TIME-COURSE OF THE EFFECTS OF A SINGLE BOLUS INJECTION OF F(AB')(2) FRAGMENTS OF THE ANTIPLATELET GPIIB IIIA ANTIBODY 7E3 ON ARTERIAL EVERSION GRAFT OCCLUSION, PLATELET-AGGREGATION, AND BLEEDING-TIME IN DOGS/
Rg. Kiss et al., TIME-COURSE OF THE EFFECTS OF A SINGLE BOLUS INJECTION OF F(AB')(2) FRAGMENTS OF THE ANTIPLATELET GPIIB IIIA ANTIBODY 7E3 ON ARTERIAL EVERSION GRAFT OCCLUSION, PLATELET-AGGREGATION, AND BLEEDING-TIME IN DOGS/, Arteriosclerosis and thrombosis, 14(3), 1994, pp. 367-374
The time course of the effects of a single intravenous bolus injection
of 10 mg/kg aspirin or 0.8 mg/kg F(ab'), fragments of the monoclonal
antiplatelet glycoprotein IIb/IIIa receptor antibody 7E3 [7E3-F(ab')(2
)] on arterial occlusion, platelet aggregation, and bleeding time was
studied in 30 dogs with an everted (inside out) carotid arterial segme
nt inserted into the femoral artery. In the absence of an antiplatelet
agent, the eversion grafts occluded spontaneously with platelet-rich
thrombus within 30 minutes. With aspirin, arterial occlusion persistin
g for 2 hours occurred in 5 of 10 dogs and cyclic occlusion and reflow
in 4 animals; arterial occlusion was observed in all dogs at 24 hours
. With 7E3-F(ab')(2), arterial patency persisted throughout a 2-hour o
bservation period in all of 10 dogs and for 24 hours in 4 of the 10 do
gs. Contralateral eversion grafting 24 hours after aspirin or 7E3-F(ab
')(2) injection was associated with graft patency for 2 hours in 1 of
5 aspirin dogs and in 3 of 5 7E3-F(ab')(2) dogs; patency persisted for
24 hours. In dogs grafted 48 hours; after aspirin or 7E3-F(ab')(2) in
jection, patency at 24 hours was seen in 0 of 5 dogs given aspirin and
3 of 5 dogs given 7E3-F(ab')(2) The overall frequencies of arterial g
raft patency at 2, 24, 48, and 72 hours after study drug injection wer
e significantly higher in the 7E3-F(ab')(2) groups than in the aspirin
groups (P<.0005, n=10 in each group; P<.05, n=15; P<.005, n=15; and P
=.05, n=5, respectively). ADP-induced ex vivo platelet aggregation was
abolished after 7E3-F(ab')(2) injection with partial recovery (approx
imately 20%; P=.01 versus baseline) within 24 hours and complete recov
ery (P=not significant versus baseline) within 48 hours. Pathological
examination of patent everted grafts revealed significant residual mur
al thrombus in all groups. Thus, 7E3-F(ab')(2) reduced platelet-rich a
rterial eversion graft thrombosis, and this effect persisted beyond no
rmalization of bleeding time prolongation and inhibition of ex vivo pl
atelet aggregation. Mural thrombus deposition still occurred with 7E3-
F(ab')(2), but vascular occlusion was markedly reduced.