|
|||||||||
|
|
|
|
|
|
|
|
|
|
|
C Krishnamurti, C Bolan, CA Colleton, TM Reilly and BM Alving
Department of Hematology, Walter Reed Army Institute of Research,
Washington, DC 20307-5100.
The role of defective fibrinolysis caused by elevated activity of
plasminogen activator inhibitor-1 (PAI-1) in promoting fibrin deposition in
vivo has not been well established. The present study compared the efficacy
of thrombin or ancrod, a venom-derived enzyme that clots fibrinogen, to
induce fibrin formation in rabbits with elevated PAI-1 levels. One set of
male New Zealand rabbits received intravenous endotoxin to increase
endogenous PAI-1 activity followed by a 1-hour infusion of ancrod or
thrombin; another set of normal rabbits received intravenous human
recombinant PAI-1 (rPAI-1) during an infusion of ancrod or thrombin. Thirty
minutes after the end of the infusion, renal fibrin deposition was assessed
by histopathology. Animals receiving endotoxin, rPAI-1, ancrod, or thrombin
alone did not develop renal thrombi. All endotoxin-treated rabbits
developed fibrin deposition when infused with ancrod (n = 4) or thrombin (n
= 6). Fibrin deposition occurred in 7 of 7 rabbits receiving both rPAI-1
and ancrod and in only 1 of 6 receiving rPAI-1 and thrombin (P < .01).
In vitro, thrombin but not ancrod was inactivated by normal rabbit plasma
and by purified antithrombin III or thrombomodulin. The data indicate that
elevated levels of PAI-1 promote fibrin deposition in rabbits infused with
ancrod but not with thrombin. In endotoxin-treated rabbits, fibrin
deposition that occurs with thrombin infusion may be caused by decreased
inhibition of procoagulant activity and not increased PAI-1 activity.
This article has been cited by other articles:
| ||||||||||
 |
 |
 |
|||||||
 |
 |
 |
 |
 |
 |
 |
 |
||
| Copyright © 1993 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
