Sustained thrombolysis with DNA-recombinant tissue type plasminogen
activator in rabbits
G Agnelli, MR Buchanan, F Fernandez, J Van Ryn and J Hirsh
Tissue type plasminogen activator (t-PA) is an effective thrombolytic agent
in experimental animals. The duration of the thrombolytic effect of infused
t-PA is unknown. We compared the duration of the thrombolytic effect of
t-PA with streptokinase by measuring the lysis of 125I-fibrin-labeled
thrombi in rabbit jugular veins at different times after a bolus injection
of the fibrinolytic agents. The pharmacodynamics of both thrombolytic
agents were determined in rabbits using a sensitive ex vivo fibrinolytic
assay. Streptokinase and t-PA were given as a bolus dose of 15,000 U/kg.
There was no detectable circulating fibrinolytic activity 30 minutes after
the bolus dose of t- PA and 120 minutes after the bolus dose of
streptokinase. The t-PA injection produced 34% thrombolysis at 30 minutes,
90% thrombolysis at 120 minutes, and 96% thrombolysis at 240 minutes. The
streptokinase injection produced 17% thrombolysis at 30 minutes, 34% at 120
minutes, and 34% at 240 minutes. These observations indicate that the
thrombolytic effect of t-PA is sustained beyond its time of clearance from
the circulation whereas the thrombolytic effect of streptokinase closely
parallels its activity in the circulation.
Volume 66,
Issue 2,
pp. 399-401,
08/01/1985
Copyright © 1985 by The American Society of Hematology
