Abstract | BACKGROUND: METHODS AND RESULTS:
Thrombus formation was measured by quantitative imaging of 111In-labeled platelet deposition on segments of thrombogenic vascular graft interposed in arteriovenous shunts in a porcine model. Intravenous administration of PPACK inhibited platelet deposition at a dose of 12.5 micrograms/kg per minute, which was associated with significant prolongations of both template bleeding times and activated partial thromboplastin times. By contrast, local infusion of PPACK at a dose of 0.02 micrograms/kg per minute (ie, a 600-fold smaller dose) into the fluid boundary layer at the interface between flowing blood and the thrombogenic segment produced equivalent inhibition of platelet deposition without prolonging either the bleeding time or the activated partial thromboplastin time. In addition, static exposure of a mural thrombus to solutions of PPACK at concentrations > or = 2.5 mg/mL for 15 minutes produced sustained inhibition of platelet-dependent thrombosis with no change in hemostatic measurements. CONCLUSIONS: These results indicate that local delivery of the direct antithrombin PPACK, by either boundary layer infusion or static application techniques, effectively inhibits platelet-dependent thrombosis at doses that are several orders of magnitude less than the systemic dose required for an equivalent antithrombotic effect. In contrast to the systemic administration of PPACK, local delivery produced maximal inhibition of thrombosis without alterations in hemostasis.
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Authors | N A Scott, G L Nunes, S B King 3rd, L A Harker, S R Hanson |
Journal | Circulation
(Circulation)
Vol. 90
Issue 4
Pg. 1951-5
(Oct 1994)
ISSN: 0009-7322 [Print] United States |
PMID | 7923684
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Amino Acid Chloromethyl Ketones
- Antithrombins
- Polyethylene Terephthalates
- phenylalanyl-prolyl-arginine-chloromethyl ketone
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Topics |
- Amino Acid Chloromethyl Ketones
(administration & dosage, pharmacology)
- Animals
- Antithrombins
(administration & dosage, pharmacology)
- Blood Platelets
(drug effects, physiology)
- Blood Vessel Prosthesis
- Coronary Thrombosis
(prevention & control)
- Dose-Response Relationship, Drug
- Hemostasis
(drug effects)
- Injections, Intravenous
- Polyethylene Terephthalates
- Swine
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