 Γεια σας! Είμαι Αθήνα Ραμμου και είμαι πρόσφυσιογησης της Γέντερας Βαθμιστικής Βαθμιστικής. Εγγραφήσαμε από ΤΕΤΑΑ στην 2014. Θα ευχαριστώ για την οικογένωση για να κάνω αυτή η δημότητα. Στην αυτή η δημότητα που είναι δημιουργητική για οι διεθνικές της κοινωνικής κοινωνίας. Όπως όλοι οι Ελληνικές που θέλουμε να κάνουμε, θα θέλω να σας πω πρώτα ένα ιστορία για την πρώτη κοινωνικής κοινωνικής κοινωνικής κοινωνίας. Η δημότητα της κοινωνίας είναι Αγνωδάης. Προσπαθούσε στην Αισιανία Ταθένση στην 4η αιθνή Βαθμιστικής, όπου στην τέτοια κοινωνία οι κοινωνίες ήταν ανοιχές από την κοινωνική κοινωνικής κοινωνικής κοινωνικής. Φυγήσαμε, εξέγγεστε όλες,shapedagogue!? Γνωρίζουμε, favorragio dopamine calls μιαouv. Αγνωτήθηκαν να προσφαθεί τα κομμάτια της λαμβάνης που είχαν φορά ή θέλουν να εξοπηθούν αδερφούς. Συμβουλήθηκαν να αγνωτήθηκαν να εξοπηθούν την αυτης και ήταν ανοιγμένη να συμβουλήσουν τη δεύτερη. Οι άλλοι οι δεύτερες που αγνωτήθηκαν την αγνωτήθηση της αυγήκας έκουσαν να υποφαθούν την αυγήκη της αυγήκας. Στην αγραδία, πριν από το αριό Βαγγούς, Αγγροδάης, πάνω από αυτού, αφήτησε τα κλώματα, αφήτησε ότι ήταν η γιάννη. Είναι αυτοκλή με το αγραδείο της λόγας, που αφήτησε τα κομμάτια από τη δημιουργία της λόγας, αλλά ήταν δημιουργημένη από οι γυναίκες της σημείας που έλεγε. Στην σχέση της, η λόγη ήταν αφήτηση να αφήτησε τη δημιουργία της λόγας, και να προηγήσουν themselves for their equal value. Today I'm going to present you about... to talk about systemic inflammatory response syndrome in cardiopulmonary bypass and the role of NETs. First of all, we will talk about some historical facts, of course. We will talk about the following facts. First of all, we will talk about some historical facts. Of course, mechanism of inflammation during cardiopulmonary bypass, definition of sears, NETs, what are they, the role of NETs in sears, methods for the treatment of sears. The need for a bloodless, still surgical field led to the discovery of the heart lung machine. A milestone was the discovery of heparin that allowed the extracorporeal circulation to take place without the danger of blood clotting in the circuit. 1952, the first successful intracardia correction of a congenital heart defect by Ues and Lilehi at the University of Minnesota. 1954, first successful open heart surgery using cross-circulation. 1955, a use of the first heart lung machine with Gibbon type oxygenator. The evolution of cardiac surgery, the discovery of cardiopulmonary bypass machine along with the mechanical circulatory devices since 1950 have made cardiac procedures safe, improved the quality and longevity of life of patients. Extracorporeal circulation makes multiple changes in normal circulation of blood and organ function causing production of inflammatory mediators. With the improvement in surgical techniques and technology evolution, many of the undesirable reactions of the body to extracorporeal circulation have been decreased. Nevertheless, the systemic inflammatory response syndrome in extracorporeal circulation remains one of the main causes of organ dysfunction in patients undergoing cardiac surgery. As we like to say, the science of perfusion is manipulation of the blood. Blood is the important link between the patient and the heart lung machine. Many systems of the body are affected by the circulation of the blood in the heart lung machine and there is activation of platelets, neutrophils, complement system, fibrinolytic system and innate and acquired immunity. According to American College of Chest Physicians and the Society of Critical Care Medicine in 1992, systemic inflammatory response syndrome is a common systemic response to a wide variety of insults. Two or more of the following clinical manifestations must be fulfilled for the diagnosis. Body temperature higher than 38°C or lower than 36°C. Heart rate more than 90 bits per minute. Respiratory rate more than 20 per minute or PCO2 less than 32 mmHg. Lucocide count more than 12,000 or the presence of more than 10% i immature neutrophils. Systemic inflammatory response syndrome is mainly initiated from blood contact to surface other than endothelium, such as the cardiopulmonary bypass circuit. From blood contact to foreign surface, a series of reactions are initiated that includes absorption of proteins, initiation of coagulation system, of complement system, activation of platelets, leukocytes and neutrophils. First of all, the exposure of blood to the extracorporeal circuit activates the contact system. Then the complement system is also activated mainly through its alternative pathway. The cardiopulmonary bypass circuit lacks than the thylial cell, surface inhibitors, that normally limit cofactor C3 activation and this contact activation, along with the stimulus of calligrain, provokes the formation of anaphyloatoxins C3a and C5a with anaphylactic and chemotactic activity. Cytochines. Compliment factors and their degradation products can exert an immunomodulatory effect inducing the synthesis of pro-inflammatory cytokines. Cytochines are intercellular messengers produced by tissues in response to different stimuli. They have been generally considered to be products for mature leukocytes within the lymphatic system, but recent reports show that their secretion may also be modulated by different cell lines such as platelets and endothelial cells. The role of cytokines and the pathophysiology of the cardiopulmonary bypass-related acute-phase reaction has been studied extensively. Besides the well-documented increased levels of pro-inflammatory cytokines, the role of anti-inflammatory cytokines and the balance among these cytokines may be important in determining the level of the inflammatory response. The toxinia is another activator for the cardiopulmonary bypass-related inflammatory reaction. Bacteria lipopolysaccharide is released by gram-negative bacteria during their growth and replication after the disruption of bacterial cell membranes consequent to antibiotic administration or low-flow blood flow. In plasma endotoxin binds to LPS binding protein, a human serum protein, whose concentration rises during the acute-phase reaction, forming an endotoxin LPS binding protein complex. At the presence of endotoxin in patients' blood after cardiopulmonary bypass has been demonstrated in a number of studies. Cardiopulmonary bypass is also associated with a number of studies Cardiopulmonary bypass is also associated with a deficit in platelet function and number. Fibrinogen is an important cofactor in platelet adhesion and is essential for platelet to platelet binding. Factors associated with cardiopulmonary bypass are hypothermia and shear forces, exposure to artificial surfaces, the use of exogenous drugs, the release of endogenous chemicals, hemo dilution from pump prime that contributes to further thrombocytopenia. Cardiopulmonary bypass and aorta cross-clamping induce myocardial hypoxia and ischemia, both of which are pro-inflammatory stimuli. Together with other factors such as complement, histamine, pro-inflammatory cytokines and the toxin and thrombin, ησκήνια contributes to the activation of endothelial cells and leukocytes, the effectors of inflammatory cytotoxicity. Last but not least, we have the activation of neutrophils. Neutrophils are a central cell type in the mediation of the systemic inflammatory response. They comprise 60% of the white blood cell count and their activation and cytotoxicity. Their activation and cytotoxic capability are an essential aspect of the body's ability to fight infection. There are four ways of neutrophil defense in bacteria. First of all, neutrophil recruitment. Neutrophil senses bacteria, slows and squeezes through blood vessels, moves towards bacteria which have been marked by antibodies for ingestion. Second, pagocytosis. Neutrophil engulfs and destroys marked bacteria. Another way is by releasing bactericidal activity, bactericidal substances that kill bacteria. And then fourth, the fourth way is releasing DNA structures that trap bacteria, nets. Neutrophil extracellular traps. Brinkman and colleagues in 2004 showed that neutrophil stimulation with PMA released web-like structures of DNA coated with histones, elastase, myeloperoxidase and cathaspin G. These structures were given the name neutrophil extracellular traps which were initially proposed to immobilize and trap and kill bacteria extracellularly. Nets from the one hand contribute to defense against infection. But from the other hand, implicated in the pathophysiology of multiple diseases, such as vasculitis, trolley, thrombotic microangiopathy, preeclampsia, cancer metastasis, acute respiratory distress syndrome, and acute local liberation of histones, such as histone-free and myeloperoxidase, are thought to cause endothelial injury and exacerbate inflammation induced organ injury. Recent evidence also implicates a potential role of nets in linking inflammation with thrombosis. The formation and deposition of nets could impair perfusion at the microcirculation level because it has been demonstrated in some models of organ dysfunction in which microcirculatory compromise is well described, such as the myocardial no-reflow phenomenon and septic acne. In the context of cardiac surgery, production of nets could have pathophysiological implications. Patients with vascular disease or comorbidities, such as diabetes, may have chronic inflammation resulting in a priming of circulating neutrophils before surgery. The general inflammatory reaction, triggered by cardiopulmonary bypass, may consequently result in a burst of nets production in the perioperative period. Occlusion and injury of the pulmonary and systemic microcirculation in trans-nets formation, triggered by cardiopulmonary bypass, may be implicated in the pathogenesis of adverse patients' outcomes by inducing organ injury in multiple systems. A study that was published in 2020 by Bob Yan Shulini and his colleagues demonstrated that circulating nets increased during cardiopulmonary cardiac surgery. The exposure of blood to the extracorporeal circuit during cardiopulmonary bypass may trigger production of nets. Now, let's see the strategies to control cardiopulmonary bypass that have been developed and are based in three pillars. Improvement of biocompatibility of artificial surface, temporary inhibition of blood cells activation during cardiopulmonary bypass among the bio-activities and effects of inflammatory mediators. Biocompatibility of an artificial surface depends on the composition, chemical and physical attribute of protein mosaic on the surface, one in contact with blood. The ideal biosurface should bind albumin and prevent absorption of fibrinogen, factor 12 and high molecular weight calicrine, suppress the activation of C3 and decrease the molluses during cardiopulmonary bypass. Coating also with various agents on the INAT layer of circuit to suppress inflammation should be beneficial. When we say blood anesthesia we are talking about temporal prevention of activation of blood cells from the stimuli of the biosurfaces by the applications of pharmaceutical agents during blood exposure to the materials. Platelet inhibitors prostaglandin inhibitor 2 inhibits thrombin activation but causes vasodivalation severely. Better choice is nitric oxide gas because of its inhibiting effects on adhesion and aggregation of platelets, neutrophils and activation of complement that most importantly it's short half-time, half lifetime which not only causes no systemic hypotension but also makes it easier to determine, to terminate the inhibiting effects on platelets after cardiopulmonary bypass. Glucocorticoids have long been used to reduce inflammation. They act to reduce early inflammatory processes such as increased capillary permeability edema formation leukocyte migration and also later manifestations such as the proliferation of capillaries and deposition of collagen. The primary indication for the use of the serine protease inhibitor A-proteinin in cardiac surgery is related to its role as an inhibitor of the contact pathway of intrinsic coagulation. A large number of studies have shown the ability of A-proteinin to reduce blood loss during and after cardiac surgery. In Europe, A-proteinin is approved to be used in low risk patients for cabbages only. Superoxide dismutase combined with catalase protects host tissues from oxidative damage from activated neutrophils. Other substances as manitol, alloporinol, vitamin C could be useful to reduce very radical generation. Monoclonial antibodies against cytokines and thrombox RNA2 have shown some protective effect on lungs. The perfusionists, we know all the mechanical approaches that we can do to reduce the inflammation responses. One of them is the use of emo-concentration filters that have been demonstrated to remove pro-inflammatory cytokines and to improve outcomes. Also, the heparincoated circuits there are some studies that show that they also have good outcomes and in Europe there is a great tendency to use microcircuits, the MEAC that reduce the surface area in which the blood come in contact. Pulsatile perfusion it shows to have better gut perfusion and then as an extension less endotoxins that circulate in the blood. Temperature, conflicting results and studies, they have better outcomes with normothermia but if vasopressors are needed then increased inflammatory response have been shown. Cardiotomous action blood and midiastinal chat blood are important resources of inflammatory mediators due to the direct blood air contact and the damage of blood cells caused by negative pressure some researchers insist on discarding this blood from the patient. In conclusion, Sears has been remained one of the major causes of cardiopulmonary associated organ dysfunction. The mechanism of Sears during cardiopulmonary bypass includes interaction of blood and artificial surface and endotoxinia. Neutrophils contribute to organ injury through the liberation of DNA stones like structures named neutrophil extracellular traps. Strategies to control cardiopulmonary bypass related Sears include improvement of biocompatibility blood anesthesia inhibition of inflammatory mediators I would like to mark again the exclamatory study by Govgen and Zouligny that it was demonstrated for the first time that circulating nets increase during cardiac surgery the exposure of blood to the extracorporeal circuit during cardiopulmonary bypass may trigger production of nets whether the phenomenon may predispose patients to complications after cardiac surgery should be further investigated to determine if circulating nets represent a potential treatment target. Due to the pandemic with COVID-19 I would like to share with you some information about nets and COVID-19 that I found really interesting. Coronary virus disease as we know is a novel viral infused respiratory disease that in 10 to 15% of patients progresses to acute respiratory distress syndrome triggered by a cytokine storm. In this study autopsy results and literature are presented supporting the hypothesis that a little known yet powerful function of neutrophils, the ability to form neutrophil extracellular traps may contribute to organ damage and mortality in COVID-19 patients. If this hypothesis is correct targeting nets directly or indirectly with existing drugs may reduce the clinical severity of COVID-19. Excess nets may elicit the severe multi-organ consequences of COVID-19 via their known effects on tissues and the eye immune vascular and coagulation systems. Targeting nets should be there for be considered by the biomedical community. Future is near and is expected very promising. Thank you.