A Novel Ultrasound Microbubble Contrast Agent:Application For Ultrasound Image Enhancement And Therapy For Arteriovenous Thrombosis

Objective:The experiment was designed to investigate a novel lipidic microbubble wrapped with L-arginine(L-Arg)targeting to P-selectin enhances the ultrasound image of thrombus and reduces the volume of arteriovenous thrombosis in its early stages in a rat model.Methods:Putting the fresh cubital vein blood clots made by centrifugal in the extracorporeal circulation model to observe the effect of targeted ultrasound contrast agent for ultrasound image in vitro.In vivo experiments includes two parts—arterial thrombosis and deep vein thrombosis(DVT).Arterial thrombosis was induced by covering a ferric-chlLoride(FeC13)-filter paper on abdominal aorta(AA)and DVT was induced by ligation of the left common iliac vein(LCIV)in a rat model.The rats were sacrificed after 24 hours after thrombosis.L-Arg was warpped in the P-selectin-targeted microbubbles which were injected(1ml/kg)via tail vein before model establishment.Thrombi isolated from LCIV and AA were measured by dry weight and length.The coagulation functions including prothrombin time(PT),thrombin time(TT),activated partial thromboplastin time(APTT),and fibrinogen(FIB)were tested as well.Results:After incubated with this novel microbubbles,the ultrasound image of thrombus significantly enhanced.The dry weight and length of the thrombi isolated form LCIV and AA also significantly decreased in novel microbubbles group.There were no statistical difference among the groups in terms of PT,APTT,TT and FIB.Conclusion:This novel microbubble ultrasound contrast agent can enhance the image of thrombus and decrease the weight and length in the early stages of thrombosis may because of its two significant characteristics.First,its target is P-selectin which may be exposured on the surface of platelets and endothelial cells by the activations of plateles and impaired endothelium.Second,the L-Arg wrapped in the microbubble is the substrate for endogenous synthesis of nitric oxide(NO)which could reduce platelets and inflammatory cells aggregation.