Circulation, Vol 69, 605-610, Copyright © 1984 by American Heart Association
F Van de Werf, SR Bergmann, KA Fox, H de Geest, CF Hoyng, BE Sobel and D Collen
Coronary thrombolysis was induced by intravenous infusion of human
tissue-type plasminogen activator (recombinant human t-PA or rt-PA)
obtained by expression of the cloned gene in a mammalian cell system.
Thrombolysis was detected by the appearance of reperfusion arrhythmia and
confirmed by repeat angiography in anesthetized dogs with 1-hr-old thrombi
of the left anterior descending coronary artery that were induced with a
copper coil. Infusion of 1000 IU (10 micrograms)/kg/min intravenous rt-PA
(n = 9) elicited reperfusion within 13.7 +/- 1.9 min (mean +/- SE) without
producing systemic fibrinolysis or distal coronary embolization. Infusion
of urokinase at the same rate elicited thrombolysis in seven of 10 dogs
within an average of 19.3 +/- 2.2 min. However, distal coronary
embolization occurred in two dogs and systemic fibrinolysis was observed in
all. In three dogs treated with urokinase thrombolysis was obtained only
with subsequent intracoronary infusion. Restoration of myocardial perfusion
and metabolism assessed with positron-emission tomography was consistently
noted in dogs treated with rt-PA. Thus, rt-PA, a clot-selective
thrombolytic agent that does not activate the fibrinolytic system
systemically and that is potentially available in large quantities, in view
of its synthesis by recombinant DNA technology, offers a promising
practical approach for coronary thrombolysis in patients with acute
myocardial infarction.
ARTICLES
Coronary thrombolysis with intravenously administered human tissue-type plasminogen activator produced by recombinant DNA technology
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