The role of type-1 plasminogen activator inhibitor in failure of thrombolytic therapy with recombinant tissue plasminogen activator. 1993

K Huber, and R Beckmann, and F Rauscha, and P Probst, and F Kaindl, and B R Binder
2nd Department of Internal Medicine, University of Vienna, Austria.

We investigated the possible role of type-1 plasminogen activator inhibitor (PAI-1) on success or failure of thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) in 10 responders and 10 non-responders with acute myocardial infarction and early initiation of therapy within 2 h of onset using the common infusion scheme (100 mg rt-PA over 3 h). We determined plasma levels of t-PA (activity and antigen) as well as PAI-1 (activity and antigen) in samples obtained before, during and after thrombolytic treatment and compared the course of each of those parameters between responders and non-responders to therapy. Success or failure of treatment was determined by a combination of noninvasive methods and proven by coronary angiography within 5 days of initiation of thrombolysis. Thirty, 60, 90, and 120 min after initiation of rt-PA infusion, specific t-PA activities in plasma of responders were 0.62, 0.63, 0.62, and 0.57 (IU/ng/ml), respectively, as compared to 0.42, 0.42, 0.40, and 0.32 (IU/ng/ml) in nonresponders (p < 0.001). Between 4 and 8 h after initiation of therapy, a time span known to be critical for thrombotic reocclusion, specific activities were still significantly elevated in responders as compared to non-responders (p < 0.01). PAI-1 activity levels, which were not detectable during rt-PA infusion in either group, recovered to pre-treatment values 2 h earlier in non-responders.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009203 Myocardial Infarction NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION). Cardiovascular Stroke,Heart Attack,Myocardial Infarct,Cardiovascular Strokes,Heart Attacks,Infarct, Myocardial,Infarction, Myocardial,Infarctions, Myocardial,Infarcts, Myocardial,Myocardial Infarctions,Myocardial Infarcts,Stroke, Cardiovascular,Strokes, Cardiovascular
D010959 Tissue Plasminogen Activator A proteolytic enzyme in the serine protease family found in many tissues which converts PLASMINOGEN to FIBRINOLYSIN. It has fibrin-binding activity and is immunologically different from UROKINASE-TYPE PLASMINOGEN ACTIVATOR. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. Alteplase,Plasminogen Activator, Tissue-Type,T-Plasminogen Activator,Tissue-Type Plasminogen Activator,Actilyse,Activase,Lysatec rt-PA,TTPA,Tisokinase,Tissue Activator D-44,Lysatec rt PA,Lysatec rtPA,Plasminogen Activator, Tissue,Plasminogen Activator, Tissue Type,T Plasminogen Activator,Tissue Activator D 44,Tissue Type Plasminogen Activator
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D012008 Recurrence The return of a sign, symptom, or disease after a remission. Recrudescence,Relapse,Recrudescences,Recurrences,Relapses
D003326 Coronary Circulation The circulation of blood through the CORONARY VESSELS of the HEART. Circulation, Coronary
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D005260 Female Females
D005342 Fibrinolysis The natural enzymatic dissolution of FIBRIN. Fibrinolyses

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