Analysis of flow spectrum change and possible mechanism of using urokinase and glycoprotein IIb/IIIa-targeted microbubbles prepared by direct conjugation method to dissolve the thromb in vivo

Abstract

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 in vivo and analyse the velocity tracing change of blood flow and explore the possible mechanism. Methods A total of 42 rabbits with platelet-rich thrombi in the femoral artery were randomized into 7 treatment groups ( n = 6 in each group): 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 platelet-targeted microbubble ( US + R); 6) platelet-targeted microbubble plus urokinase (R + UK); 7)ultrasound, platelet-targeted microbubble and urokinase (US + R + UK). A total of 6 ml of infusion liquor of Urokinase,RGDS and microbubbles (SonoVue) were mixed by 1 ∶ 1 ∶ 1 ratio by the direct conjugation method, infusion via vein within 20 min. Ultrasound was conducted to lyse the clot for 30 min. The recanalization and the velocity tracing change of blood flow in thrombolytic process were evaluated at 120 min post treatment. Results For US, UK, US + M, US + R and US + M + UK groups, recanalization was failed. The R + UK and US + R + UK was recanalizated ( P ＜0.001 ). The blood flow velocity tracing was small and low width in US,UK, US + M, US + R and US + M + UK groups. The wave was high width and disorderly under the thrombolysis therapy in the R + UK and US + R + UK. The thrombolytic effect was demonstrated by the high-width and disorderly resonance changes in the blood flow spectrum during the thrombolytic therapy of US + R + UK. Conclusions The blood flow spectrum of groups had different characteristics in vivo when thrombus was issolved,ultrasonic resonance might be the possible mechanism. Key words: Ultrasonography; Microbubbles; Thrombolytic therapy; Urinary plasminogen activator; RGDS