低强度聚焦超声引导负载十二氟戊烷的声学相变纳米颗粒治疗猪冠状动脉微血栓栓塞症
Low-intensity focused ultrasound guided dodecafluoropentane-loaded acoustic phase-change nanoparticles for treatment of porcine coronary microthromboembolism.
作者信息
Jiang Nan, Wang Zhiwen, Deng Qing, Zhou Yanxiang, Cao Sheng, Zhou Qing, Chen Jinling, Guo Ruiqiang, Hu Bo
机构信息
Echo Lab, Department of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Echo Lab, Department of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan 430060, China.
出版信息
Int J Cardiol. 2023 Jan 15;371:1-9. doi: 10.1016/j.ijcard.2022.09.078. Epub 2022 Oct 5.
BACKGROUND
Coronary microthromboembolism after acute myocardial infarction (AMI) requires urgent and effective treatment. Early and effective recovery of coronary microcirculation perfusion for the management of AMI would be crucial for better prognosis. Ultrasound assisted thrombolysis in the in-vitro experiments have great potential for the elimination of acute coronary microthromboembolism, especially with stable cavitation using low-intensity focused ultrasound (LIFU) and dodecafluoropentane-loaded acoustic phase-change nanoparticles (DDFP@NPs). Therefore, our study sought to perform animal experiments using this novel treatment method in a porcine model with acute coronary microthromboembolism for further investigation of potential therapeutic values.
METHODS
Porcine model with acute coronary thromboembolism was established using percutaneous coronary intervention and autologous thrombus injection. For ultrasound assisted thrombolysis, DDFP@NPs were prepared by rotary evaporation and sonication process, and LIFU was optimized. Echocardiography and TTC staining were performed for the evaluation of porcine model establishment and treatment effect.
RESULTS
The treatment using LIFU guided DDFP@NPs had almost completely recanalized culprit coronary branch after treatment procedure, and smaller infarcted size (5.4 ± 1.0%), better LVEF (52.5 ± 1.8%) and better coronary microcirculation after 28 days of treatment, which outperformed treatments using LIFU+SonoVue microbubbles (infarcted size: 26.4 ± 3.5% and LVEF: 37.2 ± 3.1%) and LIFU only (infarcted size: 32.2 ± 3.1% and LVEF: 32.2 ± 0.4%) (all P < 0.05), while the treatment effect were similar to treatment using intravenous tissue-plasminogen activator (infarcted size: 4.9 ± 0.9% and LVEF: 53.1 ± 1.1%) (all P > 0.05).
CONCLUSIONS
Our study has innovatively established a treatment method using DDFP@NPs combined with LIFU irradiation for coronary thrombolysis and verified its treatment effect with high-efficient thrombolysis in the in-vivo experiments, which can be considered as powerful experimental evident of the novel method for potential clinical use of acute coronary thrombolysis. Multidimensional experimental investigations and cautious verification may need before the method could be used as treatment before preliminary clinical trials.
背景
急性心肌梗死（AMI）后的冠状动脉微血栓栓塞需要紧急且有效的治疗。早期有效恢复冠状动脉微循环灌注以管理AMI对于改善预后至关重要。体外实验中的超声辅助溶栓对于消除急性冠状动脉微血栓栓塞具有巨大潜力，尤其是使用低强度聚焦超声（LIFU）和载有十二氟戊烷的声学相变纳米颗粒（DDFP@NPs）产生的稳定空化效应。因此，我们的研究旨在使用这种新型治疗方法在急性冠状动脉微血栓栓塞的猪模型中进行动物实验，以进一步研究其潜在的治疗价值。
方法
采用经皮冠状动脉介入和自体血栓注射建立猪急性冠状动脉血栓栓塞模型。对于超声辅助溶栓，通过旋转蒸发和超声处理制备DDFP@NPs，并优化LIFU。进行超声心动图和TTC染色以评估猪模型的建立和治疗效果。
结果
使用LIFU引导DDFP@NPs的治疗在治疗后几乎完全再通了罪犯冠状动脉分支，治疗28天后梗死面积较小（5.4±1.0%），左心室射血分数（LVEF）较好（52.5±1.8%），冠状动脉微循环较好，优于使用LIFU+声诺维微泡的治疗（梗死面积：26.4±3.5%，LVEF：37.2±3.1%）和仅使用LIFU的治疗（梗死面积：32.2±3.1%，LVEF：32.2±0.4%）（均P<0.05），而治疗效果与使用静脉组织纤溶酶原激活剂的治疗相似（梗死面积：4.9±0.9%，LVEF：53.1±1.1%）（均P>0.05）。
结论
我们的研究创新性地建立了一种使用DDFP@NPs联合LIFU照射进行冠状动脉溶栓的治疗方法，并在体内实验中验证了其高效溶栓的治疗效果，这可被视为该新方法用于急性冠状动脉溶栓潜在临床应用的有力实验证据。在该方法可用于初步临床试验前的治疗之前，可能需要进行多维度的实验研究和谨慎验证。
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