Changes in various parameters of fibrinolysis in persons infused with tissue plasminogen activator: special reference to plasminogen activator inhibitor.
Tissue plasminogen activator (t-PA) purified from culture of human lung cells was infused over 30 min at the dose of 7.2 mg or 14.4 mg per person into human male volunteers. T-PA declined rapidly after the cessation of infusion with T1/2, alpha of about 4 min and T1/2, beta of about 40 min. The plasma fibrinogen and plasminogen did not change during and after the infusion of t-PA. The concentration of alpha 2antiplasmin (alpha 2AP) did not change but that of alpha 2AP-plasmin complex increased to about 200 nM at the infusion of 14.4 mg/person. Fragment D was hardly found at the infusion of 7.2 mg but some increase in the concentration of D was observed at the infusion of 14.4 mg. The concentration of free plasminogen activator inhibitor (PAI-1) rapidly declined and kept low up to 150 min, and returned to normal the following day. The concentration of t-PA-PAI-1 complex increased rapidly, and slowly declined after the end of the infusion of t-PA, suggesting no significant release of PAI-1 in response to increase in plasma concentration of t-PA or t-PA-PAI-1 complex. The addition of thrombin to the blood after withdrawal resulted in the significant formation of D-dimer, even at 150 min after the infusion. There was not hyperaggregability of platelets during and after the infusion of t-PA. These results suggest that the infusion of t-PA at the dose of 7.2 mg or 14.4 mg/person for 30 min resulted in high fibrinolytic potential in the blood without the breakdown of fibrinogen or increase in PAI-1.
Takada
A
A
Department of Physiology, Hamatsu University, Sch. Med., Shizuoka, Japan.
Hou
P
P
Mori
T
T
Takada
Y
Y
D000328:Adult; D005342:Fibrinolysis / Q000187:drug effects*; D006023:Glycoproteins / Q000097:blood*; D006400:Hematocrit; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors*; D015849:Plasminogen Inactivators; D010976:Platelet Count / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
D006023:Glycoproteins; D015849:Plasminogen Inactivators; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator