PREVENTION OF THROMBOSIS AND RETHROMBOSIS AND ENHANCEMENT OF THE THROMBOLYTIC ACTIONS OF RECOMBINANT TISSUE-TYPE PLASMINOGEN-ACTIVATOR IN THE CANINE HEART BY DMP728, A GLYCOPROTEIN IIB IIIA ANTAGONIST/

1 We studied DMP728, a non-peptide glycoprotein (GP) IIb/IIIa receptor antagonist, for prevention of coronary artery thrombosis or rethrombo sis in a chronic canine model subjected to arterial injury. 2 In proto col I, DMP728 (1.0 mg kg(-1), i.v., n = 8) or saline (n = 8) was admin istered and a 150 mu A anodal current was applied to the intimal surfa ce of the left circumflex coronary artery (LCX). Dogs were monitored f or 6 h and again on each of 5 subsequent days. 3 Ex vivo platelet aggr egation was inhibited but returned to baseline 1 day after drug admini stration. Thrombus weight was reduced (saline, 20.7 +/- 5.0 mg; DMP728 1.7 +/- 0.4 mg; P<0.05), as was infarct size [saline, 27.5 +/- 4.3; D MP728, 1.6 +/- 0.7 (per cent left ventricle); P<0.05]. All control ani mals died by day 3, while all but one of the treated dogs survived the entire protocol (P<0.05). 4 In protocol II, an LCX thrombus was induc ed and thrombolytic therapy was initiated 30 min later. DMP728 (1.0 mg kg(-1), i.v., n = 8) or saline (n = 8) was administered 5 min after r ecombinant tissue-type plasminogen activator infusion had begun. The i ncidence of reocclusion was reduced by DMP728 (saline, 4/8; DMP728, 1/ 8). One day after thrombolysis, 7/8 DMP728-treated animals were alive compared with 1/8 in the control group (P = 0.01). 5 DMP728 inhibited ex vivo platelet aggregation, prevented primary and secondary occlusiv e thrombus formation, reduced thrombus weight and infarct size and inc reased survival in a chronic canine model of coronary artery thrombus formation. DMP728 is an effective anti-platelet intervention when used as the singular adjunctive agent in association with thrombolytic the rapy.