PB0014 - Pulsed- high intensity focused ultrasound- based microbubble- mediated sonothrombolytic therapy accompanied by tPA administration reduce thrombus content in the arterial atherothrombotic stenosis

Background: Vascular disease arises through the complications of atherosclerosis, a complex chronic inflammatory condition affecting the arterial circulation. It leads to the development of vascular lesions or atherosclerotic plaques, which manifest as asymmetrical thickenings of the intima of medium to large sized elastic and muscular arteries. Arterial thrombosis on ruptured atherosclerotic plaques can lead to acute events, such as myocardial infarction and ischemic stroke.

Aims: The aim of this study was to generate a rabbit model of common carotid artery atherothrombotic stenosis and the subsequent investigating the feasibility of combined microbubbles- mediated sonothrombolytic therapy plus tissue plasminogen activator (tPA) administration in this model.

Methods: Briefly, New Zealand white rabbits were submitted to common carotid artery atherothrombotic stenosis by primary balloon injury followed 1.5% cholesterol- rich diet injury for 12 weeks and finally perivascular severe cold injury. Then treatment group underwent combined pulsed- high intensity focused ultrasound (130 W/cm2, PD= 25 ms F= 750 MHz)- based microbubble- mediated sonothrombolytic therapy plus tPA (0.6 mg/kg) administration.

Results: Results from histopathology, B-mode and color Doppler ultrasonography, showed a significant reduction in the mean value for thrombus content, blood mean velocity and a significant increase in the mean value for blood volume flow at the stenotic region in the treatment group compared with the other groups (P < 0.05).

Conclusion(s): Enhanced anti- thrombotic effect of tPA, due to sonoporation effect of ultrasound, accompanied by enhanced Sonothrombolysis effect of pulsed ultrasound (Cavitation Microjet, Cavitation Microstreaming, Cavitation Shock Waves)- induced by collapsed microbubbles, can cause to reduce the thrombus content and significantly dilate the luminal cross-sectional area of stenosis and lower treatment time in comparison with conventional tPA thrombolytic therapy.