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Thrombolytic properties of Desmodus rotundus (vampire bat) salivary
plasminogen activator in experimental pulmonary embolism in rats
W Witt, B Baldus, P Bringmann, L Cashion, P Donner and WD Schleuning
Laboratory for Thrombosis Research, Schering AG, Berlin, Germany.
rDSPA alpha 1 (recombinant Desmodus salivary plasminogen activator alpha 1)
is a recombinant protein corresponding to a natural plasminogen activator
from the vampire bat Desmodus rotundus. The thrombolytic properties of
rDSPA alpha 1 and tissue-type plasminogen activator (t-PA) were compared in
a rat model of pulmonary embolism. Whole blood clots, produced in vitro and
labeled with 125I-fibrinogen, were embolized into the lungs of anesthetized
rats. Thrombolysis was calculated from the difference between initial clot
radioactivity and that remaining in the lungs at 60 minutes. Blood was
sampled for gamma counting, measurement of hemostatic factors, and
plasminogen activator antigen levels. Thrombolysis at 3, 10, 30, and 100
nmol/kg intravenously (10% bolus, 90% over 60 minutes) amounted to 30% +/-
2%, 51% +/- 4%, 85% +/- 4%, 98% +/- 0% for rDSPA alpha 1 and 30% +/- 3%,
41% +/- 3%, 57% +/- 6%, 93% +/- 2% for t-PA (controls: 29% +/- 2%; mean +/-
SEM, n greater than or equal to 6). t-PA at 100 nmol/kg significantly
decreased fibrinogen, plasminogen, and alpha 2- antiplasmin levels by 33%
+/- 7%, 38% +/- 8%, and 61% +/- 9%, whereas rDSPA alpha 1 at 100 nmol/kg
only lowered alpha 2-antiplasmin significantly (by 29% +/- 6%). Compared
with t-PA, rDSPA alpha 1 is the more potent and more clot selective (fibrin
specific) thrombolytic agent. These results suggest that rDSPA alpha 1 may
be safer and more efficacious than currently used thrombolytics.
Volume 79,
Issue 5,
pp. 1213-1217,
03/01/1992
Copyright © 1992 by The American Society of Hematology
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