Post‐cardiac arrest level of free‐plasma <scp>DNA</scp> and <scp>DNA</scp>‐histone complexes

Jeppesen, A. N.; Hvas, Anne‐Mette; Grejs, Anders Morten; Duez, Christophe Henri Valdemar; Sørensen, Boe Sandahl; Kirkegaard, Hans

doi:10.1111/aas.12882

Cited by 7 publications

(12 citation statements)

References 23 publications

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“…Consistent with our hypothesis and in agreement with the existing literature, dogs with GDV syndrome had significantly greater median plasma cfDNA, HMGB1, and PCT concentrations compared to healthy controls. Human and canine data suggests that cfDNA in the plasma derives from neutrophil extracellular trap formation and cell death ( 9 , 10 , 14 ). As such, the greater concentrations of cfDNA documented in GDV dogs could originate from gastric ischemia and necrosis, or from tissue damage resulting from global hypoperfusion and systemic inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…Obtaining these samples would be more logistically difficult, but might be more discriminant than observation at presentation. As a parallel, although cfDNA concentrations are prognostic in humans with bacteremia ( 36 , 37 ), they are not prognostic in cardiac arrest, a syndrome characterized by ischemia and reperfusion injury ( 9 ). Additionally, mechanisms other than necrosis have been postulated to explain the increase in plasma concentrations of cfDNA in people, including neutrophil extracellular trap formation and the active release of cfDNA as a method of intercellular communication ( 8 , 10 ).…”

Section: Discussionmentioning

confidence: 99%

“…Plasma cell-free DNA (cfDNA) has been receiving growing attention as a biomarker in critically ill humans. The precise origin of this circulating cfDNA remains unclear, but cells undergoing necrosis or apoptosis in addition to leukocytes forming extracellular traps are the most likely sources ( 8 , 9 ). In healthy people and in healthy dogs, plasma cfDNA concentrations are low, while increased concentrations have been detected in many conditions characterized by systemic inflammation and extensive tissue injury ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

“…In healthy people and in healthy dogs, plasma cfDNA concentrations are low, while increased concentrations have been detected in many conditions characterized by systemic inflammation and extensive tissue injury ( 10 ). Independent of the underlying disease, cfDNA concentrations reflect the severity of cell damage and are prognostic in cardiac arrest, ischemia/reperfusion injury, shock, trauma, and sepsis ( 9 – 12 ). The veterinary literature in this area is limited, but increased blood cfDNA concentrations have been documented in dogs with immune-mediated hemolytic anemia, cancer, sepsis, and trauma ( 13 – 15 ).…”

Section: Introductionmentioning

confidence: 99%

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Cell-Free DNA, High-Mobility Group Box-1, and Procalcitonin Concentrations in Dogs With Gastric Dilatation–Volvulus Syndrome

et al. 2018

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Canine gastric dilatation–volvulus (GDV) is a life-threatening disease characterized by extensive tissue ischemia, tissue hypoperfusion, and systemic inflammation. Biomarkers that better reflect the severity of gastric necrosis and systemic inflammation would aid clinicians in the management of these patients. This study aimed to investigate the prognostic significance of cell-free DNA (cfDNA), high-mobility group box-1 (HMGB1), and procalcitonin (PCT) in dogs with GDV. Concentrations of cfDNA, HMGB1, and PCT were measured in citrated plasma samples collected from 29 dogs with GDV at hospital admission. Additional data collected included baseline lactate concentrations, APPLEfast score, evidence of gastric necrosis, occurrence of postoperative complications, and outcome. Twenty-four healthy dogs were sampled as controls. Continuous variables between groups were compared with the Mann–Whitney U and correlations between continuous variables were assessed by calculation of Spearman’s correlation coefficient. Alpha was set at 0.05. Dogs with GDV had significantly greater concentrations of cfDNA, HMGB1, and PCT compared to controls (P = 0.0009, P = 0.004, and P = 0.009, respectively). PCT concentrations were significantly higher in non-survivors compared to survivors (P = 0.008). Dogs with gastric necrosis had significantly greater lactate concentrations compared to dogs without gastric necrosis (P = 0.0005). The APPLEfast score was not prognostic. Lactate and PCT concentrations were moderately, positively correlated (rs 0.51, P = 0.0005). Concentrations of the inflammatory biomarkers cfDNA, HMGB1, and PCT are increased in canine GDV. Only lactate and PCT concentrations were prognostic in this population of GDV dogs and were predictive of the presence of gastric necrosis and of non-survival to hospital discharge, respectively.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cell-Free DNA, High-Mobility Group Box-1, and Procalcitonin Concentrations in Dogs With Gastric Dilatation–Volvulus Syndrome

et al. 2018

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“…Recent observations have highlighted the important role of DAMPs, which can be actively released by ischemic or impaired cells and be involved in the development of DIC ( 25 , 26 ). PCAS patients were found to have high levels of DAMPs, including cell-free DNA (cfDNA) ( 27 – 30 ), DNA-binding proteins such as histones (DNA–histones complexes) ( 30 ), and high-mobility group box 1 protein (HMGB1) ( 31 ). cfDNA binds factor XII (FXII) and high-molecular-weight kininogen and triggers FXII- and factor XI-dependent blood coagulation ( 32 – 34 ).…”

Section: Pathophysiologymentioning

confidence: 99%

Coagulofibrinolytic Changes in Patients with Post-cardiac Arrest Syndrome

Wada

2017

Front. Med.

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Whole-body ischemia and reperfusion due to cardiac arrest and subsequent return of spontaneous circulation constitute post-cardiac arrest syndrome (PCAS), which consists of four syndromes including systemic ischemia/reperfusion responses and post-cardiac arrest brain injury. The major pathophysiologies underlying systemic ischemia/reperfusion responses are systemic inflammatory response syndrome and increased coagulation, leading to disseminated intravascular coagulation (DIC), which clinically manifests as obstruction of microcirculation and multiple organ dysfunction. In particular, thrombotic occlusion in the brain due to DIC, referred to as the “no-reflow phenomenon,” may be deeply involved in post-cardiac arrest brain injury, which is the leading cause of mortality in patients with PCAS. Coagulofibrinolytic changes in patients with PCAS are characterized by tissue factor-dependent coagulation, which is accelerated by impaired anticoagulant mechanisms, including antithrombin, protein C, thrombomodulin, and tissue factor pathway inhibitor. Damage-associated molecular patterns (DAMPs) accelerate not only tissue factor-dependent coagulation but also the factor XII- and factor XI-dependent activation of coagulation. Inflammatory cytokines are also involved in these changes via the expression of tissue factor on endothelial cells and monocytes, the inhibition of anticoagulant systems, and the release of neutrophil elastase from neutrophils activated by inflammatory cytokines. Hyperfibrinolysis in the early phase of PCAS is followed by inadequate endogenous fibrinolysis and fibrinolytic shutdown by plasminogen activator inhibitor-1. Moreover, cell-free DNA, which is also a DAMP, plays a pivotal role in the inhibition of fibrinolysis. DIC diagnosis criteria or fibrinolysis markers, including d-dimer and fibrin/fibrinogen degradation products, which are commonly tested in patients and easily accessible, can be used to predict the mortality or neurological outcome of PCAS patients with high accuracy. A number of studies have explored therapy for this unique pathophysiology since the first report on “no-reflow phenomenon” was published roughly 50 years ago. However, the optimum therapeutic strategy focusing on the coagulofibrinolytic changes in cardiac arrest or PCAS patients has not yet been established. The elucidation of more precise pathomechanisms of coagulofibrinolytic changes in PCAS may aid in the development of novel therapeutic targets, leading to an improvement in the outcomes of PCAS patients.

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Monocyte subset distribution and surface expression of HLA-DR and CD14 in patients after cardiopulmonary resuscitation

Asmussen

Busch

Helbing

et al. 2021

Sci Rep

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Systemic inflammation is a major feature of the post-cardiac arrest syndrome. The three monocyte subpopulations are thought to play an important role in this inflammatory state because they are endowed with numerous pattern recognition receptors, such as CD14, that have been associated with ischemia–reperfusion injury. By contrast, an exaggerated antiinflammatory response has also been described following cardiac arrest, which may be mediated by downregulation of antigen presentation receptor HLA-DR. We report the composition of monocyte subpopulations and the expression of CD14 and HLA-DR following cardiac arrest. Blood specimens were collected from 32 patients at three timepoints in the first 48 h after cardiac arrest. Monocyte subset composition was determined by flow cytometry based on the expression of CD14, CD16, and HLA-DR. Monocyte subset composition and the expression of CD14 and HLA-DR were correlated with patient outcomes. The results were compared to 19 patients with coronary artery disease. Cardiac arrest patients showed a significant decline in the percentage of nonclassical monocytes. Monocyte CD14 expression was upregulated after 24 h and correlated with the time to return of spontaneous circulation. Downregulation of HLA-DR expression was observed mainly among classical monocytes and significantly correlated with the dose of norepinephrine used to treat shock. Downregulation of HLA-DR among nonclassical and intermediate monocytes was significantly associated with disease severity. Our data demonstrate the disturbance of monocyte subset composition with a significant decline in nonclassical monocytes at an early stage following cardiac arrest. Our findings suggest the simultaneous presence of hyperinflammation, as evidenced by upregulation of CD14, and monocyte deactivation, characterized by downregulation of HLA-DR. The extent of monocyte deactivation was significantly correlated with disease severity.

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Post‐cardiac arrest level of free‐plasma DNA and DNA‐histone complexes

Abstract: An increased level of DNA-histone complexes was associated with increased mortality and that the level of total free-plasma DNA was elevated post-cardiac arrest.

Cited by 7 publications

References 23 publications

Cell-Free DNA, High-Mobility Group Box-1, and Procalcitonin Concentrations in Dogs With Gastric Dilatation–Volvulus Syndrome

Cell-Free DNA, High-Mobility Group Box-1, and Procalcitonin Concentrations in Dogs With Gastric Dilatation–Volvulus Syndrome

Coagulofibrinolytic Changes in Patients with Post-cardiac Arrest Syndrome

Monocyte subset distribution and surface expression of HLA-DR and CD14 in patients after cardiopulmonary resuscitation

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