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

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 segment 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 persisting 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 observation period in all of 10 dogs and for 24 hours in 4 of the 10 dogs. 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) injection, 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 graft patency at 2, 24, 48, and 72 hours after study drug injection were 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 (approximately 20%; P=.01 versus baseline) within 24 hours and complete recovery (P=not significant versus baseline) within 48 hours. Pathological examination of patent everted grafts revealed significant residual mural thrombus in all groups. Thus, 7E3-F(ab')(2) reduced platelet-rich arterial eversion graft thrombosis, and this effect persisted beyond normalization of bleeding time prolongation and inhibition of ex vivo platelet aggregation. Mural thrombus deposition still occurred with 7E3-F(ab')(2), but vascular occlusion was markedly reduced.