Fibrinolytic properties of lysine-derivatized polyethylene in contact with flowing whole blood (Chandler loop model)

2007 ◽  
Vol 81A (3) ◽  
pp. 644-651 ◽  
Author(s):  
W.G. McClung ◽  
D.E. Babcock ◽  
J.L. Brash
Keyword(s):  
Whole Blood ◽  
Loop Model ◽  
Chandler Loop

scholarly journals Bioengineering of Improved Biomaterials Coatings for Extracorporeal Circulation Requires Extended Observation of Blood-Biomaterial Interaction under Flow

2007 ◽  
Vol 2007 ◽  
pp. 1-10 ◽  
Author(s):  
Kris N. J. Stevens ◽  
Yvette B. J. Aldenhoff ◽  
Frederik H. van der Veen ◽  
Jos G. Maessen ◽  
Leo H. Koole
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Thrombus Formation ◽  
Blood Parameters ◽  
Systematic Evaluation ◽  
Loop Model ◽  
Biomaterial Surfaces ◽  
Chandler Loop ◽  
Scanning Electron

Extended use of cardiopulmonary bypass (CPB) systems is often hampered by thrombus formation and infection. Part of these problems relates to imperfect hemocompatibility of the CPB circuitry. The engineering of biomaterial surfaces with genuine long-term hemocompatibility is essentially virgin territory in biomaterials science. For example, most experiments with the well-known Chandler loop model, for evaluation of blood-biomaterial interactions under flow, have been described for a maximum duration of 2 hours only. This study reports a systematic evaluation of two commercial CPB tubings, each with a hemocompatible coating, and one uncoated control. The experiments comprised (i) testing over 5 hours under flow, with human whole blood from 4 different donors; (ii) measurement of essential blood parameters of hemocompatibility; (iii) analysis of the luminal surfaces by scanning electron microscopy and thrombin generation time measurements. The dataset indicated differences in hemocompatibility of the tubings. Furthermore, it appeared that discrimination between biomaterial coatings can be made only after several hours of blood-biomaterial contact. Platelet counting, myeloperoxidase quantification, and scanning electron microscopy proved to be the most useful methods. These findings are believed to be relevant with respect to the bioengineering of extracorporeal devices that should function in contact with blood for extended time.

Thrombi Formed in a Chandler Loop Mimic Human Arterial Thrombi in Structure and PAI-1 Content and Distribution

1997 ◽  
Vol 77 (03) ◽  
pp. 510-515 ◽  
Author(s):  
Linda A Robbie ◽  
Simon P Young ◽  
Bruce Bennett ◽  
Nuala A Booth
Keyword(s):  
Whole Blood ◽  
Closed Loop ◽  
Model System ◽  
Positive Staining ◽  
Blood Clots ◽  
Chandler Loop ◽  
Static Conditions ◽  
Pai 1 ◽  
Striking Contrast

SummaryWe have previously shown that whole blood clots prepared under static conditions are a poor model for human thrombi formed in vivo. The most striking contrast is in the PAI-1 content, some 100 times lower in static clots than in human thrombi. This study aimed to evaluate thrombi formed in an artificial circulation (Chandler loop) using whole blood augmented with platelets. Citrated blood was recalcified and placed in tubing, which was sealed to form a closed loop and circulated. Immunohistochemical staining revealed morphology very similar to human thrombi formed in vivo, comprising dense platelet-rich heads and fibrin-rich tails. Strong positive staining for PAI-1 was observed in fibrin-rich areas of both the head and the tail. The PAI-1 content of the thrombi increased significantly on augmentation of blood with isolated platelets, and reached levels comparable with those in human thrombi. These Chandler thrombi thus provide an appropriate model system for the study of thrombus lysis, in contrast to static blood clots.

Dissolution Of Thrombi By Tissue Plasminogen Activator, Urokinase And Streptokinase In An Artificial Circulating System

1981 ◽  
Author(s):  
C Mattsson ◽  
V Nyberg-Arrhenius ◽  
P Wallén
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Whole Blood ◽  
Porcine Tissue ◽  
Molar Basis ◽  
Blood Clots ◽  
Tissue Plasminogen ◽  
Chandler Loop ◽  
Dose Dependent ◽  
No Activation

The ability of porcine tissue plasminogen activator, urokinase and streptokinase to dissolve whole blood clots has been compared in an artificial circulating system, the Chandler loop. On a molar basis the tissue activator was more effective in lysing both partially and totally cross- linked thrombi than urokinase or streptokinase. The latter drugs required 30–50 times higher concentrations to achieve a fibrinolytic response, similar to that of tissue activator. As demonstrated by analysis of fibrinogen, α2-anti- plasmin and plasmin-α2-antiplasmin complex there was no activation of plasminogen in plasma by the tissue activator in the absence of fibrin. Both urokinase and streptokinase gave under the same conditions rise to a significant dose dependent fibrinogenolysis. In the presence of fibrin, tissue activator induced a weak fibrinogenolysis (about 20 per cent) in plasma, whereas both urokinase and streptokinase caused a much higher degree of fibrinogenolysis (50 and 60 per cent respectively)

scholarly journals 853 Profiling of donor-specific immune effector signatures in response to rituximab in a human whole blood loop assay using blood from CLL patients

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A906-A906
Author(s):  
Mohamed Eltahir ◽  
Erika Fletcher ◽  
Linn Dynesius ◽  
Justina Jarblad ◽  
Martin Lord ◽  
...  
Keyword(s):  
B Cell ◽  
Whole Blood ◽  
Ex Vivo ◽  
Cell Depletion ◽  
Study Patient ◽  
Patient Specific ◽  
List Type ◽  
Loop Model ◽  
B Cell Depletion ◽  
Human Whole Blood

BackgroundRituximab is widely used in the treatment of haematological malignancies, including chronic lymphoid leukaemia (CLL), the most common leukaemia in adults. However, some patients, especially those with high tumour burden, develop cytokine release syndrome (CRS). It is likely that more patients will develop therapy-linked CRS in the future due to the implementation of other immunotherapies, such as CAR T-cell, for many malignancies. Current methods for CRS risk assessment are limited, hence there is a need to develop new methods.MethodsTo better recapitulate an in vivo setting, we implemented the unique human whole blood ‘loop’ system (figure 1)1 to study patient-specific immune responses to rituximab in blood derived from CLL patients.ResultsUpon rituximab infusion, both complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) profiles were evident in CLL patient blood, coincident with CLL cell depletion. Whereas B cell depletion is induced in healthy persons in the blood loop, only patients display B cell depletion coupled with CRS. With the exception of one donor who lacked NK cells, all other five patients displayed variable B cell depletion along with CRS profile. Additionally, inhibition of CDC or ADCC via either inhibitors or antibody Fc modification resulted in skewing of the immune killing mechanism consistent with published literatureAbstract 853 Figure 1Schematic of the blood loop assay. A-C preparation of blood loops, D. Loops are kept in motion by attaching to rotating wheel. The air bubble inside the loop drives blood circulation within the loops.ConclusionsHerein we have shown that the human whole blood loop model can be applied using blood from a specific indication to build a disease-specific CRS and immune activation profiling ex vivo system. Other therapeutic antibodies used for other indications may benefit from antibody characterization in a similar setting.ReferenceFletcher EAK, Eltahir M, Lindqvist F, Rieth J, Törnqvist G, Leja-Jarblad J, Mangsbo SM. Extracorporeal human whole blood in motion, as a tool to predict first-infusion reactions and mechanism-of-action of immunotherapeutics. Int Immunopharmacol 2018 Jan;54:1-11.

scholarly journals Blood Compatibility of Widely used Central Venous Catheters; an Experimental Study

2021 ◽  
Author(s):  
Hulda Thorarinsdottir ◽  
Thomas Kander ◽  
Dorota Johansson ◽  
Bo Nilsson ◽  
Bengt Klarin ◽  
...  
Keyword(s):  
Blood Compatibility ◽  
Thrombus Formation ◽  
Venous Catheter ◽  
Host Defence ◽  
Loop Model ◽  
Central Venous ◽  
Cell Counts ◽  
Chandler Loop ◽  
The Impact ◽  
The Complement System

Abstract Background: An inserted central venous catheter (CVC) is considered foreign material by the inert host defence systems and induce inflammation and thrombus formation. The objective of this study was to evaluate blood compatibility of six commonly used CVCs.Methods: Three coated and three uncoated CVC materials were tested in a modified Chandler loop model. Each catheter material circulated in blood from ten different healthy volunteers for 1 hour. Blood cell counts and measurements of the inert host defence systems were performed on blood samples from the loop.Results: All the tested catheters demonstrated impact on blood cells, contact coagulation, the complement system, or inflammatory markers, although the impact varied significantly.Conclusions: Of the catheters we evaluated, the most unfavourable blood compatibility profile was found for the polyurethane CVC coated with chlorohexidine and silver sulfadiazine. The greatest variation in blood compatibility between test runs was noted for the silicone dialysis catheter. Poor blood compatibility should be taken seriously but given the experimental design of the current study the clinical significance remains to be evaluated.

PVC-plasticizer DEHP in medical products: do thin coatings really reduce DEHP leaching into blood?

Perfusion ◽  
2005 ◽  
Vol 20 (6) ◽  
pp. 351-357 ◽  
Author(s):  
Sibylle L Hildenbrand ◽  
Hans-Dieter Lehmann ◽  
Roman Wodarz ◽  
Gerhard Ziemer ◽  
Hans P Wendel
Keyword(s):  
Blood Circulation ◽  
Surface Coatings ◽  
Oxidation Products ◽  
Loop Model ◽  
Thin Coatings ◽  
Plasticized Pvc ◽  
Human Fertility ◽  
Chandler Loop ◽  
Extracorporeal Blood Circulation ◽  
Ethylhexyl Phthalate

The hemocompatibility of artificial surfaces in extracorporeal blood circulation systems can be improved by coatings. According to the literature, heparin coatings should avoid the leaching of the plasticizer di(2-ethylhexyl) phthalate (DEHP) into the blood from components made from plasticized polyvinyl chloride (PVC). DEHP and its metabolites are known to impair the fertility of male rodents; effects on human fertility are assumed. Three different surface coatings with and without heparin were examined in a Chandler Loop model at 37°C using fresh human blood to evaluate their hemocompatibility and barrier property to plasticizer. The levels of toxic oxidation products of DEHP generated in the blood, particularly, were found as high as in the uncoated tubing. The coatings improved the hemocompatibility, but are not safe protection against the hazardous metabolites of DEHP. For pregnant women, neonates and children, we would recommend using the available surface-coated plasticized PVC tubing sets, but free of DEHP.

Fine Structure of Platelet Interaction with a New Microcrystalline Collagen Preparation

1974 ◽  
Vol 32 ◽  
pp. 58-59
Author(s):  
W. H. Zucker ◽  
R. G. Mason
Keyword(s):  
Fine Structure ◽  
Platelet Aggregation ◽  
Hydrochloric Acid ◽  
Whole Blood ◽  
Platelet Adhesion ◽  
Hemostatic Agent ◽  
Native Collagen ◽  
Fibrillar Morphology ◽  
Clinical Interest ◽  
New Form

Platelet adhesion initiates platelet aggregation and is an important component of the hemostatic process. Since the development of a new form of collagen as a topical hemostatic agent is of both basic and clinical interest, an ultrastructural and hematologic study of the interaction of platelets with the microcrystalline collagen preparation was undertaken.In this study, whole blood anticoagulated with EDTA was used in order to inhibit aggregation and permit study of platelet adhesion to collagen as an isolated event. The microcrystalline collagen was prepared from bovine dermal corium; milling was with sharp blades. The preparation consists of partial hydrochloric acid amine collagen salts and retains much of the fibrillar morphology of native collagen.

3-D organization of fibrinogen receptors using computer reconstruction and whole-mount microscopy

1988 ◽  
Vol 46 ◽  
pp. 30-31
Author(s):  
E. T. O'Toole ◽  
R. R. Hantgan ◽  
J. C. Lewis
Keyword(s):  
Whole Blood ◽  
Colloidal Gold ◽  
Blood Platelets ◽  
Cell Contact ◽  
Computer Assisted ◽  
Adherent Cells ◽  
Differential Centrifugation ◽  
Computer Reconstruction ◽  
Sds Page ◽  
Whole Mount

Thrombocytes (TC), the avian equivalent of blood platelets, support hemostasis by aggregating at sites of injury. Studies in our lab suggested that fibrinogen (fib) is a requisite cofactor for TC aggregation but operates by an undefined mechanism. To study the interaction of fib with TC and to identify fib receptors on cells, fib was purified from pigeon plasma, conjugated to colloidal gold and used both to facilitate aggregation and as a receptor probe. Described is the application of computer assisted reconstruction and stereo whole mount microscopy to visualize the 3-D organization of fib receptors at sites of cell contact in TC aggregates and on adherent cells.Pigeon TC were obtained from citrated whole blood by differential centrifugation, washed with Ca++ free Hank's balanced salts containing 0.3% EDTA (pH 6.5) and resuspended in Ca++ free Hank's. Pigeon fib was isolated by precipitation with PEG-1000 and the purity assessed by SDS-PAGE. Fib was conjugated to 25nm colloidal gold by vortexing and the conjugates used as the ligand to identify fib receptors.

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