title: In vivo thrombolysis with targeted microbubbles loading tissue plasminogen activator in a rabbit femoral artery thrombus model.
abstract: The increasingly high incidence of ischemic stroke caused by thrombosis of the arterial vessels is one of the major factors that threaten people's health and lives in the world. The present treatments for thrombosis are unsatisfactory yet. We developed the microbubbles loading tissue plasminogen activator (tPA) and their in vitro thrombolysis efficacy under ultrasound exposure has been proved previously. We tried to investigate their thrombolysis effect in vivo in this present study. Thrombus model was made by clamping bilateral femoral arteries in 70 arteries of 40 rabbits. The targeted tPA-loaded microbubbles were made by lyophilization, taking arginine-glycine-aspartic acid-serine peptide as the targeting ligand. Its thrombolysis efficacy, calculated as count rate and efficiency rate of recanalization, was evaluated by Pearson's χ(2) and One-way ANOVA, respectively. The count rate of recanalization of the targeted tPA-loaded microbubbles under ultrasound exposure (70%) was similar to that of the combination of tPA, microbubbles and ultrasound exposure (80%) (P = 0.61), while its tPA dosage (0.06 mg/kg) was much less than that of latter (0.9 mg/kg). Its efficiency rate of recanalization was the highest among all groups (53.22 ± 40.39%) (P < 0.01). Ultrasound-induced targeted tPA-loaded microbubbles release is a promising thrombolytic method with satisfactory thrombolytic efficacy, lowered tPA dose and potentially decreased hemorrhagic risk.
authors.affiliation: Department of Ultrasound, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Hua
authors.forename: Lina
authors.initials: L
authors.lastname: Zhou
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Yun
authors.initials: Y
authors.lastname: He
authors.forename: Kaibin
authors.initials: K
authors.lastname: Tan
authors.forename: Qinghai
authors.initials: Q
authors.lastname: Chen
authors.forename: Yuejuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D045423:Microbubbles / Q000627:therapeutic use*; D011817:Rabbits; D015912:Thrombolytic Therapy / Q000379:methods*; D013927:Thrombosis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*; D014463:Ultrasonography
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator