Enhanced thrombolysis by a factor XIIIa inhibitor in a rabbit model of femoral artery thrombosis.
Thromb Res
; 59(1): 15-26, 1990 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-1975957
ABSTRACT
Factor XIIIa (FXIIIa) catalyzes covalent crosslinking reactions of fibrin, affording the clot additional structural stability and resistance to plasmin-mediated degradation. Thus, inhibition of FXIIIa may render thrombi more susceptible to tissue-plasminogen activator (t-PA)-induced thrombolysis in vivo. We therefore examined thrombus weight and time to lysis in anesthetized rabbits undergoing arterial thrombosis produced by insertion of a copper coil into the lumen of the right femoral artery. The effects of t-PA alone (started 30 min after coil insertion) or in combination with a FXIIIa inhibitor (L722151) started 15 min before, 8 min after or 20 min after coil insertion were determined. Although t-PA alone (2 mg/kg over 2 hrs) lowered thrombus weight significantly, there was no evidence of flow restoration. Addition of L722151 to t-PA before, or 8 min after coil insertion, further lowered thrombus weights and produced thrombolysis in 50% of the animals. This beneficial effect was lost when L722151 administration was delayed until 20 min after thrombus formation, suggesting that the type(s) of crosslinking inhibited by L722151 was complete by this time. Infusion of L722151 alone had no significant effect on thrombus weight. These results demonstrate a time-dependent facilitation of t-PA-induced arterial thrombolysis by FXIIIa inhibition in a small animal model.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiadiazóis
/
Trombose
/
Terapia Trombolítica
/
Transglutaminases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Thromb Res
Ano de publicação:
1990
Tipo de documento:
Article