Thrombolysis effect of a novel targeted microbubble with low-frequency ultrasound in vivo.
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) (800 kHz, 2.4 w/cm(2), 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.
Wang
Bing
B
Department of Pharmacology, School of Medicine, Xi'an Jiaotong University, Xi'an, PR China.
Wang
Li
L
Zhou
Xiao-Bo
XB
Liu
Ya-Min
YM
Wang
Mei
M
Qin
Hao
H
Wang
Chong-Bao
CB
Liu
Ju
J
Yu
Xiao-Jiang
XJ
Zang
Wei-Jin
WJ
D000208:Acute Disease; D000792:Angiography; D000818:Animals; D017536:Carotid Artery, Common; D004195:Disease Models, Animal; D005263:Femoral Artery; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D045423:Microbubbles; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D011817:Rabbits; D015912:Thrombolytic Therapy / Q000295:instrumentation* / Q000379:methods*; D013927:Thrombosis / Q000000981:diagnostic imaging* / Q000628:therapy*; D018084:Ultrasonography, Interventional
D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D005340:Fibrinogen