Summary
A rabbit ear model of blood loss was developed to compare the effects of an active
form of recombinant plasminogen activator inhibitor-1 (rPAI-1) with epsilon amino
caproic acid (EACA) in antagonizing tissue-type plasminogen activator (r-tPA)-induced
blood loss. The antagonism of both rebleeding, which occurs as a result of hemostatic
plug degradation, and r-tPA-induced hemorrhage, where rabbits lose approximately 30%
of their blood volume, was studied. rPAI-1 (1 mg/kg i. v.) or EACA (70 mg/kg i. v.)
antagonized the rebleeding induced by r-tPA (10 μg kg-1 min-1) to a similar extent. In the hemorrhagic studies, rPAI-1 effectively antagonized
the r-tPA-induced hemorrhage with an ED50 of 3 mg/kg i. v., while the ED50 obtained for EACA was 230 mg/kg i. v. rPAI-1 may be of value in reversing r-tPA-induced
blood loss during thrombolytic therapy or in clinical situations where excessive fibrinolysis
contributes to bleeding.
