Failure of thrombin inhibition to prevent intracoronary thrombosis in the dog.
1. Recurrent occlusion after thrombolysis may be caused by thrombin receptor-mediated platelet thrombosis occurring in a residual stenosis. To test the relative importance of the platelet thrombin receptor under conditions of high shear and endothelial damage (the Folts model of intracoronary thrombosis) we used the specific thrombin inhibitor recombinant hirudin. 2. A critical coronary artery stenosis overlying an area of crushed endothelium was used in a repeated measures study of eight open-chest anaesthetized dogs. In the control period, recurrent thrombosis occurred at an average rate (+/- SD) of 4.4 +/- 1.4 ml/min2. Infusion of recombinant hirudin at 1.6 mg h-1 kg-1 abolished recurrent thrombosis in three dogs, but the thrombosis rate averaged 4.7 +/- 2.9 ml/min2 in the remaining five animals. 3. Haematological measurements demonstrated the activity of recombinant hirudin: thrombin time rose from 13 +/- 3 s to > 165 s universally (P < 0.01), partial thromboplastin time rose from 14 +/- 2 s to 29 +/- 10 s (P < 0.01). Bleeding time rose from 2.3 +/- 0.8 min to 4.7 +/- 1.8 min (P < 0.05). 4. It is concluded that specific thrombin inhibition, despite affecting coagulation, is relatively ineffective in preventing intracoronary thrombosis under conditions of high shear.
Belcher
P R
PR
University Department of Cardiac Surgery, Royal Infirmary, Glasgow, U.K.
Drake-Holland
A J
AJ
Hynd
J W
JW
Noble
M I
MI
D000818:Animals; D000991:Antithrombins / Q000627:therapeutic use*; D001760:Bleeding Time; D003328:Coronary Thrombosis / Q000097:blood / Q000517:prevention & control*; D004285:Dogs; D024764:Hirudin Therapy; D010314:Partial Thromboplastin Time; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013918:Thrombin Time; D017211:Treatment Failure
D000991:Antithrombins; D011994:Recombinant Proteins; D013917:Thrombin