Influence of fibrin and liver blood flow on the turnover and the systemic fibrinogenolytic effects of recombinant human tissue-type plasminogen activator in rabbits.
The influence of the presence of fibrin microclots on the systemic fibrinogenolytic effects of intravenous (IV) recombinant human tissue-type plasminogen activator (rt-PA) was studied by injection of a homogenized fibrin suspension in the femoral vein or artery in rabbits. A linear correlation (P less than .001) was found between the extent of fibrinogen breakdown and the amount of fibrin (0 to 32 mg/kg) injected just prior to the IV infusion of rt-PA at a rate of 10 micrograms/kg/min for 60 minutes. This finding suggests that the systemic activation of the fibrinolytic system observed in some patients during infusion of rt-PA may be due, at least in part, to the presence of fibrin in the vascular bed. The effect of blood flow in the liver on the turnover of rt-PA was measured in rabbits after ligation of the hepatic artery and monitoring of the blood flow in the portal vein with a peristaltic pump. The half-life (t1/2) of rt-PA in plasma was inversely correlated with the logarithm of the rate of the liver blood flow. A doubling of the plasma t1/2 of rt-PA was observed after an eightfold reduction of the liver blood flow, suggesting that delayed clearance of rt-PA may occur in patients with severe cardiovascular failure and impaired liver blood flow.
Bounameaux
H
H
Stassen
J M
JM
Seghers
C
C
Collen
D
D
D000818:Animals; D001810:Blood Volume; D005337:Fibrin / Q000008:administration & dosage / Q000378:metabolism*; D005342:Fibrinolysis; D006207:Half-Life; D006801:Humans; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008099:Liver / Q000098:blood supply*; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology*; D012039:Regional Blood Flow; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D011994:Recombinant Proteins; D005337:Fibrin; D010959:Tissue Plasminogen Activator