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DOI: 10.1160/TH07-09-0583
Thrombolysis effect of a novel targeted microbubble with low-frequency ultrasound in vivo
Financial support: This study was supported by the National 863 Plan (No. 2006AA02Z4A5), the National Basic Research Program of China (973 Program No. 2007CB512005), the National Natural Science Foundation (Nos. 30300325 and 30770785), Province Natural Science Foundation (Nos. 2002K10-G6–07, 2003k10-G10(1) and 2004C201), the Chinese Biomedical Foundation of Xi’an City (No. ZX05012), the Province T e chnology Special Foundation (No. 2006kz04-G1),. the National Natural Science Foundation of China (No. 30770785), the Cultivation Fund of the Key Scientific and Technical Innovation Project of Chinese Ministry of Education (No. 705045) and the Specialized Research Fund for the Doctoral Program of Higher Education (No.20050698012).Publication History
Received
26 September 2007
Accepted after major revision:
02 June 2008
Publication Date:
22 November 2017 (online)


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.