Recombinant Leech Antiplatelet Protein Prevents Collagen‐Mediated Platelet Aggregation but Not Collagen Graft Thrombosis in Baboons
作者:
Linda Schaffer,
John Davidson,
Peter Siegl,
Robert Gould,
Ruth Nutt,
Stephen Brady,
Thomas Connolly,
期刊:
Arteriosclerosis and Thrombosis: A Journal of Vascular Biology
(OVID Available online 1993)
卷期:
Volume 13,
issue 11
页码: 1593-1601
ISSN:1049-8834
年代: 1993
出版商: OVID
关键词: collagen inhibitor;LAPP;baboon model of thrombosis;platelets;fibrinogen receptor antagonist
数据来源: OVID
摘要:
Leech antiplatelet protein (LAPP) is a specific inhibitor of collagen-induced human platelet aggregation and adhesion to collagen under static conditions. Recombinant LAPP (rLAPP) and L-366,763 (acetylated- Cys-Asn-Pro-Arg-Gly-Asp-Cys-NH2), a peptidyl fibrinogen receptor antagonist, were evaluated in an anesthetized baboon thrombosis model using a collagen-coated graft segment of an arteriovenous shunt to elicit thrombus formation. Animals were randomized to receive systemic intravenous administration of rLAPP (100 fig • kg"1• min"1; n=5), L-366,763 (8.5 /tg • kg"1• min"1; n=3), or saline (n=3). Despite complete and selective inhibition of type I collagen-induced ex vivo aggregation of platelets, rLAPP had no significant effect on the rate or the extent of '"In-labeled platelet deposition onto the collagen graft and no effect on template bleeding time. In contrast, L-366,763 completely prevented platelet deposition, maintained blood flow, and significantly prolonged bleeding time at the dosage that inhibited ex vivo aggregation in response to all agonists studied. In this study, the absence of an antithrombotic benefit of rLAPP contrasted sharply with the efficacy of the fibrinogen receptor antagonist. These results demonstrate that specific inhibition of collagen-mediated platelet aggregation alone is not sufficient to prevent platelet-dependent thrombosis in this baboon model.
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