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Coagulation, fibrinolysis and cell activation in patients and shed mediastinal blood during coronary artery bypass grafting using a new heparin-coated surface
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Clinical chemisrty, coagulation research)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. (Immunology)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. (Immunology)
(Clinical chemistry)
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2002 (English)In: Journal of Thoracic and Cardiovascular Surgery, ISSN 0022-5223, E-ISSN 1097-685X, Vol. 124, no 2, 321-332 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Heparin coating of the cardiopulmonary bypass circuit is shown to improve the biocompatibility of the surface. We have studied a new heparin surface, the Corline Heparin Surface, applied to a complete set of an extracorporeal device used during coronary artery bypass grafting in terms of activation of inflammation, coagulation, and fibrinolysis in patients and in shed mediastinal blood.

METHODS: Sixty patients scheduled for coronary artery bypass grafting were randomized to one of 3 groups with heparin-coated devices receiving either a standard, high, or low dose of systemic heparin or to an uncoated but otherwise identical circuit receiving a standard dose of systemic heparin. Samples were drawn before, during, and after the operation from the pericardial cavity and in shed mediastinal blood. No autotransfusion of shed mediastinal blood was performed.

RESULTS: The Corline Heparin Surface significantly reduced the activation of coagulation, fibrinolysis, platelets, and inflammation compared with that seen with the uncoated surface in combination with a standard dose of systemic heparin during cardiac surgery with cardiopulmonary bypass. Both a decrease and an increase of systemic heparin in combination with the coated heparin surface resulted in higher activation of these processes. A significantly higher expression of all studied parameters was found in the shed mediastinal blood compared with in systemic blood at the same time.

CONCLUSIONS: The Corline Heparin Surface used in cardiopulmonary bypass proved to be more biocompatible than an uncoated surface when using a standard systemic heparin dose. The low dose of systemic heparin might not be sufficient to maintain the antithrombotic activity, and the high dose resulted in direct cell activation rather than a further anti-inflammatory and anticoagulatory effect.

Place, publisher, year, edition, pages
2002. Vol. 124, no 2, 321-332 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-91003DOI: 10.1067/mtc.2002.122551PubMedID: 12167793OAI: oai:DiVA.org:uu-91003DiVA: diva2:163565
Available from: 2003-10-30 Created: 2003-10-30 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Monocytes, Tissue Factor and Heparin-coated Surfaces: Clinical and Experimental Studies
Open this publication in new window or tab >>Monocytes, Tissue Factor and Heparin-coated Surfaces: Clinical and Experimental Studies
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cardiopulmonary bypass (CPB) is associated with inflammatory response and activation of coagulation. Heparin coating of the CPB circuit is shown to improve the biocompatibility of the surface. The biological effects of a new heparin surface, the Corline Heparin Surface (CHS), prepared according to a new principle, have been studied.

The CHS used during coronary artery bypass grafting with CPB in sixty patients prevented adhesion of cells to the extracorporeal device. The activation of inflammation, coagulation, and fibrinolysis was significantly reduced by the use of CHS. Both a reduced and an increased dose of systemic heparin in combination with the heparin-coated surface resulted in more activation of inflammation and coagulation.

Photoelectron spectroscopy studies of the molecular structure of the CHS demonstrated that a single layer of the heparin surface, equivalent to what was used in the in vivo studies, did not completely cover the substrate surface. Additional layer of immobilized heparin has resulted in a complete coverage. We examined the biological effects, i.e. activation of inflammation and coagulation, by CHS in one and two layers in an in vitro-study. The data from this study clearly demonstrated that a uniform surface coating of the CHS results in only minor activation of coagulation, inflammation and cell activation.

Monocytes do not normally express tissue factor (TF), initiator of the coagulation in vivo, but can be induced upon adhesion to artificial surfaces. TF is receptor for coagulation factor VIIa (FVIIa) and binding subsequently leads to formation of thrombin. Other biological effects beyond coagulation, as inflammation and angiogenesis, has recently been associated with the formation of TF·FVIIa. The TF∙FVIIa signal transduction induced an increased sensitivity to PDGF-BB-stimulated migration and an increased production of IL-8 and TNF-α in monocytes. These could be important mechanisms for continued recruitment of cells to sites of inflammation.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 65 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1299
Keyword
Medicine, monocytes, tissue factor, heparin-coated surfaces, coagulation, inflammation, thrombin, cytokines, cardiopulmonary bypass, biocompatibility, migration, chemotaxis, Medicin
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:uu:diva-3740 (URN)91-554-5779-7 (ISBN)
Public defence
2003-11-21, Robergsalen, ingång 40, Akademiska sjukhuset, Uppsala, 13:15
Opponent
Supervisors
Available from: 2003-10-30 Created: 2003-10-30Bibliographically approved

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Johnell, MatildaElgue, GracielaLarsson, RolfThelin, StefanSiegbahn, Agneta

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Journal of Thoracic and Cardiovascular Surgery
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