FAILURE OF THROMBIN INHIBITION TO PREVENT INTRACORONARY THROMBOSIS INTHE DOG

1. Recurrent occlusion after thrombolysis may be caused by thrombin re ceptor-mediated platelet thrombosis occurring in a residual stenosis, To test the relative importance of the platelet thrombin receptor unde r conditions of high shear and endothelial damage (the Felts model of intracoronary thrombosis) we used the specific thrombin inhibitor reco mbinant hirudin, 2. A critical coronary artery stenosis overlying an a rea of crushed endothelium was used in a repeated measures study of ei ght open-chest anaesthetized dogs. In the control period, recurrent th rombosis occurred at an average rate (+/- SD) of 4.4 +/- 1.4 ml/min(2) . Infusion of recombinant hirudin at 1.6 mg h(-1) kg(-1) abolished rec urrent thrombosis in three dogs, but the thrombosis rate averaged 4.7 +/- 2.9 ml/min(2) in the remaining five animals. 3. Haematological mea surements demonstrated the activity of recombinant hirudin: thrombin t ime rose from 13 +/- 3s to > 165s universally (P < 0.01), partial thro mboplastin time rose from 14 +/- 2s to 29 +/- 10s (P < 0.01), Bleeding time rose from 2.3 +/- 0.8 min to 4.7 +/- 1.8 min (P < 0.05), 4. It i s concluded that specific thrombin inhibition, despite affecting coagu lation, is relatively ineffective in preventing intracoronary thrombos is under conditions of high shear.