The role of type-1 plasminogen activator inhibitor in failure of thrombolytic therapy with recombinant tissue plasminogen activator.
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)
Huber
K
K
2nd Department of Internal Medicine, University of Vienna, Austria.
Beckmann
R
R
Rauscha
F
F
Probst
P
P
Kaindl
F
F
Binder
B R
BR
D000368:Aged; D003326:Coronary Circulation / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012008:Recurrence; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000097:blood
D017395:Plasminogen Activator Inhibitor 1; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator