Plasminogen activator inhibitor: a regulator of ancrod-induced fibrin
deposition in rabbits
C Krishnamurti, CF Barr, MA Hassett, GD Young and BM Alving
Plasma levels of a fast-acting plasminogen activator inhibitor (PAI), which
neutralizes both tissue plasminogen activator (t-PA) and urokinase, are
markedly increased in endotoxin-treated rabbits. The ability of this
inhibitor to prevent the fibrinolysis that occurs after a thrombogenic
stimulus was investigated in a rabbit model. Normal and endotoxin-treated
male New Zealand rabbits were infused with ancrod, an enzyme that causes
noncrosslinked fibrin formation in vivo. Ancrod stimulated t-PA activity by
90% in normal rabbits and caused hypofibrinogenemia but did not increase
PAI levels or induce fibrin deposition in target organs. Rabbits injected
with endotoxin (10 micrograms/kg) showed an increase in PAI from less than
1 to 32 U/mL 4 hours later. When ancrod was infused at this time, 90% of
the rabbits developed renal fibrin thrombi. Fibrin deposition was recorded
in 40% of the rabbits that received a lower dose of endotoxin (1.0
microgram/kg) and had a PAI level of 14 U/ml at the time of ancrod infusion
4 hours later. Fibrin deposition did not occur in the endotoxin-treated
rabbits that received normal saline. These data suggest that high levels of
PAI inhibit fibrinolysis in vivo, thereby promoting fibrin clot deposition
following a thrombogenic stimulus.
Volume 69,
Issue 3,
pp. 798-803,
03/01/1987
Copyright © 1987 by The American Society of Hematology
