Thrombolytic effects of a combined therapy with targeted microbubbles and ultrasound in a 6 h cerebral thrombosis rabbit model.

Abstract

Our previous study has shown that P1 polypeptide-loaded microbubbles (clot-targeted microbubbles, TMB) are effective for thrombolysis and recanalization in a 0.5 h cerebral thrombosis rabbit model when combined with low-frequency ultrasound (LFUS, 0.8 MHz). However, the thrombolytic effects of TMB combined with LFUS are still unclear in a 6 h cerebral thrombosis rabbit model, which closely resembles human embolic stroke. Aiming to extend the 3 h therapeutic window limitation of thrombolytic drugs, a 6 h cerebral thrombosis model of common carotid artery (CCA) occlusion was induced in rabbits, and thrombolysis using TMB by intra-arterial (IA) and intravenous (IV) application combined with LFUS was then compared to untargeted microbubbles (UTMB) and recombinant tissue plasminogen activator (rt-PA). The patency score and thrombolysis in brain ischemia (TIBI) in IA TMB combined with LFUS (IA TMB/LFUS) were significantly higher compared to the IA normal saline control with LFUS (IA SC/LFUS) (both P < 0.05) and IA UTMB plus LFUS (IA UTMB/LFUS) (both P < 0.05), respectively. The recanalization rate in the IA TMB/LFUS group (66.67%) was significantly higher compared to the IA SC/LFUS group (12.50%, P < 0.05). The patency score, TIBI and recanalization rate of IA TMB/LFUS were higher than in the IV TMB/LFUS group, but there was no significant difference between the two groups, which was similar to the infarction ratio. TMB/LFUS is an effective and safe therapy for thrombolysis in a 6 h cerebral thrombosis rabbit model, and the IA TMB/LFUS group was slightly better than the IV TMB/LFUS group.

• Authors: Shu-Ting Ren, Li-Hui Long, Mei Wang, Yi-Ping Li, Hao Qin, Hui Zhang, Bo-Bin Jing, Ying-Xue Li, Wei-Jin Zang, Bing Wang, Xin-Liang Shen
• Journal: Journal of thrombosis and thrombolysis (J Thromb Thrombolysis) Vol. 33 Issue 1 Pg. 74-81 (Jan 2012) ISSN: 1573-742X [Electronic] Netherlands
• PMID: 22016106 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fibrinolytic Agents

Topics

• Animals
• Combined Modality Therapy
• Drug Delivery Systems (methods)
• Female
• Fibrinolytic Agents (administration & dosage)
• Intracranial Thrombosis (diagnostic imaging, pathology, therapy)
• Male
• Microbubbles (therapeutic use)
• Rabbits
• Random Allocation
• Thrombolytic Therapy (methods)
• Ultrasonic Therapy (methods)
• Ultrasonography