Document Detail


Effects of GP IIb/IIIa receptor monoclonal antibody (7E3), heparin, and aspirin in an ex vivo canine arteriovenous shunt model of stent thrombosis.
MedLine Citation:
PMID:  9054765     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Thrombosis is an important limitation of metallic coronary stents, especially in smaller vessels in which shear rates are high. Monoclonal antibody to platelet glycoprotein IIb/IIIa receptor (7E3) has been shown to inhibit shear-induced platelet aggregation. In this study, we compared the effects of 7E3, heparin, and aspirin on stent thrombosis in an ex vivo arteriovenous shunt model of high-shear blood flow.
METHODS AND RESULTS: An ex vivo arteriovenous shunt was created in 10 anesthetized dogs. Control rough-surface slotted-tube nitinol stents (n = 72) expanded to 2 mm in diameter in a tubular perfusion chamber were interposed in the shunt and exposed to flowing arterial blood at a shear rate of 2100s-1 for 20 minutes. The animals were treated with intravenous murine 7E3 (Fab')2 (0.2, 0.4, and 0.8 mg/kg), heparin (100 U/kg), or aspirin (10 mg/kg). Effects of the test agents on thrombus weight, platelet aggregation, platelet P-selectin expression, bleeding time, and activated clotting time (ACT) were quantified. 7E3 reduced stent thrombosis by 95% (20 +/- 1 to 1 +/- 1 mg, P < .001) and platelet aggregation by 94% (14 +/- 2 to 1 +/- 1 omega, P < .001) at the highest dose (0.8 mg/kg). 7E3 significantly prolonged bleeding time but had no effect on ACT and platelet P-selectin expression. Heparin prolonged ACT but had no significant effect on stent thrombosis or platelet aggregation. Aspirin, although it inhibited platelet aggregation by 65%, had no effect on stent thrombosis (19 +/- 2 versus 20 +/- 1 mg in controls).
CONCLUSIONS: 7E3 produced a dose-dependent inhibition of acute stent thrombosis under high-shear flow conditions. Stent thrombosis was resistant to heparin and aspirin. Thus, 7E3 may be an effective agent for preventing stent thrombosis.
Authors:
R R Makkar; F Litvack; N L Eigler; M Nakamura; P A Ivey; J S Forrester; P K Shah; R E Jordan; S Kaul
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  95     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1997 Feb 
Date Detail:
Created Date:  1997-04-03     Completed Date:  1997-04-03     Revised Date:  2013-05-24    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1015-21     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Antibodies, Monoclonal / pharmacology*
Arteriovenous Shunt, Surgical*
Aspirin / pharmacology*
Bleeding Time
Coronary Vessels / drug effects,  pathology*,  ultrastructure
Dogs
Extracorporeal Circulation
Heparin / pharmacology*
Immunoglobulin Fab Fragments / pharmacology*
Microscopy, Electron, Scanning
Platelet Aggregation / drug effects*
Platelet Aggregation Inhibitors / pharmacology*
Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
Stents / adverse effects*
Thrombosis / etiology,  pathology,  prevention & control*
Whole Blood Coagulation Time
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Immunoglobulin Fab Fragments; 0/Platelet Aggregation Inhibitors; 0/Platelet Glycoprotein GPIIb-IIIa Complex; 50-78-2/Aspirin; 9005-49-6/Heparin; X85G7936GV/abciximab

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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