| Efficacy of local inhibition of procoagulant activity associated with small-diameter prosthetic vascular grafts. | |
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MedLine Citation:
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PMID: 8911411 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Graft procoagulant activity is determined by thrombin (IIa) and activated factor X (Xa) that binds to thrombus. Thrombus-associated factor Xa and thrombin are resistant to antithrombin III-dependent therapy (heparin). To avoid complications and costs associated with systemic administration, we evaluated whether locally applied antithrombotic agents inhibit prosthetic graft procoagulant activity under no-flow and low-flow conditions. METHODS: Four-millimeter-diameter collagen-coated grafts were preclotted in recalcified human plasma, washed, immersed in antithrombotic agents (either 100 nm hirudin, 20 microns D-Phe-L-Pro-L-Arg chloromethylketone, 5 microns tick anticoagulant peptide or 5 or 10 micrograms/ml tissue factor pathway inhibitor) or saline solution, and extensively rewashed. Grafts were exposed to recalcified plasma either in multiwell plates or underwent perfusion at 1 ml/min flow rate. Fibrinopeptide A, which reflects fibrin elaboration, was measured as a marker of thrombin activity. RESULTS: Inhibitors reduced fibrinopeptide generation at 8 minutes by 55% (tissue factor pathway inhibitor), 57% (hirudin), or 63% (tick anticoagulant peptide and D-Phe-L-Pro-L-Argchloromethylketone) compared with the control agents (p < 0.05). Under low-flow conditions tissue factor pathway inhibitor and hirudin reduced fibrinopeptide generation at 13 minutes by 61% and 49%, respectively, when compared with control agents (p < 0.05). CONCLUSIONS: Graft-associated inhibitors targeted at factors IIa, Xa, or tissue factor/VIIa/Xa complex effectively reduce procoagulant activity on prosthetic grafts. The success of local application of antithrombotic agents in attenuating early fibrin formation suggests that this strategy could favorably influence acute graft patency, and we speculate these agents may improve long-term graft patency as well. |
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Authors:
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L Oltrona; P R Eisenberg; D R Abendschein; B G Rubin |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of vascular surgery : official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter Volume: 24 ISSN: 0741-5214 ISO Abbreviation: J. Vasc. Surg. Publication Date: 1996 Oct |
Date Detail:
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Created Date: 1996-12-11 Completed Date: 1996-12-11 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8407742 Medline TA: J Vasc Surg Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 624-31 Citation Subset: IM |
Affiliation:
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Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Chloromethyl Ketones
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pharmacology Blood Coagulation* / drug effects Blood Vessel Prosthesis* Factor Xa / antagonists & inhibitors Fibrin / metabolism Fibrinolytic Agents / pharmacology* Fibrinopeptide A / metabolism Hirudins / pharmacology Humans Lipoproteins / pharmacology Peptides / pharmacology Thrombin / antagonists & inhibitors |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Chloromethyl Ketones; 0/Fibrinolytic Agents; 0/Hirudins; 0/Lipoproteins; 0/Peptides; 0/lipoprotein-associated coagulation inhibitor; 0/tick anticoagulant peptide; 25422-31-5/Fibrinopeptide A; 65149-23-7/phenylalanyl-prolyl-arginine-chloromethyl ketone; 9001-31-4/Fibrin; EC 3.4.21.5/Thrombin; EC 3.4.21.6/Factor Xa |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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