Objective: To compare the thrombolytic effects of the two dosing regimes with urokinase (UK) in a canine model of pulmonary thromboembolism induced by radioactive blood clots.
Methods: Seventeen dogs were randomly assigned into three groups: the control group, the UK(2h) group (UK infused over 2 hours) and the UK(12h) group (UK given over 12 hours). The thrombolytic differences was investigated among the three groups. Thrombolysis was assessed by continuously counting over both lung fields with single photon emission computed tomography (SPECT) and calculated by regions of interest (ROI) technology and by counting radioactivity in the lung in vitro. The extent of thrombolysis was calculated as the difference between the radioactivity originally incorporated in the clot (decay-corrected) and the radioactivity in the lung in vitro.
Results: In three groups, the lysis rates measured by ROI technology were (6.2 +/- 4.0)%, (39.5 +/- 13.9)%, and (16.9 +/- 8.9)% respectively, and (6.0 +/- 2.7)%, (42.8 +/- 12.4)%, and (17.7 +/- 9.3)% by the method in vivo. The thrombolytic ratio of the UK(2h) group was significantly higher than that of the other two groups (P < 0.01), and there was no marked difference between the control group and the UK(12h) group. There was a thrombolytic peak in the UK(2h) group at the first four hours after infusion of agent.
Conclusions: For the fresh thrombi, the UK(2h) regime is superior to the UK(12h) due to its higher thrombolytic ratio and prompt thrombolytic property. The model and methods are highly reliable.