The ultrasound contrast imaging properties of lipid microbubbles loaded with urokinase in dog livers and their thrombolytic effects when combined with low-frequency ultrasound in vitro

• Published in: Journal of thrombosis and thrombolysis Vol. 37; no. 3; pp. 303 - 309
• Main Authors: Ren, Shu-Ting, Kang, Xiao-Ning, Liao, Yi-Ran, Wang, Wei, Ai, Hong, Chen, Li-Na, Luo, Hui-Ting, Fu, Rong-Guo, Tan, Li-Fang, Shen, Xin-Liang, Wang, Bing
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.04.2014; Springer Nature B.V
• Subjects: Animals; Cardiology; Contrast Media - pharmacology; Dogs; Fibrinolytic Agents - therapeutic use; Hematology; Liver - blood supply; Liver - ultrastructure; Medicine; Medicine & Public Health; Microbubbles; Thrombolytic Therapy - instrumentation; Thrombolytic Therapy - methods; Thrombosis - diagnostic imaging; Thrombosis - therapy; Ultrasonography - instrumentation; Ultrasonography - methods; Urokinase-Type Plasminogen Activator - therapeutic use; Urokinase; Microbubble; Thrombolysis; Ultrasound contrast imaging
• ISSN: 0929-5305; 1573-742X; 1573-742X
• DOI: 10.1007/s11239-013-0950-8

A new microbubble loaded with urokinase (uPA-MB) was explored in a previous study. However, its zeta potential and ultrasound contrast imaging properties and its thrombolytic effects when combined with low-frequency ultrasound (LFUS) were unclear. The zeta potential and ultrasound contrast imaging property of 5 uPA-MBs loading with 50,000 IU uPA was respectively detected using a Malvern laser particle analyzer and a Logiq 9 digital premium ultrasound system. Its ultrasound contrast imaging property was performed on the livers of two healthy dogs to compare with SonoVue. And the clot mass loss rate, D-dimer concentration and surface morphology of the clot residues were measured to evaluate the thrombolytic effect after treatment with three doses of 5 uPA-MBs combined with LFUS in vitro. The zeta potential of 5 uPA-MBs (−27.0 ± 2.40 mV) was higher than that of normal microbubbles (−36.95 ± 1.77 mV). Contrast-enhanced imaging of the hepatic vessels using 5 uPA-MBs was similar to SonoVue, while the imaging duration of 5 uPA-MBs (10 min) was longer than SonoVue (6 min). The thrombolytic effect of three doses of uPA-MBs combined with LFUS was significantly better than that of the control group and showed dose dependence. The 5 uPA-MBs have a negative charge on their surface and good echogenicity as ultrasound contrast agents. The 5 uPA-MBs combined with LFUS can promote thrombolysis in a dose-dependent manner.