Reocclusion after thrombolysis: a problem solved by hirudin?
The effect of recombinant hirudin (r-hir), unfractionated heparin (UFH) and acetylsalicylic acid (ASA) on the incidence of reocclusion after thrombolysis with plasminogen activator (rt-PA) was evaluated in anaesthetized rabbits. Formation of a platelet rich thrombus was achieved by implantation of a copper coil into the iliac artery. The occluded artery was recanalized in six of ten animals by intravenous administration of rt-PA given as a bolus injection of 0.1 mg/kg followed by infusion of 0.5 mg/kg/h. Within 1 h after termination of rt-PA infusion rethrombosis was observed in 100% of recanalized vessels. The incidence of reocclusion was diminished by r-hir in a dose-dependent manner to 50% after infusion of 0.05 mg/kg/h and to 25% after 0.1 mg/kg/h. No effect on APTT was detectable in this dosage after 3 h infusion. UFH in a dosage increasing APTT two-fold (35 U/kg/h) did not reduce the reocclusion rate. 100 U/kg/h UFH increased APTT to greater than 3 min and reduced reocclusion rates to 50%. ASA showed a minor effect on the incidence of restenosis whereas the combination of 0.1 mg/kg/h r-hir plus bolus injection of 10 mg/kg ASA led to a further reduction in reocclusion rates to only 11% and an increase in reperfusion rates from 60 to 90%. Our experiments indicate that the combination of plasminogen activator with r-hir may be a useful approach for the prophylaxis of early reocclusion.
Rübsamen
K
K
Knoll AG, Department of Angiology, Ludwigshafen, Germany.
Eschenfelder
V
V
D000818:Animals; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use; D024764:Hirudin Therapy; D006629:Hirudins / Q000031:analogs & derivatives* / Q000494:pharmacology; D007083:Iliac Artery; D010314:Partial Thromboplastin Time; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012008:Recurrence; D015424:Reperfusion; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D006629:Hirudins; D011994:Recombinant Proteins; C072488:LU 52369; D006493:Heparin; D010959:Tissue Plasminogen Activator; D001241:Aspirin