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Effects on blood compatibility in vitro by combining a direct P2Y(12) receptor inhibitor and heparin coating of stents
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
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2006 (English)In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 17, no 5, 318-327 p.Article in journal (Refereed) Published
Abstract [en]

The effect of the direct platelet P2Y12 receptor inhibitor, AR-C69931MX, on activation of blood induced by stents with and without heparin coating was investigated using a whole blood Chandler loop model in vitro . Stents were deployed in Chandler loops. Fresh human blood with heparin and AR-C69931MX was rotated for 1 h at 37°C and used for measurements of platelets, microparticles, thrombin-antithrombin complex (TAT), fibrinogen binding to platelets, P-selectin expression by platelets, CD11b, Prothrombin Fragment F1+2, FXIa-AT, FXIIa-AT, C3a, sC5b-9 and stent score. In the first experiment there were four study groups with unmodified stents: 1a, no AR-C69931MX; 1b, 250 nmol/L; 1c, 750 nmol/L; 1d, 2250 nmol/L of AR-C69931MX. In the second experiment the concentration of AR-C69931MX was 500 nmol/L: 2a; tubings without stent; 2b; tubings with heparin-coated stent; 2c; tubings with unmodified stents. Heparin-coated stents were used in the third experiment: 3a; no AR-C69931MX; 3b; 500 nmol/L of AR-C69931MX. In the first experiment there were significant differences in all parameters analysed except for C3a, and stent score when the group with no AR-C69931MX was compared to all the groups with AR-C69931MX. In the second experiment there were significant differences in platelet count, TAT, FXIa-AT, FXIIa-AT and stent score when unmodified stents were compared to loops with no stents and partly to loops with heparin-coated stents. In the third experiment there was a significant reduction in generation of TAT, stent score and better preservation of platelet number by combining the platelet inhibitor and heparin-coated stents as compared to heparin-coated stents alone. The conclusion is that the direct P2Y12 receptor inhibitor AR-C69931MX reduced the different aspects of activation of blood induced by both unmodified and heparin-coated stents.

Place, publisher, year, edition, pages
2006. Vol. 17, no 5, 318-327 p.
Keyword [en]
Heparin coating, Platelets, Purin receptor blockade, Stents
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-95970DOI: 10.1080/09537100600746557ISI: 000239976000008PubMedID: 16928604OAI: oai:DiVA.org:uu-95970DiVA: diva2:170367
Available from: 2007-05-25 Created: 2007-05-25 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Platelet Activation and Inhibition in Connection with Vascular Stents
Open this publication in new window or tab >>Platelet Activation and Inhibition in Connection with Vascular Stents
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis describes the Chandler loop, which makes it possible to conduct studies in vitro of molecular and cellular interactions between whole blood and stents. It was possible to monitor activation and inhibition of the cascades systems, leukocytes and platelets by combining different platelet inhibitors and heparin coating of stents. The clinical study was performed on patients with ACS undergoing PCI and stent implantation. In this study platelet activation markers P-selectin, and αIIb/β3 as well as inflammatory markers were followed from baseline during the first 48 hours post-PCI. The same parameters were evaluated in healthy controls for comparison at baseline.

In vitro: The activation of blood in the Chandler loops were more pronounced for unmodified stent grafts than for partially heparin coated stent grafts. Heparin coated stent grafts dreated the same activation as the loops alone. This indicated that the Chandler loop system was a feasible tool for evaluation of blood compability of stents.

Heparin coating of stents significantly reduced TAT, CD11b and platelet activation. The combination of a heparin coated stent and abciximab reduced TAT and contact activation, as compared to abciximab or heparin coating alone.

Heparin coating of stents in combination with AR-C69931MX resulted in a significant reduction in TAT and preservation of the platelet count but had no effect on contact activation.

Clinical study: Abciximab resulted in an almost total inhibition of fibrinogen binding to platelets and persisted throughout the observation period. Clopidogrel effectscould be observed at four hours but was more pronounced at 24 hours.

P-selectin expression did not differ over time between groups, indicating that platelet activation with α-granule secretion was not affected by abciximab treatment.

The hs-CRP, C3a and sC5b-9 levels increased 24 to 48 hours after PCI in patients with ACS. FXIIa-C1inh was reduced in ACS patients receiving abciximab as compared to controls. The elevated bFGF levels at baseline returned to the levels observed in controls four hours after PCI and stent implantation, whereas an increase in VEGF was observed 24 hours post-PCI.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 98 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 266
Keyword
Medicine, platelets, inhibition, activation, stents, ACS, Medicin
Identifiers
urn:nbn:se:uu:diva-7918 (URN)978-91-554-6912-2 (ISBN)
Public defence
2007-06-02, Rudbeckssalen, Rudbecklaboratoriet, Akademiska Sjukhuset, Uppsala, 08:45
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Available from: 2007-05-25 Created: 2007-05-25Bibliographically approved

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Larsson, RolfElgue, GracielaLarsson, Anders

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