Thrombus extension was evaluated as previously described in this article. A bolus of rt-PA, 0.4 mg/kg, was injected over 2 min. Heparin, 0.75 mg/kg, and r-hirudin (CGP 39393, Ciba-Geigy), 1.25 mg/kg, were infused over 3 h. Infusion of heparin and r-hirudin started immediately after the rt-PA bolus. The doses of heparin and hirudin were selected according to their ability to double the aPTT. The dose of rt-PA was chosen because it is known to produce 30% thrombolysis, partial lysis being necessary to evaluate fibrin accretion on the thrombus. The accretion of new fibrin on the thrombi was assessed 3 h after the rt-PA bolus, immediately after the end of the heparin or i^hirudin infusion.
The results of the study are shown in Figure 7. Three hours after the rt-PA bolus plus saline infusion, 58 ±7 jxg of radioactive fibrinogen had accreted on the thrombi. Following infusion of heparin and r-hirudin for 3 h after the rt-PA bolus, 51 ± 6 |xg and 21 ± 3 fig of radioactive fibrinogen, respectively, had accreted on the thrombi. The difference between heparin and r-hirudin was statistically significant (p<0.01).
Figure 7. Effects of 3-h infusion of saline, heparin, and hirudin on fibrin accretion on thrombi following bolus injection of rt-PA, 0.4 mg/kg.