ASPIRIN DOES NOT POTENTIATE EFFECT OF SUBOPTIMAL DOSE OF THE THROMBININHIBITOR INOGATRAN DURING CORONARY THROMBOLYSIS

Objectives: Coronary artery often reoccludes after thrombolytic therap y with recombinant tissue-plasminogen activator (rt-PA). This reocclus ion is thought to be due to in situ platelet activation mediated by th romboxane (Tx) A(2) and thrombin; hence, aspirin and thrombin inhibito rs are often used in patients with acute myocardial infarction. This s tudy was designed to examine the modulation of coronary artery reocclu sion by a novel low molecular weight direct thrombin inhibitor inogatr an with or without aspirin. Methods: 22 dogs with electrically-induced occlusive intracoronary thrombus were treated with saline (n = 7, gro up A), or high dose inogatran (0.25 mg/kg bolus followed by 0.6 mg/kg per h for 2 h, n = 5, group B), or low dose inogatran (0.125 mg/kg bol us followed by 0.3 mg/kg per h for 2 h, n = 5, group C), or aspirin low dose inogatran (n = 5, Group D). Recombinant tissue-plasminogen ac tivator (rt-PA) was infused for 20 min starting 2 min after the bolus in all dogs. Coronary artery blood flow was monitored for 120 min afte r rt-PA administration. Results: Reperfusion rates were similar in all groups, but the time to reperfusion was shortest in group B dogs (18 +/- 2 min vs. 32 +/- 7 min in group A dogs, P < 0.05). Reocclusion rat es were 80%, 0%, 50%, and 60% in groups A, B, C, and D dogs, respectiv ely. The restored blood flow persisted for 19 +/- 10, > 120 min, 71 +/ - 30 and 54 +/- 26 min in groups A, B, C, and D dogs, respectively. At the end of rt-PA infusion, prothrombin time (PT) and activated partia l thromboplastin time (APTT) were increased 1.3-2 times the control va lue, and the changes in PT and APTT were similar in all groups. Thromb in generation and activity, assessed by rise in thrombin-antithrombin complex and fibrinopeptide A levels, and decrease in fibrinogen levels were most marked in group A dogs, and less so in group B, C and D dog s. Conclusions: These data show that high dose of direct thrombin inhi bitor inogatran shortens time to reflow and abolishes coronary artery reocclusion. However, aspirin does not potentiate the effect of subopt imal doses of inogatran.