Low-intensity focused ultrasound guided dodecafluoropentane-loaded acoustic phase-change nanoparticles for treatment of porcine coronary microthromboembolism

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.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.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).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.