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In vivo thrombolysis with targeted microbubbles loading tissue plasminogen activator in a rabbit femoral artery thrombus model

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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 χ2 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.

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Acknowledgments

We wish to thank Dr. Zhaoyang Zhong for professional pathological examination and Prof. Zheng Liu and Prof. Rui Li for expert technical assistance. This work was supported by the National Natural Science Foundation of China [Grant numbers 30500478, 30801060].

Conflict of interest

The authors state that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Ultrasound, Southwest Hospital, Third Military Medical University, Chongqing, China

    Xing Hua, Lina Zhou, Yun He & Qinghai Chen

  2. Department of Ultrasound, Xinqiao Hospital, Third Military Medical University, Shapingba, Chongqing, 400037, China

    Ping Liu, Kaibin Tan, Yuejuan Gao & Yunhua Gao

Authors
  1. Xing Hua
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  2. Lina Zhou
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  3. Ping Liu
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  4. Yun He
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  6. Qinghai Chen
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  7. Yuejuan Gao
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  8. Yunhua Gao
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Correspondence to Yunhua Gao.

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Hua, X., Zhou, L., Liu, P. et al. In vivo thrombolysis with targeted microbubbles loading tissue plasminogen activator in a rabbit femoral artery thrombus model. J Thromb Thrombolysis 38, 57–64 (2014). https://doi.org/10.1007/s11239-014-1071-8

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  • DOI: https://doi.org/10.1007/s11239-014-1071-8

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