Abstract | INTRODUCTION: MATERIALS AND METHODS: After forming an occlusive thrombus in the right carotid artery (RCA), twenty-one dogs were administered recombinant tissue plasminogen activator (rt-PA) intra-arterially to achieve thrombolysis in the presence of either 0.9% NaCl or Intimatan (9 mg/kg bolus+300 mug/kg/min i.v. infusion). Next, the left carotid arteries (LCA) of the same animals were injured in the presence of either Intimatan or 0.9% NaCl. RESULTS: The incidence of RCA rethrombosis between the Intimatan and control groups was 2/9 and 8/12, respectively. The quality of RCA blood flow, i.e., patency score (Scale of 0-3, i.e., no flow to high flow, respectively), was 2.3+/-0.4 ( Intimatan) versus 0.9+/-0.4 ( 0.9% NaCl). The incidence of primary thrombosis was determined among the groups as 0/9 ( Intimatan) versus 7/12 ( 0.9% NaCl); the patency score was 2.8+/-0.1 ( Intimatan) versus 0.9+/-0.4 ( 0.9% NaCl). Intimatan resulted in a >90% ex vivo inhibition of gamma-thrombin-induced platelet aggregation whereas 0.9% NaCl had no inhibitory effect. Clot-bound thrombin activity was reduced significantly by Intimatan. Intimatan induced <2-fold change in aPTT and bleeding time (BT) when corrected for the 0.9% NaCl group. CONCLUSIONS:
Intimatan significantly reduces the incidence of both primary and secondary arterial thrombosis while maintaining a high-grade vessel patency score with only moderate increases in BT and aPTT.
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Authors | Ting-Ting Hong, Cornelius L Van Gorp, Alan D Cardin, Benedict R Lucchesi |
Journal | Thrombosis research
(Thromb Res)
Vol. 117
Issue 3
Pg. 333-42
( 2006)
ISSN: 0049-3848 [Print] United States |
PMID | 15893368
(Publication Type: Journal Article)
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Chemical References |
- Anticoagulants
- Recombinant Proteins
- intimatan
- Dermatan Sulfate
- Heparin Cofactor II
- Thrombin
- Tissue Plasminogen Activator
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Topics |
- Animals
- Anticoagulants
(pharmacology)
- Arteries
(injuries, pathology)
- Bleeding Time
- Blood Coagulation
- Blood Platelets
(metabolism)
- Dermatan Sulfate
(analogs & derivatives, pharmacology)
- Disease Models, Animal
- Dogs
- Dose-Response Relationship, Drug
- Female
- Heparin Cofactor II
(agonists)
- Male
- Models, Chemical
- Platelet Aggregation
- Prothrombin Time
- Recombinant Proteins
(pharmacology)
- Thrombin
(antagonists & inhibitors, chemistry)
- Thrombolytic Therapy
- Thrombosis
(drug therapy, prevention & control)
- Time Factors
- Tissue Plasminogen Activator
(pharmacology)
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