Comparison of Recombinant Plasminogen Activator Inhibitor-1 and Epsilon Amino Caproic Acid in a Hemorrhagic Rabbit Model

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.

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