Intimatan (dermatan 4,6-O-disulfate) prevents rethrombosis after successful thrombolysis in the canine model of deep vessel wall injury.
Thromb Res
; 117(3): 333-42, 2006.
Article
em En
| MEDLINE
| ID: mdl-15893368
ABSTRACT
INTRODUCTION:
Intimatan (dermatan 4,6-O-disulfate), a heparin cofactor II (HCII) agonist, inhibits both the fluid phase and thrombus bound thrombin. The efficacy of Intimatan as an adjunctive anticoagulant during thrombolysis was evaluated in the canine model of arterial injury. MATERIALS ANDMETHODS:
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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Base de dados:
MEDLINE
Assunto principal:
Trombose
/
Dermatan Sulfato
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article