Coronary Thrombolysis WithDesmodusSalivary Plasminogen Activator in DogsFast and Persistent Recanalization by Intravenous Bolus Administration
作者:
Werner Witt,
Bernhard Maass,
Berthold Baldus,
Michael Hildebrand,
Peter Donner,
Wolf-Dieter Schleuning,
期刊:
Circulation
(OVID Available online 1994)
卷期:
Volume 90,
issue 1
页码: 421-426
ISSN:0009-7322
年代: 1994
出版商: OVID
关键词: reocclusion;tissue plasminogen activator;thrombolysis;Desmodussalivary plasminogen activator
数据来源: OVID
摘要:
DSPA (Desmodussalivary plasminogen activator) is a new thrombolytic agent corresponding to a natural plasminogen activator discovered in the saliva of the vampire batDesmodus rotundus. Compared with tissue plasminogen activator (TPA), DSPA, produced in a recombinant cell line, is more fibrin cofactor dependent than TPA.Methods and ResultsThe thrombolytic properties of DSPA and TPA were compared in a canine model of copper coilinduced coronary thrombosis. All dogs received heparin 200 IU/kg IV and SC. Whereas controls did not reperfuse within 180 minutes (none of six), intravenous bolus administration of DSPA at 25, 50, and 100 μg/kg resulted in a 100% incidence (6 of 6) of recanalization within 37, 23, and 18 minutes, respectively. TPA at 63 and 125 mu;g/kg reopened the coronaries in 33% (two of six) and 50% (three of six) of cases within 40 minutes. Eighty-three percent (5 of 6) of the arteries were still patent 3 hours after 50 and 100 mu;/kg DSPA, whereas only 20% (one of five) of all coronaries originally recanalized with both doses of TPA were still open at 3 hours. Plasma levels of α2-antiplasmin decreased significantly only with 125 mu;g/kg TPA. The clearance of DSPA (2.3 to 3.5 mL · min−1· kg−1) was lower compared with TPA (11.4 to 20 mL · min−1· kg−1) due to a prolonged terminal half- life.ConclusionsIn a canine coronary thrombosis model, DSPA exhibited higher potency and recanalized coronary arteries faster and with a lower incidence of reocclusion than TPA. Its properties may translate into a higher efficacy in patients compared with available thrombolytic agents. The long halflife of DSPA may allow for single bolus administration in the treatment of acute myocardial infarction.
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