Objective To determine the effect of the combined use of urokinase and glycoprotein IIb/IIIa-targeted microbubbles prepared by direct conjugation method to dissolve the thromb.
Methods Urokinase and RGDS were in conjunction with microbubbles (SonoVue) by the direct conjugation method. The size, shape, fluorescent intensity, the binding rates of Urokinase and RGDS, and the activity of Urokinase were measured and analysed. A total of 42 rabbits with platelet-rich thrombi in the femoral artery were randomised into seven treatment groups (n=6): 1) ultrasound alone (US); 2) ultrasound plus non-targeted microbubbles (US+M); 3) urokinase alone (UK); 4) ultrasound, non-targeted microbubble and urokinase (US+M+UK); 5) ultrasound plus RGDS microbubble (US+R); 6) RGDS microbubble plus urokinase (R+UK); and 7) ultrasound, RGDS microbubble and urokinase (US+R+UK). US in diagnostic ultrasound were simultaneously applied over the thrombus up to 30 min. The thrombolytic effect was evaluated at 120 min post treatment.
Results SonoVue, Urokinase and RGDS were combined successfully. In vitro thrombolysis experiment indicated that the urokinase in the prepared contrast agent had activity (p<0.01). For US, UK, US+M, US+R and US+M+UK groups, recanalisation was failed with the blood flow less than 15% of baseline. The blood flow for R+UK was 15%∼49%of baseline, while that of US+R+UK was more than 75% of baseline (p<0.001).
Conclusion The combined use of urokinase and glycoprotein IIb/IIIa-targeted microbubbles is effective in targeting thromb and recanalizing thrombolytic occlusion.