A MIMETIC OF THE RGDF-PEPTIDE [ARGININE-GLYCINE-ASPARTIC ACID-PHENYLALANINE] BLOCKS AGGREGATION AND FLOW-INDUCED PLATELET DEPOSITION ON SEVERELY INJURED STENOTIC ARTERIAL-WALL - EFFECTS ON DIFFERENT ANIMAL-MODELS AND IN HUMANS

8-Guanidino-octanoyl-aspartic acid-phenylalanine (SC-49992), a mimetic of the tetrapeptide arginine-glycine aspartic acid-phelylalanine, inh ibits fibrinogen and vitronectin binding to GP IIb/IIIa. SC-49992 effe cts on impedance and optical aggregation were compared in different sp ecies (human, porcine and dog). SC-49992 induced significant inhibitio n both in whole blood and PRP aggregation, in all species; however, po rcine platelets had a SC-49992 IC50 = 2.5mM while human and dog platel ets had a significant lower IC50 (1 mu M and 1.5 mu M, respectively). Inhibition of flow-mediated platelet deposition on severely injured ve ssels was studied in porcine blood at high and low shear rates for 5 m inutes. Additionally, studies were performed in vessels with 80% steno sis. SC-49992 reduced platelet deposition both at high and low shear r ate in parallel streamlined flow and in stenotic conditions. The lower affinity of porcine platelets for SC-49992 seems to be due to a speci es difference at the GPIIb/IIIa receptor RGD-sequence level.