A thrombosis model for evaluating thrombolytic agents in the guinea-pig: comparison of t-PA, scu-PA and a novel thrombolytic agent, staphylokinase, on thrombolytic activity.
We have studied three fibrin-specific thrombolytic agents in a photochemically-induced, guinea-pig femoral artery model of thrombosis. Tissue-type plasminogen activator (t-PA, 0.3 and 1 mg/kg), single-chain urokinase-type plasminogen activator (scu-PA,5 and 15 mg/kg) and a novel thrombolytic agent, staphylokinase (SAK, 0.3 and 1 mg/kg) were intravenously infused for 30 min after arterial occlusion by a photochemically-induced reaction between rose bengal and light (540 nm). These thrombolytic agents induced thrombolysis in 17-66% of animals and 24 h later, reocclusion occurred in 75-100%. t-PA hardly altered plasma fibrinogen throughout the experimental period. In contrast, scu-PA (15 mg/kg) decreased plasma fibrinogen and alpha 2-antiplasmin levels by 25% and 90% respectively 90 min after beginning the infusion. SAK markedly decreased plasma fibrinogen and alpha 2-antiplasmin levels in dose- and time-dependent manners. These results suggest that this model of thrombosis has a relatively high sensitivity to t-PA, which induced thrombolysis without decreasing fibrinogen and alpha 2-antiplasmin, compared with the other two fibrin-specific thrombolytic agents.
Hirata
Y
Y
Department of Pharmacology, Hamamatsu University School of Medicine, Shizuoka, Japan.
Umemura
K
K
Takiguchi
Y
Y
Uematsu
T
T
Nakashima
M
M
D000818:Animals; D004195:Disease Models, Animal; D005263:Femoral Artery; D005340:Fibrinogen / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D006168:Guinea Pigs; D007262:Infusions, Intravenous; D008297:Male; D008666:Metalloendopeptidases / Q000627:therapeutic use*; D013927:Thrombosis / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use*; D000979:alpha-2-Antiplasmin / Q000378:metabolism
D000979:alpha-2-Antiplasmin; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus