Comparison of recombinant plasminogen activator inhibitor-1 and epsilon amino caproic acid in a hemorrhagic rabbit model.
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 micrograms 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.
Racanelli
A L
AL
Du Pont Merck Pharmaceutical Company, Cardiovascular Sciences, Wilmington, DE 19880-0400.
Diemer
M J
MJ
Dobies
A C
AC
Dubin
J R
JR
Reilly
T M
TM
D000595:Amino Acid Sequence; D015119:Aminocaproic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008969:Molecular Sequence Data; D015849:Plasminogen Inactivators / Q000494:pharmacology* / Q000627:therapeutic use; D011817:Rabbits; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors*
D015849:Plasminogen Inactivators; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D015119:Aminocaproic Acid