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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-11-22
pubmed:abstractText
Thrombostatin (RPPGF), an angiotensin converting enzyme metabolite of bradykinin, is an inhibitor of alpha-thrombin's ability to activate platelets. We examined the in vivo pharmacokinetics and pharmacodynamics of thrombostatin in rabbits and its ability to inhibit coronary thrombosis induced by electrolytic injury in dogs. Plasma half-life of thrombostatin had a t1/2alpha of 2.6 min and a t1/2beta of 24 min in rabbits. Ligating the renal arteries did not prolong clearance (t1/2alpha = 2.4 min; t1/2beta = 12 min). Thrombostatin produced a prolonged in vivo antiplatelet effect. At 30 min after a single intravenous administration in rabbits, thrombostatin's plasma concentration was <8.7 microM (5 microg/ml). However, ex vivo 20 and 40 nM gamma-thrombin-induced platelet aggregation of these rabbits' platelets was inhibited 40% for 2.75 and 1 h, respectively. In vitro, flow cytometry studies revealed that thrombostatin specifically bound to human platelets and washed human platelets treated with thrombostatin were less responsive to gamma-thrombin than control platelets. Using electrolytic injury to induce coronary artery thrombosis, dogs treated with thrombostatin, aspirin, or combined thrombostatin and aspirin occluded in 62+/-25 (mean +/- SD), 62+/-36, or 89+/-32 min versus untreated animals which occluded at 39+/-27 min, (p<0.01, p<0.01 and p<0.001, respectively). These studies show that thrombostatin binds to platelets and can delay coronary occlusion in vivo.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0340-6245
pubmed:author
pubmed:issnType
Print
pubmed:volume
82
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1182-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Thrombostatin inhibits induced canine coronary thrombosis.
pubmed:affiliation
Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0640, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't