USE OF A DIRECT THROMBIN INHIBITOR (ARGATROBAN) DURING PULSE-SPRAY THROMBOLYSIS IN EXPERIMENTAL THROMBOSIS

PURPOSE: To evaluate the effectiveness of intravenous and intrathrombi c injection of the thrombin inhibitor argatroban during pulse-spray ph armacomechanical thrombolysis (PSPMT) in experimental venous thrombosi s. MATERIALS AND METHODS: Clots were produced in the inferior vena cav a in 52 rabbits by placement of steel coils and balloon injury to the vessel wall. Two days later, clots were treated with PSPMT. Several tr eatment methods were used: intrathrombic saline, intrathrombic tissue plasminogen activator (t-PA), intrathrombic t-PA with intrathrombic an d intravenous heparin, intrathrombic t-PA with intravenous argatroban, and intrathrombic t-PA with intrathrombic and intravenous argatroban at two different doses. After treatment, the rabbits were killed and r esidual clot was weighed. Pretreatment clot weight was estimated and c lot lysis was assessed. RESULTS: PSPMT with t-PA and adjunctive intrat hrombic heparin resulted in greater lysis than PSPMT with only t-PA (p ercentage of residual clot, 59% +/- 14 vs 81% +/- 28; P = .02). Additi on of intravenous argatroban did not increase lysis, but adjunctive in trathrombic argatroban significantly increased lysis at low doses (37% +/- 16; P = .02) and high doses (34% +/- 6; P = .006) compared with t -PA and intrathrombic heparin. CONCLUSION: In a rabbit model of venous thrombosis, the use of intrathrombic argatroban during PSPMT with t-P A significantly improved clot lysis.