observational study in cardiac surgical patients.
Crit Care
PUBLISHED: 01-31-2011
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Systemic inflammation (for example, following surgery) involves Toll-like receptor (TLR) signaling and leads to an endocrine stress response. This study aims to investigate a possible influence of TLR2 and TLR4 single nucleotide polymorphisms (SNPs) on perioperative adrenocorticotropic hormone (ACTH) and cortisol regulation in serum of cardiac surgical patients. To investigate the link to systemic inflammation in this context, we additionally measured 10 different cytokines in the serum.
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Hypothermia and anesthetic postconditioning influence the expression and activity of small intestinal proteins possibly involved in ischemia/reperfusion-mediated events following cardiopulmonary resuscitation.
Resuscitation
PUBLISHED: 01-28-2011
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Successful resuscitation after cardiac arrest is typically associated with cerebral and myocardial ischemia/reperfusion (I/R)-injury. Recently, we have demonstrated effects of therapeutic hypothermia (HT) and postconditioning with the volatile anesthetic sevoflurane (SEV) on I/R-mediated mechanisms in the heart and brain [Meybohm et al., PLoS One, 2009; Meybohm et al., Crit Care, 2010]. As the intestine is also highly susceptible to I/R-injury, we investigated the influence of HT and SEV on intestinal I/R-mediated events induced by cardiac arrest and successful resuscitation.
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Hyperoxic ventilation improves survival in pigs during endotoxaemia at the critical hemoglobin concentration.
Resuscitation
PUBLISHED: 01-11-2011
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Recently it has been demonstrated that short term hyperoxic ventilation (HV) can improve glucose metabolism, reduce pulmonary and hepatic apoptosis, and improve gastrointestinal perfusion during acute sepsis. However, it is unknown whether additional O(2) improves survival. Therefore we investigated the effects of increased plasma O(2) on survival during extreme anaemia and concomitant endotoxaemia in order to quantify the efficacy of HV.
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Novel aspects of fibrin(ogen) fragments during inflammation.
Mol. Med.
PUBLISHED: 01-03-2011
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Coagulation is fundamental for the confinement of infection and/or the inflammatory response to a limited area. Under pathological inflammatory conditions such as arthritis, multiple sclerosis or sepsis, an uncontrolled activation of the coagulation system contributes to inflammation, microvascular failure and organ dysfunction. Coagulation is initiated by the activation of thrombin, which, in turn, triggers fibrin formation by the release of fibrinopeptides. Fibrin is cleaved by plasmin, resulting in clot lysis and an accompanied generation of fibrin fragments such as D and E fragments. Various coagulation factors, including fibrinogen and/or fibrin [fibrin(ogen)] and also fibrin degradation products, modulate the inflammatory response by affecting leukocyte migration and cytokine production. Fibrin fragments are mostly proinflammatory, however, B?15-42 in particular possesses potential antiinflammatory effects. B?15-42 inhibits Rho-kinase activation by dissociating Fyn from Rho and, hence prevents stress-induced loss of endothelial barrier function and also leukocyte migration. This article summarizes the state-of-the-art in inflammatory modulation by fibrin(ogen) and fibrin fragments. However, further research is required to gain better understanding of the entire role fibrin fragments play during inflammation and, possibly, disease development.
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Hepatocyte growth factor mobilizes non-bone marrow-derived circulating mesoangioblasts.
Eur. Heart J.
PUBLISHED: 12-29-2010
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The identification of factors that mobilize subsets of endogenous progenitor cells may provide new therapeutic tools to enhance the repair of ischaemic tissue. We previously identified circulating mesenchymal cells that co-express endothelial markers (so-called circulating mesoangioblasts, cMABs) in children undergoing heart surgery with cardiopulmonary bypass (CPB). However, the mechanisms by which these cells are mobilized and their origin is unclear.
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Toll-like receptor 2 signaling triggers fatal arrhythmias upon myocardial ischemia-reperfusion.
Crit. Care Med.
PUBLISHED: 09-22-2010
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Restoration of myocardial blood flow after ischemia triggers an inflammatory response involving toll-like receptors. Toll-like receptor 2 deficiency is associated with a reduced infarct size after myocardial ischemia and reperfusion. Because a marked mortality was observed in C3HeN wild-type mice, which was absent in TLR2 mice, we tested whether cardiac arrhythmias are the underlying pathology and aimed to elucidate how toll-like receptor 2 ligation might prevent lethal arrhythmias.
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Disposable laryngeal tube suction: standard insertion technique versus two modified insertion techniques for patients with a simulated difficult airway.
Resuscitation
PUBLISHED: 09-10-2010
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The disposable laryngeal tube suction (LTS-D) is a supraglottic airway device that can be used as an alternative to tracheal tube to provide ventilation. We tested the hypothesis that, with a frontal jaw thrust insertion technique (FIT/JT), the rate of correct placement attempts in patients with a simulated difficult airway by means of a rigid cervical immobilization collar could be significantly increased compared to the standard insertion technique (SIT) recommended by the manufacturer.
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Abrogation of TLR4 and CD14 expression and signaling in human adrenocortical tumors.
J. Clin. Endocrinol. Metab.
PUBLISHED: 09-08-2010
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Adrenocortical carcinoma (ACC) is a rare tumor with poor prognosis. The expression of innate immunity receptor Toll-like receptor 4 (TLR4) was recently reported in various human tumors, and TLR4 was shown to regulate tumor immune escape processes, proliferation, and resistance to chemotherapeutical agents.
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Upregulation of TLR2 and TLR4 in the human adrenocortical cells differentially modulates adrenal steroidogenesis.
Mol. Cell. Endocrinol.
PUBLISHED: 09-01-2010
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Rapid activation of adrenal steroid release plays a pivotal role in an organisms first line of defense during sepsis. Adrenal gland function is often suppressed in critically ill patients and negatively impacts the overall survival rate. Increasingly, experimental and clinical evidence suggests that Toll-like receptors (TLRs), components of the innate immune system, play a key role in the mediation of systemic responses to invading pathogens during sepsis. In the present study, we aimed to elucidate the effect of TLR2, TLR4 and CD14 upregulation on adrenocortical cell steroidogenesis. We found that TLR4 and CD14 but not TLR2 overexpression in NCI-H295R cells inhibited basal and acute cortisol and aldosterone production. This effect could be partially explained by reduced expression of enzymes involved in the synthesis of latter steroids--CYP11B1 and CYP11B2. Together, these data suggest that TLR upregulation in the steroid producing cells may be involved in the adrenal gland dysfunction during sepsis.
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Functional role of TASK-1 in the heart: studies in TASK-1-deficient mice show prolonged cardiac repolarization and reduced heart rate variability.
Basic Res. Cardiol.
PUBLISHED: 08-31-2010
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TASK-1, a member of the recently identified K2P channel family, is mainly expressed in the heart and the nervous system. TASK-1 is regulated by several physiological and pathological conditions and functions as a background potassium channel. However, there are limited data concerning the significance of TASK-1 in cardiac physiology. We studied the functional role of TASK-1 in the heart by cardiac phenotyping the TASK-1-deficient mouse (TASK-1(-/-)). TASK-1 was predominantly expressed in the ventricles of control animals. Real-time PCR and immunoblot demonstrated that the expression of seven other K2P channels was unchanged in TASK-1(-/-) mice. No structural or functional abnormalities were found by histology and echocardiography. Electrophysiological studies recording monophasic action potentials (MAPs) showed a significant prolongation of action potential duration in spontaneously beating and atrially paced hearts, respectively. Surface ECGs of TASK-1(-/-) mice revealed a significant prolongation of the rate corrected QT interval. Telemetric ECG recordings for 24 h, during physical and pharmacological stress testing and after ischemia/reperfusion injury did not result in a higher incidence of arrhythmias. Infarct size was comparable in both genotypes. However, TASK-1(-/-) mice had a higher mean heart rate and significantly reduced heart rate variability (HRV). Time and frequency domain measurements as well as baroreceptor reflex testing revealed a sympathovagal imbalance with a shift to an increase in sympathetic influence in TASK-1(-/-) mice. In conclusion, TASK-1 plays a functional role in the repolarization of the cardiac action potential in vivo and contributes to the maintenance of HRV.
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Left ventricular dilation in toll-like receptor 2 deficient mice after myocardial ischemia/reperfusion through defective scar formation.
Basic Res. Cardiol.
PUBLISHED: 05-31-2010
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Restoration of myocardial blood flow after ischemia triggers an inflammatory response involving toll-like receptors (TLRs). TLR2(-/-)-mice show short-term advantages upon reperfusion injury as compared with WT controls. Accordingly, it has been shown that transient TLR2-blockade prior to reperfusion is associated with improved left-ventricular performance after myocardial scar formation. We present here adverse myocardial remodeling due to a chronic lack of TLR2 expression. Myocardial ischemia/reperfusion (MI/R) was surgically induced in C3HeN-mice by ligation of the left anterior descending coronary artery for 20 min, followed by 24 h or 28 days of reperfusion. TLR2(-/-)-mice and TLR2-Ab treated (T2.5) WT-mice displayed a reduction of infarct size, plasma troponin T concentrations, and leukocyte infiltration as compared with untreated controls after 24 h of reperfusion. After 28 days, however, magnetic resonance imaging revealed a marked left ventricular dilation in TLR2(-/-)-animals, which was associated with pronounced matrix remodeling characterized by reduced collagen and decorin density in the infarct scar. Our data show adverse effects on myocardial remodeling in TLR2(-/-)-mice. Although interception with TLR2 signaling is a promising concept for the prevention of reperfusion injury after myocardial ischemia, these data give cause for serious concern with respect to the time-point and duration of the potential treatment.
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Normovolemic modified ultrafiltration is associated with better preserved platelet function and less postoperative blood loss in patients undergoing complex cardiac surgery: a randomized and controlled study.
J. Thorac. Cardiovasc. Surg.
PUBLISHED: 05-19-2010
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The purpose of the investigation was to study the impact of normovolemic modified ultrafiltration (N-MUF) on hemostasis and perioperative blood loss.
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The fibrin-derived peptide Bbeta(15-42) significantly attenuates ischemia-reperfusion injury in a cardiac transplant model.
Transplantation
PUBLISHED: 04-21-2010
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The inflammatory response after prolonged ischemia and subsequent reperfusion leads to increased risk of primary organ dysfunction after cardiac transplantation. It has been demonstrated that the fibrin-derived peptide Bbeta(15-42) (also called FX06) reduces infarct size in coronary artery occlusion/reperfusion models by inhibition of leukocyte migration. Further, Bbeta(15-42) preserves endothelial barrier function. The purpose of this study was to investigate whether Bbeta(15-42) has a protective effect in cardiac allografts exposed to prolonged global ischemia and subsequent in vivo reperfusion.
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Therapeutic injection of PARP inhibitor INO-1001 preserves cardiac function in porcine myocardial ischemia and reperfusion without reducing infarct size.
Shock
PUBLISHED: 04-17-2010
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Pharmacological protection from myocardial reperfusion injury, despite plenty of approaches, has still not been realized in humans. We studied the putative infarct size (IS)-sparing capacity of poly(ADP-ribose)polymerase inhibitor, INO-1001, and focused on cardiac functional recovery during reperfusion. Male farm-bred Landrace pigs were subjected to 1-h left anterior descending coronary artery occlusion followed by 3 h of reperfusion (control). Infarct size was determined by triphenyltetrazolium chloride/Evans blue staining. Plasma markers of myocardial injury (troponin T, creatine kinase, lactate dehydrogenase) were determined upon protocol completion. Cardiac function was continuously assessed via pulmonary and femoral artery catheters. INO-1001 (1 mg/kg) was administered upon reperfusion in the treatment group. As a positive control, untreated pigs were subjected to ischemic preconditioning (10-min left anterior descending coronary artery occlusion followed by 15-min reperfusion before the intervention). Ischemic preconditioning reduced myocardial damage reflected by a smaller IS and lower plasma markers of myocardial injury. INO-1001 did not reduce IS but significantly improved functional recovery (increased stroke volume, cardiac index, and mixed venous oxygen saturation) during reperfusion compared with vehicle-treated control and ischemic preconditioning. Although we could not confirm the IS-sparing capacities of poly(ADP-ribose)polymerase inhibitor, INO-1001, the drug holds the potential of hemodynamic improvement during reperfusion.
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Influence of genetic variations in TLR4 and TIRAP/Mal on the course of sepsis and pneumonia and cytokine release: an observational study in three cohorts.
Crit Care
PUBLISHED: 04-07-2010
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It has been proposed that individual genetic variation contributes to the course of severe infections and sepsis. Recent studies of single nucleotide polymorphisms (SNPs) within the endotoxin receptor and its signaling system showed an association with the risk of disease development. This study aims to examine the response associated with genetic variations of TLR4, the receptor for bacterial LPS, and a central intracellular signal transducer (TIRAP/Mal) on cytokine release and for susceptibility and course of severe hospital acquired infections in distinct patient populations.
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Mild hypothermia alone or in combination with anesthetic post-conditioning reduces expression of inflammatory cytokines in the cerebral cortex of pigs after cardiopulmonary resuscitation.
Crit Care
PUBLISHED: 02-16-2010
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Hypothermia improves survival and neurological recovery after cardiac arrest. Pro-inflammatory cytokines have been implicated in focal cerebral ischemia/reperfusion injury. It is unknown whether cardiac arrest also triggers the release of cerebral inflammatory molecules, and whether therapeutic hypothermia alters this inflammatory response. This study sought to examine whether hypothermia or the combination of hypothermia with anesthetic post-conditioning with sevoflurane affect cerebral inflammatory response after cardiopulmonary resuscitation.
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Role of toll-like receptors and inflammation in adrenal gland insufficiency.
Neuroimmunomodulation
PUBLISHED: 02-04-2010
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Adrenal gland insufficiency - the clinical manifestation of deficient production or action of adrenal steroids - is a life-threatening disorder. Among many factors which can predispose to primary adrenal failure, an autoimmune adrenalitis and infectious agents play a major role. The initial host defense against bacterial infections is executed primarily by the pattern recognition receptors, e.g. Toll-like receptors (TLRs), expressed in cells from the innate immune system. Upon activation, TLRs have been found to regulate various levels of innate and adaptive immunity as well as control tissue inflammation. TLRs are implicated in adrenal cell turnover and steroidogenesis during inflammation. Therefore, TLRs play a crucial role in the activation of adrenal inflammation mediating adrenal gland dysfunction during septicemia.
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IL-6 may modulate the skeletal response to glucocorticoids during exacerbations of inflammatory bowel disease.
Calcif. Tissue Int.
PUBLISHED: 01-31-2010
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Whether inflammatory cytokines affect the skeletal response to glucocorticoid (GC) treatment is unclear. Our objectives were to (1) identify the cytokine(s) elevated during exacerbations of inflammatory bowel disease (IBD); (2) determine whether the cytokine(s) identified in this way is related to systemic GC sensitivity; and (3) examine whether cytokines and/or measures of GC sensitivity are related to changes in bone formation or resorption following GC therapy. We designed a combined cross-sectional and prospective study, including patients with active (n = 31) and inactive (n = 34) IBD as well as controls (n = 29). We assessed circulating concentrations of cytokines, PINP and betaCTX, as well as GC sensitivity in peripheral blood mononuclear cells. IL-6 was the only cytokine increased in active IBD, 2.35 (2.63) versus 1.64 (1.21) versus 1.31 (2.79) pg/microl active IBD, inactive IBD, and controls, respectively (median [interquartile range]) (P = 0.03, ANOVA). IL-6 was positively related to magnitude of GC sensitivity (beta = 0.02, 95% CI 0.008-0.04, P = 0.005). Following treatment with GC in active IBD, PINP decreased (P < 0.001), whereas betaCTX showed no significant change (P = 0.2). Subsequently, multiple regression analyses revealed that plasma IL-6 concentrations were inversely related to the extent of PINP suppression following GC (beta = 3.3, 95% CI 0.2-6.4, P = 0.04, adjusted for baseline PINP and duration of GC treatment), while no association was observed with GC sensitivity. In conclusion, IL-6 is elevated in active IBD and may protect against GC-induced suppression of bone formation via a mechanism which appears to be independent of systemic GC sensitivity.
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Preconditioning by toll-like receptor 2 agonist Pam3CSK4 reduces CXCL1-dependent leukocyte recruitment in murine myocardial ischemia/reperfusion injury.
Crit. Care Med.
PUBLISHED: 01-19-2010
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To test whether preconditioning with a toll-like receptor (TLR) 2 agonist protects against myocardial ischemia and reperfusion by interfering with chemokine CXCL1 release from cardiomyocytes.
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Hypothermia and postconditioning after cardiopulmonary resuscitation reduce cardiac dysfunction by modulating inflammation, apoptosis and remodeling.
PLoS ONE
PUBLISHED: 06-30-2009
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Mild therapeutic hypothermia following cardiac arrest is neuroprotective, but its effect on myocardial dysfunction that is a critical issue following resuscitation is not clear. This study sought to examine whether hypothermia and the combination of hypothermia and pharmacological postconditioning are cardioprotective in a model of cardiopulmonary resuscitation following acute myocardial ischemia.
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Accurate and continuous measurement of oxygen deficit during haemorrhage in pigs.
Resuscitation
PUBLISHED: 05-16-2009
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Haemorrhagic shock can cause organ failure and high mortality. Uncontrolled bleeding, a predetermined bleeding volume or blood pressure controlled bleeding are traditionally used to study haemorrhagic shock. These models are influenced by compensatory mechanisms preventing accurate knowledge about the severity of cellular insult. We describe the use of a method for continuous measurement of oxygen deficit during haemorrhage in pigs.
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A double blind, single centre, sub-chronic reperfusion trial evaluating FX06 following haemorrhagic shock in pigs.
Resuscitation
PUBLISHED: 05-16-2009
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Haemorrhagic shock causes ischaemia and subsequent fluid resuscitation causes reperfusion injury, jointly resulting in high morbidity and mortality. We tested whether the anti-inflammatory fibrin-derived peptide, Bbeta(15-42), also called FX06, is tissue protective in a model of haemorrhagic shock.
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Bbeta15-42 (FX06) reduces pulmonary, myocardial, liver, and small intestine damage in a pig model of hemorrhagic shock and reperfusion.
Crit. Care Med.
PUBLISHED: 05-07-2009
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The fibrin-derived peptide Bbeta15-42 (also called FX06) has been shown to reduce myocardial infarct size following ischemia/reperfusion. Hemorrhagic shock (HS) followed by volume resuscitation represents a similar scenario, whereby a whole organism is vulnerable to reperfusion injury.
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Differential expression and action of Toll-like receptors in human adrenocortical cells.
Mol. Cell. Endocrinol.
PUBLISHED: 05-05-2009
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During sepsis, an intact adrenal gland glucocorticoid stress response is critical for survival. Recently, we have shown that Toll-like receptors, particularly TLR2 and TLR4, are crucial in HPA axis regulation following inflammation, establishing a direct link between bacterial and viral ligands and the endocrine stress response. However, the exact role which TLRs play in adrenal homeostasis and malfunction is not yet sufficiently known. Using quantitative real-time PCR, confocal microscopy and the NF-kappaB reporter gene assay, we aimed to analyse both, expression and function of all relevant TLRs in the human adrenocortical cell line-NCI-H295R and adrenal cells in primary culture. Our results demonstrate a differential expression pattern of TLR1-9 in human adrenocortical cells as compared to immune cells and adrenocortical cancer cells. Consequently, activation of these cells by bacterial ligands leads to differential induction of cytokines including IL6, IL8 and TNF-alpha. Therefore, Toll-like receptors expression and function is a novel feature of the adrenal stress system contributing to adrenal tissue homeostasis, regeneration and tumorigenesis.
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Innate immunity, coagulation and surgery.
Front Biosci (Landmark Ed)
PUBLISHED: 03-11-2009
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Inflammation is the hosts defense mechanism to infection or trauma including surgical procedures. In the clinic, non-infectious inflammation plays an important part in cardiology (e.g. Percutaneous transluminal coronary angioplasty, PTCA), intensive care medicine (e.g. polytrauma), cardiac (e.g. extracorporeal circulation) and vascular surgery (e.g. reperfusion injury). An imbalance of the inflammatory response can cause an acute condition like sepsis or long-term Cardiovascular disease (CVD), both of which are leading killers in the Western world. Alterations in coagulation, innate immunity and endothelial function represent key aspects in the mechanism of inflammation and are the link between the pathogenesis of these two diseases. Studying inflammatory pathways or targeting specific mediators during inflammation may help to develop strategies to improve the clinical outcome of patients undergoing major surgery, where postoperative inflammation plays a crucial role.
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Peptide Bbeta(15-42) preserves endothelial barrier function in shock.
PLoS ONE
PUBLISHED: 01-12-2009
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Loss of vascular barrier function causes leak of fluid and proteins into tissues, extensive leak leads to shock and death. Barriers are largely formed by endothelial cell-cell contacts built up by VE-cadherin and are under the control of RhoGTPases. Here we show that a natural plasmin digest product of fibrin, peptide Bbeta15-42 (also called FX06), significantly reduces vascular leak and mortality in animal models for Dengue shock syndrome. The ability of Bbeta15-42 to preserve endothelial barriers is confirmed in rats i.v.-injected with LPS. In endothelial cells, Bbeta15-42 prevents thrombin-induced stress fiber formation, myosin light chain phosphorylation and RhoA activation. The molecular key for the protective effect of Bbeta15-42 is the src kinase Fyn, which associates with VE-cadherin-containing junctions. Following exposure to Bbeta15-42 Fyn dissociates from VE-cadherin and associates with p190RhoGAP, a known antagonists of RhoA activation. The role of Fyn in transducing effects of Bbeta15-42 is confirmed in Fyn(-/-) mice, where the peptide is unable to reduce LPS-induced lung edema, whereas in wild type littermates the peptide significantly reduces leak. Our results demonstrate a novel function for Bbeta15-42. Formerly mainly considered as a degradation product occurring after fibrin inactivation, it has now to be considered as a signaling molecule. It stabilizes endothelial barriers and thus could be an attractive adjuvant in the treatment of shock.
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Cecum ligation and dissection: a novel modified mouse sepsis model.
J. Surg. Res.
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The fact that many sepsis therapeutics failed to be translated into the human indicates that there is still a serious need to reassess our models of sepsis research. We aimed to develop a novel modified model of sepsis in the mouse, which simulates the clinical situation more accurately.
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Remote ischemic preconditioning regulates HIF-1? levels, apoptosis and inflammation in heart tissue of cardiosurgical patients: a pilot experimental study.
Basic Res. Cardiol.
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Transient episodes of ischemia in a remote organ (remote ischemic preconditioning, RIPC) bears the potential to attenuate myocardial injury, but the underlying mechanisms are only poorly understood. In the pilot experimental study presented we investigated cellular and molecular effects of RIPC in heart tissue of cardiosurgical patients with cardiopulmonary bypass (CPB) and focussed on apoptotic events, local and systemic inflammation as well as the regulation of the hypoxia induced factor-1? (HIF-1?). RIPC was induced by four 5-min cycles of transient upper limb ischemia/reperfusion using a blood-pressure cuff. Right atrial tissue and serum were obtained from patients receiving RIPC (N = 32) and control patients (N = 29) before and after CPB. RIPC patients showed reduced troponin T serum concentrations in the first 48 h after surgery (P < 0.05 vs. control) indicating cardioprotective effects of RIPC. Samples from RIPC patients that were collected before CPB contained significantly increased amounts of HIF-1? and procaspase-3 (HIF-1?: P < 0.05 vs. control, procaspase-3: P < 0.05 vs. control), whereas activities of caspases 3 and 7 were by trend reduced. Samples from RIPC patients that were taken after CPB showed an increased activity of myeloperoxidase (P < 0.05 vs. control; P < 0.05 vs. RIPC before CPB) as well as elevated tissue concentrations of the interleukin (IL)-1? (P < 0.05 vs. RIPC before CPB). Serum levels of IL-8, IL-1? and TNF? were significantly increased in RIPC patients before CPB (P < 0.05 vs. control before CPB). In summary, RIPC regulates HIF-1? levels, apoptosis and inflammation in the myocardium of cardiosurgical patients and leads to increased concentrations of circulating cytokines.
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Priming with synthetic oligonucleotides attenuates pressure overload-induced inflammation and cardiac hypertrophy in mice.
Cardiovasc. Res.
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Inflammation and Toll-like receptor (TLR) signalling have been linked to the development of cardiac hypertrophy following transverse aortic constriction (TAC). In the present study, we investigated whether pre-treatment with the synthetic TLR9 ligands 1668-thioate or 1612-thioate modulates the progression of TAC-induced cardiac inflammation and hypertrophy.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.