Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
|
pubmed:dateCreated |
1992-5-14
|
pubmed:abstractText |
Platelet adhesion and aggregation are mediated by fibrinogen via the receptor glycoprotein IIb/IIIa, which recognizes the arginine-glycine-aspartic (RGD) amino-acid sequence. We investigated the ability of 8-guanidino-octanoyl-Asp-Phe (SC-49992), an intravenously infused, stable RGD analogue, to inhibit human platelet function in vitro and to reduce in vivo canine platelet deposition on prosthetic grafts. Human platelet aggregation induced by 10 mumol/L adenosine diphosphate was inhibited in a concentration dependent manner with an ED50 of 1 microgram/ml of SC-49992. Adenosine diphosphate-induced secretion, which is dependent on fibrinogen occupancy of the glycoprotein IIb/IIIa receptor, was reduced in a concentration dependent manner, also with an ED50 of 1 microgram/ml. Thrombin-induced secretion, which is independent of fibrinogen binding, was unaffected. Activation-dependent platelet adhesion to fibrinogen substrates was reduced in a concentration-dependent manner by SC-49992. Platelet adhesion to fibronectin substrates was also reduced by the analogue, but to a lesser extent. SC-49992 effectively eluted glycoprotein IIb/IIIa bound to RGD derivatized sepharose. Eight thrombosis-prone dogs had polytetrafluoroethylene femoral artery grafts placed. Dogs received the RGD analogue or a normal saline infusion during their first graft procedure. One week later a second contralateral femoral graft with infusion of the other agent was performed. Aggregometry during RGD analogue infusion demonstrated inhibition of induced aggregation, whereas normal saline infusion had no effect. As measured by the adherence of platelets labeled with indium III 8-guanidino-octanoyl-Asp-Phe reduced platelet deposition on vascular grafts by more than 90% (p = 0.0006, log transformed data, paired t test.(ABSTRACT TRUNCATED AT 250 WORDS)
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Apr
|
pubmed:issn |
0741-5214
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
15
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
683-91; discussion 691-2
|
pubmed:dateRevised |
2006-11-15
|
pubmed:meshHeading |
pubmed-meshheading:1560559-Amino Acid Sequence,
pubmed-meshheading:1560559-Animals,
pubmed-meshheading:1560559-Blood Platelets,
pubmed-meshheading:1560559-Blood Vessel Prosthesis,
pubmed-meshheading:1560559-Dipeptides,
pubmed-meshheading:1560559-Dogs,
pubmed-meshheading:1560559-Humans,
pubmed-meshheading:1560559-Molecular Sequence Data,
pubmed-meshheading:1560559-Platelet Adhesiveness,
pubmed-meshheading:1560559-Platelet Aggregation,
pubmed-meshheading:1560559-Platelet Aggregation Inhibitors
|
pubmed:year |
1992
|
pubmed:articleTitle |
New RGD analogue inhibits human platelet adhesion and aggregation and eliminates platelet deposition on canine vascular grafts.
|
pubmed:affiliation |
Department of Surgery, Washington University School of Medicine, St. Louis, MO.
|
pubmed:publicationType |
Journal Article,
In Vitro
|