Circulation, Vol 82, 1476-1484, Copyright © 1990 by American Heart Association
M Heras, JH Chesebro, MW Webster, JS Mruk, DE Grill, WJ Penny, EJ Bowie, L Badimon and V Fuster
Three dosages (0.3, 0.7, and 1.0 mg/kg) of recombinant hirudin, a specific
inhibitor of thrombin, were compared with heparin (50 units/kg) and placebo
for reducing thrombus formation in the carotid arteries of 50 pigs after
deep injury by balloon dilatation. Each drug was administered as a bolus
followed immediately by a continuous infusion of the same dose per hour.
Major end points were quantitative indium-111-labeled platelet and
iodine-125-labeled fibrinogen deposition and the incidence of mural
thrombosis. This study showed that heparin, at a dose that prolonged the
activated partial thromboplastin time (APTT) to twice the control time, did
not prevent mural thrombosis or significantly reduce platelet deposition
compared with placebo but did reduce fibrinogen deposition. Recombinant
hirudin markedly reduced platelet and fibrinogen deposition in a
dose-related manner and totally eliminated mural thrombosis at an APTT of
two to three times that of control. Platelet deposition (x 10(6)/cm2, mean
+/- SEM) in areas of deep arterial injury for the placebo, heparin, and
0.3, 0.7, and 1.0 mg/kg hirudin groups was 54 +/- 21, 33 +/- 9, 22 +/- 6, 8
+/- 1, and 7 +/- 1, respectively; electron microscopy showed a single layer
(or less) of platelets at the two highest hirudin dosages. The incidence of
macroscopic mural thrombosis was 76% with placebo, 57% with heparin, 46%
with 0.3 mg/kg hirudin; there were no thrombi with 0.7 or 1.0 mg/kg hirudin
(p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Hirudin, heparin, and placebo during deep arterial injury in the pig. The in vivo role of thrombin in platelet-mediated thrombosis
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905.
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