Thrombolysis effect of a novel targeted microbubble with low-frequency ultrasound in vivo

Bing Wang; Li Wang; Xiao-Bo Zhou; Ya-Min Liu; Mei Wang; Hao Qin; Chong-Bao Wang; Ju Liu; Xiao-Jiang Yu; Wei-Jin Zang

doi:10.1160/TH07-09-0583

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 100(02): 356-361
DOI: 10.1160/TH07-09-0583

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

Thrombolysis effect of a novel targeted microbubble with low-frequency ultrasound in vivo

Authors

Bing Wang

¹Department of Pathology, School of Medicine, Xi’an Jiaotong University, Xi’an Shaanxi, P. R. China
Li Wang

²Department of Pharmacology, School of Medicine, Xi’an Jiaotong University, Xi’an Shaanxi, P. R. China
Xiao-Bo Zhou

³Department of Immunology, School of Medicine, Xi’an Jiaotong University, Xi’an Shaanxi, P. R. China
Ya-Min Liu

⁴Peripheral Ve ssels Department of the First Hospital, Xi’an Jiaotong University, Xi’an Shaanxi, P. R. China
Mei Wang

⁵Department of Dermatology of the Second Hospital, Xi’an Jiaotong University, Xi’an Shaanxi, P. R. China
Hao Qin

⁴Peripheral Ve ssels Department of the First Hospital, Xi’an Jiaotong University, Xi’an Shaanxi, P. R. China
Chong-Bao Wang

⁴Peripheral Ve ssels Department of the First Hospital, Xi’an Jiaotong University, Xi’an Shaanxi, P. R. China
Ju Liu

⁶Department of Intervention of the First Hospital of Xi’an, Xi’an Shaanxi, P.R. China
Xiao-Jiang Yu

²Department of Pharmacology, School of Medicine, Xi’an Jiaotong University, Xi’an Shaanxi, P. R. China
Wei-Jin Zang

²Department of Pharmacology, School of Medicine, Xi’an Jiaotong University, Xi’an Shaanxi, P. R. China

⁷Key Laboratory of Environment and Genes Related to Diseases of the Ministry of Education, Xi’an Jiaotong University, Xi’an Shaanxi, P. R. China

Abstract

Summary

Clot-targeted microbubbles (TMB) were developed based on oligopeptide specific to the glycoprotein IIb/IIIa receptor on active platelets. In this study, we aimed to elucidate the thrombolysis effect of this TMB in both intraarterial and intravenous application and compare the clot lysis efficiency of the TMB and untargeted microbubbles(UTMB) in presence of external low frequency ultrasound (LFUS) (800kHz, 2.4w/cm², pulse-wave). An acute arterial occlusion model was induced in rabbits by blocking the common carotid artery with an autogenous clot. Animals were randomized to five groups to receive the following treatment: 1) intra-arterial TMB and LFUS (IA TMB/LFUS); 2) intravenous TMB and LFUS (IV TMB/LFUS); 3) intravenous untargeted-microbubbles and LFUS (IV UTMB/LFUS);4) LFUS only; 5) intra-arterial normal saline (NS) control. Declotting score and a variation of thrombolysis-in-myocardial-infarction (TIMI) flow scale were applied to assess clot clearance and flow restore according to the angiogram. IA TMB/LFUS treatment produced highest declotting score (3.5 ± 0.53) and success rate (100%).IV TMB/LFUS treatment produced a higher declotting score (1.95 ± 1.12) than LFUS treatment (0.53 ± 0.38) (P=0.026).and higher TIMI (1.94 ± 0.62 vs.0.47 ± 0.44, P=0.020).When administrated intravenously, TMB/LFUS created a higher declotting score (1.95 ± 1.12) than that of UTMB/LFUS (0.61 ± 0.43) (P=0.033).The superiority was observed in TIMI also (1.94 ± 0.62 vs.0.72 ± 0.25, P=0.041).The results demonstrate that either intra-arterial or intravenous TMB is effective in clearing clot in-vivo model. The TMB showed advantage over UTMB in systemic administration.

Keywords

Thrombolysis - target - microbubble - ultrasound

Full Text

References

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