title: Thrombosis triggered by severe arterial lesions is inhibited by oral administration of a glycoprotein IIb/IIIa antagonist.
abstract: Platelet aggregation and thrombosis play an important role in the onset of acute coronary events. Regardless of the stimulus for activation, platelet thrombus formation is ultimately regulated through the IIb/IIIa receptor complex. The effects of oral administration of xemilofiban, a non-peptide mimetic of the RGDF sequence of the IIb/IIIa receptor complex, on thrombus formation were evaluated in a canine model. Xemilofiban significantly reduced platelet deposition on severely damaged arterial wall. Platelet deposition was reduced at both low (13 +/- 1 from 56 +/- 18 x 10(6) platelets cm-2; P < 0.05) and high (23 +/- 2 from 111 +/- 21 x 10(6) platelets cm-2; P < 0.01) shear rates. Platelet deposition was reduced to a monolayer as seen by electron microscopy (platelet-vessel wall interaction). Therefore, the availability of an orally active IIb/IIIa antagonist for chronic use may have significant value in preventing thrombus formation in those clinical situations associated with severe arterial injury, such as atherosclerotic plaque disruption.
authors.affiliation: Cardiovascular Biology Research Laboratories, Mount Sinai School of Medicine, NY 10029, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Badimon
authors.forename: B
authors.initials: B
authors.lastname: Meyer
authors.forename: L P
authors.initials: LP
authors.lastname: Feigen
authors.forename: D A
authors.initials: DA
authors.lastname: Baron
authors.forename: J H
authors.initials: JH
authors.lastname: Chesebro
authors.forename: V
authors.initials: V
authors.lastname: Fuster
authors.forename: L
authors.initials: L
authors.lastname: Badimon
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001550:Benzamidines; D001783:Blood Flow Velocity / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects* / Q000648:ultrastructure; D020212:Carotid Artery Injuries; D004285:Dogs; D008855:Microscopy, Electron, Scanning; D010477:Perfusion; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*
chemical_list: D001550:Benzamidines; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C091295:xemilofiban