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Effect of mannitol injection by intravenous catheter on ear vein endothelial cell apoptosis and venous thrombus in rabbits

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Abstract

To evaluate the effect of mannitol injection into the rabbit ear vein by intravenous catheter on endothelial cells apoptosis, thrombus formation, the expression of plasma tissue factor (TF) and von Willebrand factor (vWF). Sixty-four Zealand rabbits were randomly divided into experiment and control group and received 20% mannitol or normal saline via ear margin veins, respectively. Both groups were injected daily. On days 1, 3, 5, and 7 after catheterization, rabbits were subjected to intraperitoneal anesthesia and their ear veins were isolated and then subjected to hematoxylin and eosin staining. Cell apoptosis was evaluated using TUNEL (terminal deoxynucleotide transferase mediated d-UTP nick end labeling) staining, and the levels of TF and vWF were analyzed by enzyme-linked immunosorbent assay. Compared with the control group, the experiment group showed significantly increased thrombus formation (p < 0.05), and a significant higher rate of apoptosis in endothelial cells (p < 0.05) on days 3, 5, and 7. In addition, the experiment group showed significant elevation of plasma TF and vWF on days 3, 5, and 7 (p < 0.05). Continuous mannitol injection by intravenous catheterization induces more serious venous thrombus formation and endothelial cells apoptosis and higher TF and vWF levels than normal saline injection. These data suggest that clinical use of hyperosmotic mannitol by intravenous catheter may exert direct deleterious effects on vascular endothelium.

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... When the collagen fibers were exposed, the process of coagulation was initiated, thus increasing the chance of thrombosis. At the same time, the deposits adhering to the inner wall of the blood vessel are not easily removed and is easy to damage the vascular endothelial cells at the adhesion site, thereby inducing the formation of intravascular thromboses 14 . When using pulsed flush, the sealing fluid flows to the tip of the SPC in a disordered turbulent flow, which can effectively remove the deposits adhering to the inner wall of the blood vessel, thereby reducing the stimulation and damage of the deposits on the inner wall of the blood vessel at the distal end of the puncture point, and reducing thrombosis [13][14] . ...
... At the same time, the deposits adhering to the inner wall of the blood vessel are not easily removed and is easy to damage the vascular endothelial cells at the adhesion site, thereby inducing the formation of intravascular thromboses 14 . When using pulsed flush, the sealing fluid flows to the tip of the SPC in a disordered turbulent flow, which can effectively remove the deposits adhering to the inner wall of the blood vessel, thereby reducing the stimulation and damage of the deposits on the inner wall of the blood vessel at the distal end of the puncture point, and reducing thrombosis [13][14] . As shown in the results of this study, the uniform flush was more likely to form thrombus than the pulsed flush (p < 0.05). ...
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... Beyond that, the increase of Mannitol could damage the endothelial cells and activate the coagulation pathway by promoting TF and vWF expression, leading to intravascular thrombosis (Fletcher et al., 2014;Mo et al., 2015). Myo-Inositol, a Ca 2+ sensor mesenchymal interaction molecule, induces thrombosis by promoting the endocytosis and deposition of Ca 2+ (Volz et al., 2020). ...
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... Böylece vasküler endotelyal hasar ve apoptoz indüklenir. Aynı zamanda, prostaglandinlerin salınması ile inflamasyon tetkiklenir, vazokonstrüksiyon oluşur (20,21,22). Deneysel modellerde genellikle tavşan kulak veninden 2,5 ml/kg/gün veya 10 ml/gün dozundan 5-15 dk süresince %20 mannitol infüzyonu uygulanmış ve 2-7 gün içinde kimyasal tromboflebit oluştuğu gözlenmiştir (23). ...
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YÜZEYEL VENÖZ HASTALIKLAR HAYVAN MODELLERI
... In addition, previous findings indicated that the pathogenesis of chronic inflammation may be associated with the promotion of thrombus formation and dysfunction of platelet function, as determined by in vivo imaging (11). Furthermore, research has identified that apoptosis of vascular endothelial cells (VECs) is an important indicator for the severity of a venous thrombus (12). ...
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The endothelium is pivotal in the control of haemostasis and thrombosis because it is the primary source of many of the major haemostatic regulatory molecules. Healthy endothelial cells, unlike extravascular cells, are anticoagulant and antithrombotic. This is due to the regulated secretion of antiplatelet agents, including prostacyclin and nitric oxide. Following vessel injury, platelet adhesion to exposed matrix requires von Willebrand Factor, another endothelial cell product. Local generation of thrombin causes a series of receptor-mediated endothelial cell functional responses, while the surface of the endothelium is additionally the site for inactivation of thrombin by antithrombin, and its conversion to a coagulation inhibitor by interaction with thrombomodulin. Endothelial cells are also the source of circulating tissue-type plasminogen activator and its inhibitor, and Tissue Factor pathway inhibitor. In disease states, many of these endothelial cell properties are perturbed towards a more procoagulant and prothrombotic phenotype.
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The purpose of this study was to evaluate whether lengthening the dwell time of peripheral i.v. catheters from 72 hours to 144 hours resulted in increased rates of phlebitis and/or infiltration. The study was conducted in medical/surgical units at a 110-bed teaching hospital with an i.v. team. Kaplan-Meier estimates of the success and failure and conditional failure probabilities were calculated for phlebitis and infiltration scores. Log rank tests were used to test for an association between the covariates and the time until failure. Drug irritation was the most significant predictor of phlebitis and infiltration rates in this study. The total difference in the estimated failure rates for the catheter lasting 6 days versus a new catheter inserted for another 3 days is 1.3%. Because the conditional failure probability estimates for days 4, 5, and 6 are slightly higher than for days 1, 2, and 3, consideration may be given to extending the dwell time of a peripheral i.v. catheter beyond 72 hours under certain circumstances.
Article
This study compares selected laboratory values of blood samples obtained by means of venipuncture and by means of a peripheral intravenous catheter after a normal saline solution bolus. In this prospective experimental study, each participant served as his or her own control. Hospital employees volunteered in the emergency department of a tertiary-care teaching hospital. Participants had a peripheral catheter placed in one upper extremity and received a 200-mL bolus of normal saline solution during a 10-minute period. After a 2-minute wait period, a 12-mL aspirate was withdrawn directly from the saline solution lock. A second 12-mL aspirate was also obtained. Concurrently, venipuncture was performed on the other upper extremity. All 3 samples were analyzed for CBC, electrolytes, blood urea nitrogen, creatinine, glucose, liver function tests, and prothrombin time/international normalized ratio (PT/INR). Limits of agreement analysis based on the definition of clinical equivalence, as determined by surveying residency-trained and board-certified emergency physicians, was used to compare the results of catheter aspirates with those of venipuncture aspirates. Thirty-three volunteers participated. When comparing venipuncture versus first aspirate, 16 of the 19 laboratory tests evaluated had 99% agreement intervals that were within the predetermined definition of clinical equivalence. Potassium, bicarbonate, and glucose did not demonstrate clinical equivalence, and this difference persisted after a 12-mL discard volume. This study supports the use of blood samples obtained by means of aspiration from a peripheral catheter when testing for CBC, blood urea nitrogen, creatinine, liver function tests, and PT/INR in healthy-appearing patients. Catheter aspiration, when testing for electrolytes and glucose, may be reasonable in a more select group of patients.
Article
Peripheral vein catheter patency and infusion thrombophlebitis remains a significant problem in everyday clinical practice. The aim of the study was to investigate the epidemiology of peripheral vein complications and to evaluate three different methods for the maintenance of peripheral vein catheter patency and the prevention of vein thrombophlebitis. A total of 300 post-operative patients undergoing elective orthopaedic surgery were prospectively studied. Patients were divided into three groups: controls--catheters not flushed following drug administration; saline group--the catheters flushed with 3 mL of normal saline 0.9% after each catheter use; heparin group--the catheters flushed with 3 mL of 100-U/mL heparin in normal saline 0.9% after each catheter use. Complications occurred in 36% of the patients and the incidence of thrombophlebitis was 8% and only 4% in the control group. In the normal saline group there was a significant increase in total complications and obstruction together with thrombophlebitis as compared with the control group. Kaplan-Meier curves demonstrate that the control group had a significantly higher proportion of catheters without complications. The use of normal saline solutions in post-operative patients thus should be avoided for catheter maintenance. In patients receiving low molecular weight heparin, no intravenous flushing should be used for preventing catheter obstruction or thrombophlebitis in order to reduce costs and nursing workload.
Article
Von Willebrand factor (VWF) is a large multimeric glycoprotein produced in endothelial cells and megakaryocytes and present in subendothelial matrix, blood plasma and platelets. VWF mediates adhesion and aggregation of platelets at sites of vascular injury, processes that are critical for both haemostasis and thrombosis. Thrombus formation involves complex events that are influenced by different environmental conditions. Progress in understanding the structure and function of VWF and the mechanisms that underlie its interactions with platelets has led to important insight into the differentiation between normal haemostasis and pathological arterial thrombosis. The conventional view of signalling-induced platelet aggregation has recently been extended to include activation-independent aggregation. A novel mechanism has been demonstrated for initiating thrombus formation under high haemodynamic forces that involves alpha(IIb)beta(3)-independent platelet aggregation at the interface between immobilised and soluble VWF. This VWF-mediated process may be a key determinant of platelet accumulation in stenotic arteries leading to acute thrombotic occlusion.