arginyl-glycyl-aspartyl-phenylalanine and Disease-Models--Animal

8-Guanidino-octanoyl-aspartic acid-phenylalanine (SC-49992), a mimetic of the tetrapeptide arginine-glycine-aspartic acid-phenylalanine, is a potent inhibitor of platelet aggregation. In this study, the authors examined the effects of SC-49992 on the time to lysis of thrombi and the time to reocclusion in the canine coronary artery, which had been treated with tissue plasminogen activator. A lysis/reocclusion model was used that was originally designed so that the reoccluding thrombus was platelet rich. SC-49992 decreased the time to lysis in response to recombinant tissue plasminogen activator in a dose-dependent manner. The reduction of the lytic time was significant at the highest dose of 0.08 mg kg-1 min-1 (from 22.8 +/- 8.2 to 7.4 +/- 1.4 min, P < .05). The reocclusion time was prolonged at all doses of SC-49992 (from a control level of 3.4 +/- 0.6 min to more than 50 min at all doses of SC-49992, P < .05). At the 0.06- and 0.08-mg kg-1 min-1 doses, all but one animal in each group did not have a reocclusion during the time of the experiment. In those animals that did have reocclusions in the presence of SC-4992, ex vivo platelet aggregation was inhibited 100% at the time of reocclusion. The bleeding times were prolonged in these animals at the levels of inhibition in which the compound was the most effective.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amino Acid Sequence; Animals; Antibodies; Bleeding Time; Coronary Thrombosis; Dipeptides; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Drug Synergism; Female; Half-Life; Male; Molecular Sequence Data; Oligopeptides; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Membrane Glycoproteins; Recombinant Proteins; Thrombolytic Therapy; Tissue Plasminogen Activator