Circulation, Vol 80, 1775-1782, Copyright © 1989 by American Heart Association
EJ Haskel, SP Adams, LP Feigen, JE Saffitz, RJ Gorczynski, BE Sobel and DR Abendschein
The composition of an evolving arterial thrombus may be a determinant of
how effectively pharmacologic agents prevent reocclusion after initially
successful thrombolysis. In this study, reoccluding platelet- or
fibrin-rich thrombi as delineated by scanning electron microscopy were
produced selectively in the femoral arteries of dogs with the use of
electrically induced vascular injury or implantation of copper wire,
respectively. Initial thrombolysis after intravenous infusion of tissue-
type plasminogen activator (1 mg/kg over 30 minutes) was less frequent in
the preparation producing platelet-rich thrombi than in that producing
fibrin-rich thrombi (lysis in 19 of 24 versus 18 of 18, p = 0.06). In dogs
with initial arterial recanalization, intravenous infusion of
arginine-glycine-aspartate-O-methyltyrosine amide (RGDY), which competes
with fibrinogen for binding to platelet glycoprotein IIb/IIIa receptors,
prevented reocclusion caused by recurrence of platelet-rich thrombi in six
of six dogs within 90 minutes; reocclusion occurred in five of seven
saline-infused control dogs (p = 0.02). RGDY was only partially effective
in preventing reocclusion caused by recurrence of fibrin-rich thrombi
(reocclusion in three of six versus five of six controls, p = 0.54).
Similar results were obtained with aspirin in both preparations. At least
98% of platelet aggregation induced ex vivo by collagen was inhibited by
either RGDY or aspirin. In contrast with aspirin, however, platelet
function returned to normal within 1 hour after discontinuation of RGDY.
Thus, the relative proportions of platelets or fibrin incorporated into
thrombi influence the efficacy of both tissue-type plasminogen activator
for inducing thrombolysis and antiplatelet agents for preventing
reocclusion. RGDY is a potent, short-acting inhibitor of platelet
aggregation that effectively prevents reocclusion under conditions in which
platelet deposition predominates.
ARTICLES
Prevention of reoccluding platelet-rich thrombi in canine femoral arteries with a novel peptide antagonist of platelet glycoprotein IIb/IIIa receptors
Cardiovascular Division, Washington University School of Medicine, St. Louis, MO 63110.
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