Coronary thrombolysis with Desmodus salivary plasminogen activator in dogs. Fast and persistent recanalization by intravenous bolus administration.
BACKGROUND
DSPA (Desmodus salivary plasminogen activator) is a new thrombolytic agent corresponding to a natural plasminogen activator discovered in the saliva of the vampire bat Desmodus rotundus. Compared with tissue plasminogen activator (TPA), DSPA, produced in a recombinant cell line, is more fibrin cofactor dependent than TPA.


RESULTS
The thrombolytic properties of DSPA and TPA were compared in a canine model of copper coil-induced 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 micrograms/kg resulted in a 100% incidence (6 of 6) of recanalization within 37, 23, and 18 minutes, respectively. TPA at 63 and 125 micrograms/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 micrograms/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 alpha 2-antiplasmin decreased significantly only with 125 micrograms/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.


CONCLUSIONS
In 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 half-life of DSPA may allow for single bolus administration in the treatment of acute myocardial infarction.
Witt
W
W
Department of Cardiovascular Pharmacology, Research Laboratories of Schering AG, Berlin, Germany.
Maass
B
B
Baldus
B
B
Hildebrand
M
M
Donner
P
P
Schleuning
W D
WD
D000818:Animals; D003328:Coronary Thrombosis / Q000097:blood / Q000628:therapy*; D004285:Dogs; D006487:Hemostasis / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D010960:Plasminogen Activators / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000493:pharmacokinetics / Q000627:therapeutic use
C069588:salivary plasminogen activator alpha 1, Desmodus rotundus; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator