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, Inhaltsverzeichnis

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

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

› Institutsangaben

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

Volltext

Referenzen

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