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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1994-11-7
pubmed:abstractText
Synthetic vascular prostheses lack the uniquely low thrombogenicity provided by the endothelial cell lining of autogenous saphenous vein or artery grafts. The thrombogenic nature of the synthetic graft surface becomes a major determinant of early prosthetic graft patency. We demonstrate in a baboon ex vivo synthetic graft model that modification of the host's platelet interaction with the graft surface results in inhibition of platelet thrombus formation and thereby, a possible enhancement of early prosthetic graft patency. This was achieved by selective blockage of the platelet alpha IIb beta 3 receptor by the arginine-glycine-aspartic acid-containing synthetic peptide TP9201. Platelet thrombus formation on a Dacron graft indicated by accumulation of indium III-oxine-labeled autologous platelets was measured by gamma camera imaging. After 60 minutes of circulation, TP9201 at a bolus of 125 micrograms/kg; infusion of 3 micrograms/kg/min, bolus of 190 micrograms/kg; infusion of 5 micrograms/kg/min, bolus of 250 micrograms/kg; infusion of 6 micrograms/kg/min, and bolus of 500 micrograms/kg; infusion of 12 micrograms/kg/min decreased platelet uptake on the graft to 50%, 40%, 30%, and 10% of control uptake, respectively. Forelimb template bleeding times were not found to be significantly prolonged at doses that effectively inhibit ex vivo platelet aggregation. As a result of drug treatment, no changes in hemodynamic parameters or hematologic profile, including platelet number and clotting time, were observed. We demonstrate here that the arginine-glycine-aspartic acid-containing peptide TP9201, which competitively inhibits the alpha IIb beta 3 integrin-fibrinogen interaction, significantly decreased the accumulation of platelets on a Dacron vascular graft. Molecules like peptide TP9201, because of its unique activity profile, may represent a superior approach to the control of platelet accumulation on thrombogenic surfaces.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2143
pubmed:author
pubmed:issnType
Print
pubmed:volume
124
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
589-99
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Selective alpha IIb beta 3 receptor blockage with peptide TP9201 prevents platelet uptake on Dacron vascular grafts without significant effect on bleeding time.
pubmed:affiliation
Surgical Research Laboratory, New England Medical Center, Boston.
pubmed:publicationType
Journal Article